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Sample records for cancer cells effects

  1. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

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    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)

    2010-11-15

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  2. Growth-stimulatory effect of resveratrol in human cancer cells.

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    Fukui, Masayuki; Yamabe, Noriko; Kang, Ki Sung; Zhu, Bao Ting

    2010-08-01

    Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.

  3. Differential effects of bisphosphonates on breast cancer cell lines

    NARCIS (Netherlands)

    Verdijk, R.; Franke, H.R.; Wolbers, F.; Vermes, I.

    2007-01-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancers cells in virtro. In this study, six bisphosphonates were administered to three breast caner cell lines. Cell proliferation was measured by quantification of th expressio of Cyclin D1 mRNA. Apoptosis was determined by flow cytome

  4. Apoptotic effect of noscapine in breast cancer cell lines.

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    Quisbert-Valenzuela, Edwin O; Calaf, Gloria M

    2016-06-01

    Cancer is a public health problem in the world and breast cancer is the most frequently cancer in women. Approximately 15% of the breast cancers are triple-negative. Apoptosis regulates normal growth, homeostasis, development, embryogenesis and appropriate strategy to treat cancer. Bax is a protein pro-apoptotic enhancer of apoptosis in contrast to Bcl-2 with antiapoptotic properties. Initiator caspase-9 and caspase-8 are features of intrinsic and extrinsic apoptosis pathway, respectively. NF-κB is a transcription factor known to be involved in the initiation and progression of breast cancer. Noscapine, an alkaloid derived from opium is used as antitussive and showed antitumor properties that induced apoptosis in cancer cell lines. The aim of the present study was to determine the apoptotic effect of noscapine in breast cancer cell lines compared to breast normal cell line. Three cell lines were used: i) a control breast cell line MCF-10F; ii) a luminal-like adenocarcinoma triple-positive breast cell line MCF-7; iii) breast cancer triple-negative cell line MDA-MB-231. Our results showed that noscapine had lower toxicity in normal cells and was an effective anticancer agent that induced apoptosis in breast cancer cells because it increases Bax gene and protein expression in three cell lines, while decreases Bcl-xL gene expression, and Bcl-2 protein expression decreased in breast cancer cell lines. Therefore, Bax/Bcl-2 ratio increased in the three cell lines. This drug increased caspase-9 gene expression in breast cancer cell lines and caspase-8 gene expression increased in MCF-10F and MDA-MB-231. Furthermore, it increased cleavage of caspase-8, suggesting that noscapine-induced apoptosis is probably due to the involvement of extrinsic and intrinsic apoptosis pathways. Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced expression, probably due to decrease in NF-κB gene and protein expression

  5. EFFECT OF SOMATOSTATIN ON THE CELL CYCLE OF HUMAN GALLBLADDER CANCER CELL

    Institute of Scientific and Technical Information of China (English)

    李济宇; 全志伟; 张强; 刘建文

    2005-01-01

    Objective To explore the effect of somatostatin on the cell cycle of human gallbladder cancer cell. Methods Growth curve of gallbladder cancer cell was measured after somatostatin treated on gradient concentration. Simultaneously, the change of gallbladder cancer cell cycle was detected using flow cytometry.Results Concentration-dependent cell growth inhibition caused by somatostatin was detected in gallbladder cancer cell(P<0.05). Cell growth was arrested in S phase since 12h after somatostatin treated, which reached its peak at 24h, then fell down. The changes in apoptosis index of gallbladder cancer cell caused by somatostatin correlated with that's in cell cycle. Conclusion Somatostatin could inhibit the cell growth of human gallbladder cancer cell in vitro on higher concentration. It might result from inducing growth arrest in S phase in early stage and inducing apoptosis in the late stage.

  6. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

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    Duan, Lincan [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Shen, Hongmei [Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhao, Guangqiang [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Yang, Runxiang [Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Cai, Xinyi [Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhang, Lijuan [Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Jin, Congguo [Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Huang, Yunchao, E-mail: daliduanlincan@163.com [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  7. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

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    Tiffany M. Phillips

    2007-12-01

    Full Text Available BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs. In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. METHODS: In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR, CD24, CD44, Jagged-1 expression, activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and P13-kinase blocked both effects. CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.

  8. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...

  9. The effects of cyclooxygenase-2 inhibitors on urological cancer cells.

    Science.gov (United States)

    Yoshimura, Rikio; Matsuyama, Masahide; Kawahito, Yutaka; Takemoto, Yoshiaki; Tsuchida, Kenji; Kuratsukuri, Katsuyuki; Segawa, Yoshihiro; Shinnka, Toshiaki; Sano, Hajime; Nakatani, Tatsuya

    2004-06-01

    Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.

  10. Effect of acute exercise on prostate cancer cell growth.

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    Rundqvist, Helene; Augsten, Martin; Strömberg, Anna; Rullman, Eric; Mijwel, Sara; Kharaziha, Pedram; Panaretakis, Theocharis; Gustafsson, Thomas; Östman, Arne

    2013-01-01

    Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  11. Effect of acute exercise on prostate cancer cell growth.

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    Helene Rundqvist

    Full Text Available Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum and after completed exercise (exercise serum. The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  12. Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells

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    Hye-Yeon Han

    2014-01-01

    Full Text Available Background: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. Objective: To investigate the anti-cancer effect of K. scoparia on breast cancer. Materials and Methods: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. Results: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC 50 value of 36.2 μg/ml. MEKS at 25 μg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose polymerase (PARP. Conclusion: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

  13. Proapoptotic effect of endocannabinoids in prostate cancer cells.

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    Orellana-Serradell, O; Poblete, C E; Sanchez, C; Castellón, E A; Gallegos, I; Huidobro, C; Llanos, M N; Contreras, H R

    2015-04-01

    In the early stages, prostate cancer is androgen‑ dependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line and primary cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry where we showed a higher expression of these receptors in later stages of the disease (samples with a high Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT assay, we proved that the treatments produced a cell growth inhibitory effect on all the different prostate cancer cultures. This effect was demonstrated to be dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed that this effect was produced primarily from the activation of the CB1 receptor. In order to understand the MTT assay results, we determined cell cycle distribution by flow cytometry, which showed no variation at the different cell cycle stages in all the cultures after treatment. Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed

  14. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

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    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

  15. In vitro effects of polyphenols on colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Barbara; Pampaloni; Gaia; Palmini; Carmelo; Mavilia; Roberto; Zonefrati; Annalisa; Tanini; Maria; Luisa; Brand

    2014-01-01

    AIM:To investigate the effects of quercetin and genistein on colon cancer cell proliferation and their estrogen receptorβ(ERβ)expression.METHODS:Colon cancer cells were stably transfected with a mammalian expression vector to overexpress ERβ(HCT8-β8-expressing cells)or a control vector(HCT8-pSV2neo-expressing cells).The proliferation of these cells was examined after treatment with quercetin or genistein(5-100μmol/L),or 10 nmol/L17β-estradiol(17β-E2).Cell viability was examined by acridine orange staining following treatments for 48 or144 h.Effects of quercetin and genistein on ERβtranscriptional transactivation were examined by luciferase activity in HCT8-β8-expressing cells transiently transfected with a pEREtkLUC reporter vector.In addition,the regulation of ERβtranscription by phytoestrogens and 17β-E2 was examined by quantitative polymerase chain reaction.RESULTS:Proliferation of HCT8-β8-expressing cells was not reduced low doses(5μmol/L)of quercetin and genistein,while it was reduced at 25-50μmol/L with an effect similar to 10 nmol/L 17β-E2.Treatment with doses of phytoestrogens≥75μmol/L completely blocked cell growth and reduced overall cell counts,however no effects at any dose were observed in HCT8-pSV2neoexpressing cells.These results were supported by viability staining that revealed acridine orange-stained lysosomes with high doses or extended treatment periods.Genistein and quercetin(50μmol/L)significantly increased ER-responsive luciferase activity similar to 10nmol/L 17β-E2(P<0.05).Furthermore,genistein and quercetin(50μmol/L),as well as 10 nmol/L 17β-E2significantly increased ERβmRNA levels in HCT8-β8-expressing cells(P<0.05).In addition,treatment of HCT8-pSV2neo-expressing cells with 50μmol/L quercetin or 10 nmol/L 17β-E2 significantly increased ERβmRNA levels compared to untreated controls(P<0.05),though the absolute levels were much lower than in HCT8-β8-expressing cells.CONCLUSION:The antitumorigenic effects of the

  16. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

    Science.gov (United States)

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  17. Antiproliferative effect of exemestane in lung cancer cells

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    Giannopoulou Efstathia

    2009-01-01

    Full Text Available Abstract Background Recent evidence suggests that estrogen signaling may be involved in the pathogenesis of non-small cell lung cancer (NSCLC. Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In the current study we investigated the activity of the aromatase inhibitor exemestane in human NSCLC cell lines H23 and A549. Results Aromatase expression was detected in both cell lines. H23 cells showed lower protein and mRNA levels of aromatase, compared to A549 cells. Exemestane decreased cell proliferation and increased apoptosis in both cell lines, 48 h after its application, with A549 exhibiting higher sensitivity than H23 cells. Aromatase protein and mRNA levels were not affected by exemestane in A549 cells, whereas an increase in both protein and mRNA levels was observed in H23 cells, 48 h after exemestane application. Moreover, an increase in cAMP levels was found in both cell lines, 15 min after the administration of exemestane. In addition, we studied the effect of exemestane on epidermal growth factor receptor (EGFR localization and activation. Exemestane increased EGFR activation 15 min after its application in H23 cells. Furthermore, we demonstrated a translocation of EGFR from cell membrane, 24 h after the addition of exemestane in H23 cells. No changes in EGFR activation or localization were observed in A549 cells. Conclusion Our findings suggest an antiproliferative effect of exemestane on NSCLC cell lines. Exemestane may be more effective in cells with higher aromatase levels. Further studies are needed to assess the activity of exemestane in NSCLC.

  18. Effect of NS-398 on colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qing Jia; Ning Zhong; Li-Hui Han; Jing-Hua Wang; Ming Yan; Fan-Li Meng; Shang-Zhong Zhang

    2005-01-01

    AIM: To study the effect of NS-398, a selective cyclooxygenase2 (COX-2) inhibitor, on invasion of colon cancer cell line HT-29 in vitro and to explore its mechanisms.METHODS: Invasive behaviors of the malignant colon cancer cell line HT-29 were investigated in this study.Expressions of COX-2 and CD44v6 in HT-29 cells were detected by flow cytometry. Cellular survival rate was determined by MTT assay. The invasive capacity was quantified by a modified Boyden chamber model. Alterations of cytoskeleton component F-actin were observed by confocal laser scanning microscope.RESULTS: Flow cytometry analysis showed that COX-2was highly expressed in HT-29 cells. The invasive capability of HT-29 cells could be greatly inhibited by NS-398 at the experimental concentrations of 0.1, 1.0 and 10 μmol/L with an inhibitory rate of 22.74%, 42.35% and 58.61% (P<0.01),respectively. MTT assay showed that NS-398 at the experimental concentrations had no significant influence on cellular viability, indicating that such anti-invasive effects had no relationship with cytotoxicity. F-actin was mainly distributed around nuclei forming annular structure in HT-29cells. After exposure to NS-398 of 10 μmol/L, the annular structure around nuclei disappeared and the fluorescence intensity of F-actin decreased obviously. Treatment with NS-398 could down-regulate the expression of CD44v6 as well.CONCLUSION: NS-398 has anti-invasive effects on colon cancer HT-29 cells in vitro, which may be mediated by a novel mechanism of disruption of cytoskeleton. Downregulation of CD44v6 expression may be related to alterations of cytoskeleton.

  19. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    OpenAIRE

    Hu, Wei-Min; Li, Li; Jing, Bao-Qian; Zhao, Yong-Sheng; Wang, Chao-Li; Feng, Li; Xie, Yong-En

    2010-01-01

    AIM: To investigate the sphingosine 1-phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells.

  20. The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells.

    Science.gov (United States)

    Qin, Jian; Liu, Min; Ding, Qianshan; Ji, Xiang; Hao, Yarong; Wu, Xiaomin; Xiong, Jie

    2014-10-01

    Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.

  1. Effect of staurosporine on cycle of human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Min-Wen Ha; Ke-Zuo Hou; Yun-Peng Liu; Yuan Yuan

    2004-01-01

    AIM: To study the effect of staurosporine (ST) on the cell cycle of human gastriccancer cell lines MGC803 and SGC7901.METHODS: Cell proliferation was evaluated by trypan blue dye exclusion method. Apoptotic morphology was observed under a transmission electron microscope. Changes of cell cycle and apoptotic peaks of cells were determined by flow cytometry. Expression of p21WAFI gene was examined using immunohistochemistry and RT-PCR.RESULTS: The growth of MGC803 and SGC7901 cells was inhibited by ST. The inhibitory concentrations against 50% cells (IC50) at 24 h and 48 h were 54 ng/ml and 23 ng/ml for MlGC803, and 61 ng/ml and 37 ng/ml for SGC7901. Typical apoptotic bodies and apoptotic peaks were observed 24 hafter cells were treated wth ST at a concentration of 200ng/ml. The percentage of cells at G0/G1 phase was decreased and that of cells at G2/M was increased significantly in the group treated wth ST at the concentrations of 40ng/ml,60 ng/ml, 100 ng/ml for 24 h, compared with the control group (P<0.01). The expression levels of p21WAFI gene in both MGC803 and SGC7901 cells were markedly up-regulated after treatment with ST.CONCLUSION: ST can cause arrest of gastric cancer cells at G2/M phase, which may be one of the mechanisms that inhibit cell proliferation and cause apoptosis in these cells.Effect of ST on cells at G2/M phase may be attributed to the up-regulattion of p21WAFI gene.

  2. EFFECTS OF ALGAL COMPOUNDS ON CANCER CELL LINE

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    Anusheel Varshney

    2013-11-01

    Full Text Available Algae are a large group of simple and autotrophic organisms. These organisms do not have well organized cell characteristics like plants, but they are widely used because of their special biological activities. They are considered one of the richest sources of bio medically useful compounds with a large number of therapeutic applications. One of its applications is found to be in treating cancer. Cancer, being a remarkably fatal disease, needs special attention in treatment, and algae is found potent enough in its treatment. This review generates an idea of some compounds which are found in alg ae and are capable enough in displaying anti - cancer properties. This review contains the expected and experimentally found mechanisms and mode of action of several compounds like fucoidan, coibamide A, apratoxin A, curacin A, largazole, cryptophycin 1, sym plostatin and dolastatin 10 and many more which are isolated from different species of algae and exhibit their potential against cancer. Though, many anticancer drugs are in clinical and pre - clinical trials, the review can help to have an idea for further detailed studies and research on these compounds to get an effective drug against cancer.

  3. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Science.gov (United States)

    Mouhieddine, Tarek H.; Nokkari, Amaly; Itani, Muhieddine M.; Chamaa, Farah; Bahmad, Hisham; Monzer, Alissar; El-Merahbi, Rabih; Daoud, Georges; Eid, Assaad; Kobeissy, Firas H.; Abou-Kheir, Wassim

    2015-01-01

    Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK) pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs) are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a) were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) cell lines. Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU) of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence. PMID:26635517

  4. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  5. Pleiotropic effects of cancer cells' secreted factors on human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Al-toub, Mashael; Almusa, Abdulaziz; Almajed, Mohammed

    2013-01-01

    INTRODUCTION: Studying cancer tumors' microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor...... cells' secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. METHODS: Morphological changes were assessed using fluorescence microscopy....... Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring 12.1 and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using a transwell migration system. SB-431542, PF-573228 and PD98059 were used to inhibit transforming...

  6. In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells

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    Subramaniyan Bharathiraja

    2016-11-01

    Full Text Available C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy.

  7. Furanodiene enhances the anti-cancer effects of doxorubicin on ERα-negative breast cancer cells in vitro.

    Science.gov (United States)

    Zhong, Zhang-Feng; Qiang, Wen-An; Wang, Chun-Ming; Tan, Wen; Wang, Yi-Tao

    2016-03-05

    Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anti-cancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ERα-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ERα protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ERα-positive MCF-7 cells. Actually, ERα-knockdown cells were more sensitive than ERα positive cells to furanodiene on the cytotoxicity effect. So the anti-cancer effects of furanodiene and non-steroidal agent in breast cancer cells still requires further investigation. Our results showed that furanodiene exposure could enhance growth inhibitory effects of doxorubicin in ERα-negative MDA-MB-231 cells and ERα-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ERα-positive breast cancer cells, non-tumorigenic breast epithelial cells, macrophage cells, hepatocytes cells, pheochromocytoma cells and cardiac myoblasts cells. Furanodiene enhances the anti-cancer effects of doxorubicin in ERα-negative breast cancer cells through suppressing cell viability via inducing apoptosis in mitochondria-caspases-dependent and reactive oxygen species-independent manners. These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future.

  8. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells

    Science.gov (United States)

    Pellegrini, Paola; Dyczynski, Matheus; Sbrana, Francesca Vittoria; Karlgren, Maria; Buoncervello, Maria; Hägg-Olofsson, Maria; Ma, Ran; Hartman, Johan; Bajalica-Lagercrantz, Svetlana; Grander, Dan; Kharaziha, Pedram; De Milito, Angelo

    2016-01-01

    Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits. PMID:27248168

  9. The Biological Effects of Dickkopf1 on Small Cell Lung Cancer Cells and Bone Metastasis.

    Science.gov (United States)

    Pang, Hailin; Ma, Ningqiang; Jiao, Mi; Shen, Weiwei; Xin, Bo; Wang, Tongfei; Zhang, Feng; Liu, Lili; Zhang, Helong

    2017-01-02

    The bone is among the most common sites of metastasis in patients with lung cancer. Over 30%-40% of lung cancers can develop bone metastasis, and no effective therapeutic methods exist in clinic cases. Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferentially metastasizes to the skeleton. However, the role of DKK1 in osteotropism of small cell lung cancer (SCLC) remains to be elucidated. This study aimed to define the role of DKK1 in SCLC bone metastasis and investigate the underlying mechanisms. Our results demonstrated that the expression level of DKK1 was dramatically higher in bone metastatic SCLC cells (SBC-5 cell line) compared with that in cells without bone metastatic ability (SBC-3 cell line). Therefore, we hypothesized that DKK1 was involved in the bone metastasis of SCLC. We then suppressed the DKK1 expression in SBC-5 cells by RNAi and found that downregulation of DKK1 can inhibit cell proliferation, colony formation, cell migration, and invasion, but increase the apoptosis rate. Downregulation of DKK1 did not affect the cell cycle progression of SBC-5 cells in vitro. In vivo, downregulated DKK1 in SBC-5 cells resulted in attenuated bone metastasis. These results indicated that DKK1 may be an important regulator in bone metastases of SCLC, and targeting DKK1 may be an effective method to prevent and treat skeleton metastases in SCLC cases.

  10. The Warburg effect and mitochondrial stability in cancer cells.

    Science.gov (United States)

    Gogvadze, Vladimir; Zhivotovsky, Boris; Orrenius, Sten

    2010-02-01

    The last decade has witnessed a renaissance of Otto Warburg's fundamental hypothesis, which he put forward more than 80 years ago, that mitochondrial malfunction and subsequent stimulation of cellular glucose utilization lead to the development of cancer. Since most tumor cells demonstrate a remarkable resistance to drugs that kill non-malignant cells, the question has arisen whether such resistance might be a consequence of the abnormalities in tumor mitochondria predicted by Warburg. The present review discusses potential mechanisms underlying the upregulation of glycolysis and silencing of mitochondrial activity in cancer cells, and how pharmaceutical intervention in cellular energy metabolism might make tumor cells more susceptible to anti-cancer treatment.

  11. Effects of ARHI on cell cycle progression and apoptosis levels of breast cancer cells.

    Science.gov (United States)

    Li, Ying; Shi, Li; Han, Chun; Wang, Yishang; Yang, Junlan; Cao, Cheng; Jiao, Shunchang

    2012-10-01

    The purposes of this study were to investigate the role of Aplysia Ras Homolog I (ARHI) on cell growth, proliferation, apoptosis, and other biological characteristics of HER2-positive breast cancer cells. Our goal was to provide experimental evidence for the development of future effective treatments of HER2-positive breast cancer. A pcDNA3.1-ARHI eukaryotic expression vector was constructed and transfected into the human HER2-positive breast cancer cell lines SK-BR-3 and JIMT-1. Then, various experimental methods were utilized to analyze the biological characteristics of ARHI-expressing breast cancer cells and to examine the impact of expression of the ARHI gene on cyclin D1, p27(Kip1), and calpain1 expression. We further analyzed the cells in each group after treatment with trastuzumab to examine the effects of this drug on various cellular characteristics. When we compared pcDNA3.1-ARHI-expressing SK-BR-3 and JIMT-1 cells to their respective empty vector and control groups, we found that cell viability was significantly lower (p SK-BR-3 cells, trastuzumab treatment significantly decreased cell growth (p SK-BR-3 cells and JIMT-1 cells, while it promoted p27(Kip1) and calpain1 expression in these cells. ARHI expression inhibits the growth and proliferation of HER2-positive breast cancer cells, while it also promotes apoptosis in these cells. ARHI expression also improves the sensitivity of JIMT-1 cells to trastuzumab by inducing apoptosis.

  12. Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility

    Science.gov (United States)

    Ramos, R. A.; Zapata, Jair; Condat, C. A.; Deisboeck, Thomas S.

    2013-05-01

    A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor-immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact.

  13. The enhanced effect of lupeol on the destruction of gastric cancer cells by NK cells.

    Science.gov (United States)

    Wu, Xiao-Ting; Liu, Jun-Quan; Lu, Xiao-Ting; Chen, Fu-Xing; Zhou, Zhong-Hai; Wang, Tao; Zhu, Sheng-Ping; Fei, Su-Juan

    2013-06-01

    Lupeol, a triterpene, was reported to possess beneficial effects as a therapeutic and preventive agent for a range of disorders. Many studies have confirmed that lupeol possesses strong activities such as antioxidative, antiinflammatory, antiarthritic, antimutagenic, and antimalarial, both in vitro and in vivo, and at its effective therapeutic doses exhibit no toxicity to normal cells and tissues. Lupeol was observed to inhibit the proliferation of gastric tumour cells in a dose-dependent manner, as assessed by MTT assay, and induce the proliferation of NK cells, as assessed by flow cytometry and Western blotting. The killing effect of NK cells on gastric tumour cells was assessed by LDH. Our experiment demonstrated that lupeol at appropriate concentrations could promote the proliferation of NK cells, inhibit the proliferation of gastric cancer cell lines BGC823, N87 and HGC27, and increase the killing effect of NK cells on gastric cancer cells. We speculated that lupeol might increase the expression of PFP, IFN-γ, and CD107a via the activation of PI3K/Akt and Wnt/β-catenin signalling pathways. Lupeol could serve as a potential agent against gastric cancer; however, further in-depth in vivo studies are still required.

  14. Effects of Src on Proliferation and Invasion of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rui ZHENG

    2011-04-01

    Full Text Available Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells in vitro, respectively. Results pp60src was expressed in all lung cancer cell lines in this study. All 5 non-small cell lung cancer (NSCLC cell lines had increased autophosphorylated tyrosine-418, while nearly no phosphorylated Src in small cell lung cancer SBC5 cell line was detected. The effect of inhibition of Src tyrosine kinase on cell proliferation varied among the lung cancer cell lines. Submicromolar Src tyrosine kinase inhibitor (≤1 μM remarkably suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner (P < 0.05, while the same concentration of Src tyrosine kinase inhibitor had no significant effect on proliferation of H226, PC14PE6 and RERFLCOK cells. Invasiveness of lung cancer cells was significantly suppressed by Src tyrosine kinase in a dose-dependent manner (P < 0.05. Conclusion Phosphorylation of Src, but not over-expression, plays a pivotal role in proliferation and invasion of NSCLC cell lines in vitro.

  15. Fluorescence-based co-culture of normal and cancerous cells as an indicator of therapeutic effects in cancer.

    Science.gov (United States)

    Tamura, Masato; Matsui, Hirofumi; Hyodo, Ichinosuke; Tanaka, Junko; Miwa, Yoshihiro

    2014-10-15

    Comprehensive evaluation of the effects of cancer therapies in vitro is difficult because of the need to distinguish the main effects from the side effects within the data. This problem cannot be overcome by methods involving monoculture, because the effects of anti-cancer drugs in a monoculture can only be measured on either normal or cancerous cells in isolation. In order to promote therapeutic development, therefore, we need a novel drug evaluation method which can simultaneously determine both therapeutic activity and toxicity under a co-culture of normal and cancerous cells. Co-culture creates a more biomimetic condition in comparison to monoculture. The novel method proposed in this study uses an easy experiment for estimating the effects of treatments with various kinds of drugs as a solution to the abovementioned problems. We have previously established two cell lines: a rat gastric mucosal cell line (RGM) and its corresponding cancerous mutant cell line (RGK). In this study, we have developed a new evaluation procedure using a co-culture of green fluorescent protein-expressing RGM cells (RGM-GFP) and kusabira orange-expressing RGK cells (RGK-KO). These cell lines emit green and red fluorescence, respectively. We demonstrated the capability of the method in evaluations of the cancer-selective effects of anti-cancer drugs and X-ray treatment. These results clearly distinguished the cancer-selective toxicity of the applied therapies.

  16. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Directory of Open Access Journals (Sweden)

    Shekoufeh Atashpour

    2015-07-01

    Conclusion:The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.

  17. Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment.

    Science.gov (United States)

    Wang, Jia; Xia, Shi'an; Zhu, Zhizhen

    2015-03-01

    Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is more potent than metformin. However its potential application as a anti-cancer regent is far behind metformin. In order to investigate any beneficial effect of combination of Phenformin and radiotherapy, non-small cell lung cancer cell lines A549 and H1299 were exposure under different dose of ionizing radiation with or without Phenformin. Results indicated Phenformin showed synergistic effect and could induce more cancer cell apoptosis and inhibition of tumor growth compared with ionizing radiation alone. Furthermore, this synergistic effect may be through different pathway according to cancer cell genotype background. Our results showed Phenformin induced AMPK activation in A549 but not H1299. However, Phenformin activated eIF2α in both cell lines. Our findings implicated Phenformin may be used as radiosensitizer for non-small cell lung cancer therapy.

  18. Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7 cells.

    Science.gov (United States)

    Siao, An-Ci; Hou, Chien-Wei; Kao, Yung-Hsi; Jeng, Kee-Ching

    2015-01-01

    Dietary prevention has been known to reduce breast cancer risk. Sesamin is one of the major components in sesame seeds and has been widely studied and proven to have anti-proliferation and anti-angiogenic effects on cancer cells. In this study, the influence of sesamin was tested in the human breast cancer MCF-7 cell line for cell viability (MTT assay) and cell cycling (flow cytometry). Results showed that sesamin dose-dependently (1, 10 and 50 μM) reduced the cell viability and increased LDH release and apoptosis (TUNEL assay). In addition, there was a significant increase of sub-G1 phase arrest in the cell cycle after sesamin treatment. Furthermore, sesamin increased the expression of apoptotic markers of Bax, caspase-3, and cell cycle control proteins, p53 and checkpoint kinase 2. Taken together, these results suggested that sesamin might be used as a dietary supplement for prevention of breast cancer by modulating apoptotic signal pathways and inhibiting tumor cell growth.

  19. The regulatory effects of radiation and histone deacetylase inhibitor on liver cancer cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Ho; Choi, Hyung Seok; Jang, Dong Gun; Lee, Hong Je; Yang, Seoung Oh [Dept. Nuclear Medicine, Dongnam Institute of Radiological and Medicine Sciences Cancer Center, Busan (Korea, Republic of)

    2013-11-15

    Radiation has been an effective tool for treating cancer for a long time. Radiation therapy induces DNA damage within cancer cells and destroys their ability to reproduce. Radiation therapy is often combined with other treatments, like surgery and chemotherapy. Here, we describe the effects of radiation and histone deacetylase inhibitor, Trichostain A, on cell cycle regulation in hepatoma cells. Results demonstrate that the treatment of radiation TSA induces cell cycle arrest, thereby stimulating cell death in hepatoma cells. In addition, since different cells or tissues have different reactivity to radiation and TSA, these results might be an indicator for the combination therapy with radiation and drugs in diverse cancers.

  20. In vitro study on effect of germinated wheat on human breast cancer cells

    Science.gov (United States)

    This research investigated the possible anti-cancer effects of germinated wheat flours (GWF) on cell growth and apoptosis of human breast cancer cells. In a series of in vitro experiments, estrogen receptor-positive (MCF-7) and negative (MDA-MB-231) cells were cultured and treated with GWF that wer...

  1. Effects of ovarian cancer G protein coupled receptor 1 on the proliferation, migration, and adhesion of human ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    REN Juan; ZHANG Long

    2011-01-01

    Background OGR1 was found as a G-protein coupled receptor (GPCR) and proton sensor. Our previous studies have found that OGR1 has inhibitory effect on the metastasis of prostate cancer. In order to investigate the roles of OGR1 gene in the biological activities of ovarian cancer, we studied the OGR1 effects on ovarian cancer cells, HEY cells.Methods OGR1 gene was transfected into HEY cell, in which endogenous expression is low. OGR1-overxepressed cells and vector-transfected cells were compared in different assays. Western blotting was employed to confirm the high expression level of OGR1. Cell proliferation was determined by MTT assay and cell doubling time assay. Cell migration assay (transwell assay) and cell adhesion assay were performed to determine the migration and adhesion potential of cells. Student's t test was employed for statistical analysis.Results Proliferation of OGR1-overexpressed cells was significantly reduced (P <0.01); cell migration was significantly inhibited in the OGR1-transfected cells (P <0.01); cell adhesion to extracellular matrix including fibronectin, vitronectin,collagen Ⅰ/Ⅳ was significantly increased (P <0.01).Conclusions OGR1 expression in human ovarian cancer cells significantly inhibited the cell proliferation and migration,but significantly enhanced cell adhesion to the extracellular matrix. It indicated that OGR1 may be a tumor suppressor gene for ovarian cancer.

  2. Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells.

    Science.gov (United States)

    Yamamoto, Tetsushi; Uemura, Kentaro; Moriyama, Kaho; Mitamura, Kuniko; Taga, Atsushi

    2015-04-01

    Maple syrup is a natural sweetener consumed by individuals of all ages throughout the world. Maple syrup contains not only carbohydrates such as sucrose but also various components such as organic acids, amino acids, vitamins and phenolic compounds. Recent studies have shown that these phenolic compounds in maple syrup may possess various activities such as decreasing the blood glucose level and an anticancer effect. In this study, we examined the effect of three types of maple syrup, classified by color, on the cell proliferation, migration and invasion of colorectal cancer (CRC) cells in order to investigate whether the maple syrup is suitable as a phytomedicine for cancer treatment. CRC cells that were administered maple syrup showed significantly lower growth rates than cells that were administered sucrose. In addition, administration of maple syrup to CRC cells caused inhibition of cell invasion, while there was no effect on cell migration. Administration of maple syrup clearly inhibited AKT phosphorylation, while there was no effect on ERK phosphorylation. These data suggest that maple syrup might inhibit cell proliferation and invasion through suppression of AKT activation and be suitable as a phytomedicine for CRC treatment, with fewer adverse effects than traditional chemotherapy.

  3. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    Science.gov (United States)

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent

  4. Effects of allitridi on cell cycle arrest of human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Min-Wen Ha; Rui Ma; Li-Ping Shun; Yue-Hua Gong; Yuan Yuan

    2005-01-01

    AIM: To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism.METHODS: Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope.Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT-PCR was used to examine expression of the p21WAF1 gene.RESULTS: MGC803 cell growth was inhibited by allitridi with 24 h IC50 being 6.4 μg/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3 μg/mL.After being treated with allitridi at the concentration of 12 μg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula,and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 μg/mL for 24 h, the percentage of G0/G1 phase cells was decreased and that of G2/M phase cells was significantly increased (P = 0.002)compared with those in the group. When cells were treated with allitridi at the concentration of 6 μg/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21WAF1 gene of MGC803 cells and p21WAF1 gene of SGC7901 cells were remarkably upregulated after treatment.CONCLUSION: Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phas e may be associated with the upregulation of p21WAF1 genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.

  5. Effect of sirolimus on urinary bladder cancer T24 cell line

    Directory of Open Access Journals (Sweden)

    Oliveira Paula A

    2009-01-01

    Full Text Available Abstract Background Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. Methods T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viability of T24 cell line was determined by Trypan blue exclusion analysis. Results Sirolimus inhibits the growth of bladder carcinoma cells and decreases their viability. Significant correlations were found between cell proliferation and sirolimus concentration (r = 0.830; p Conclusion Sirolimus has an anti-proliferation effect on the T24 bladder carcinoma cell line. The information from our results is useful for a better understanding sirolimus's anti-proliferative activity in the T24 bladder cancer cell line.

  6. Modeling core metabolism in cancer cells: surveying the topology underlying the Warburg effect.

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    Osbaldo Resendis-Antonio

    Full Text Available BACKGROUND: Alterations on glucose consumption and biosynthetic activity of amino acids, lipids and nucleotides are metabolic changes for sustaining cell proliferation in cancer cells. Irrevocable evidence of this fact is the Warburg effect which establishes that cancer cells prefers glycolysis over oxidative phosphorylation to generate ATP. Regulatory action over metabolic enzymes has opened a new window for designing more effective anti-cancer treatments. This enterprise is not trivial and the development of computational models that contribute to identifying potential enzymes for breaking the robustness of cancer cells is a priority. METHODOLOGY/PRINCIPAL FINDINGS: This work presents a constraint-base modeling of the most experimentally studied metabolic pathways supporting cancer cells: glycolysis, TCA cycle, pentose phosphate, glutaminolysis and oxidative phosphorylation. To evaluate its predictive capacities, a growth kinetics study for Hela cell lines was accomplished and qualitatively compared with in silico predictions. Furthermore, based on pure computational criteria, we concluded that a set of enzymes (such as lactate dehydrogenase and pyruvate dehydrogenase perform a pivotal role in cancer cell growth, findings supported by an experimental counterpart. CONCLUSIONS/SIGNIFICANCE: Alterations on metabolic activity are crucial to initiate and sustain cancer phenotype. In this work, we analyzed the phenotype capacities emerged from a constructed metabolic network conformed by the most experimentally studied pathways sustaining cancer cell growth. Remarkably, in silico model was able to resemble the physiological conditions in cancer cells and successfully identified some enzymes currently studied by its therapeutic effect. Overall, we supplied evidence that constraint-based modeling constitutes a promising computational platform to: 1 integrate high throughput technology and establish a crosstalk between experimental validation and in

  7. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  8. Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines

    Indian Academy of Sciences (India)

    Simon Mahoney; Frank Arfuso; Pierra Rogers; Susan Hisheh; David Brown; Michael Millward; Arun Dharmarajan

    2012-03-01

    Phenoxodiol is an isoflavone derivative that has been shown to elicit cytotoxic effects against a broad range of human cancers. We examined the effect of phenoxodiol on cell death pathways on the prostate cell lines LNCaP, DU145 and PC3, representative of different stages of prostate cancer, and its effects on cell death pathways in these cell lines. Cell proliferation assays demonstrated a significant reduction in the rate of cell proliferation after 48 h exposure to phenoxodiol (10 and 30 M). FACS analysis and 3′-end labelling indicated that all three prostate cancer cell lines underwent substantial levels of cell death 48 h after treatment. Mitochondrial membrane depolarization, indicative of early-stage cell death signalling, using JC-1 detection, was also apparent in all cell lines after exposure to phenoxodiol in the absence of caspase-3 activation. Caspase inhibition assays indicated that phenoxodiol operates through a caspase-independent cell death pathway. These data demonstrate that phenoxodiol elicits anti-cancer effects in prostate cancer cell lines representative of early and later stages of development through an as-yet-unknown cell death mechanism. These data warrant the further investigation of phenoxodiol as a potential treatment for prostate cancer.

  9. Effect of p27KIP1 on cell cycle and apoptosis in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Wei-Zhong Wang; Kai-Zong Li; Wen-Xian Guan; Wei Yan

    2005-01-01

    AIM: To elucidate the effect of p27KIP1 on cell cycle and apoptosis regulation in gastric carcinoma cells.METHODS: The whole length of p27KIP1 cDNA was transfected into human gastric cancer cell line SCG7901by lipofectamine. Expression of p27KIP1 protein or mRNA was analyzed by Western blot and RNA dot blotting,respectively. Effect of p27KIP1 on cell growth was observed by MTT assay and anchorage-independent growth in soft agar. Tumorigenicity in nude mice was used to assess the in vivo biological effect of p27KIP1. Flow cytometry,TUNEL, and electron microscopy were used to assess the effect of p27KIP1 on cell cycle and apoptosis.RESULTS: Expression of p27KIP1 protein or mRNA increased evidently in SCG7901 cells transfected with p27KIP1. The cell growth was reduced by 31% at 48 h after induction with zinc determined by cell viability assay. The alteration of cell malignant phenotype was evidently indicated by the loss of anchorage-independent growth ability in soft agar. The tumorigenicity in nude mice was reduced evidently (0.55±0.14 cm vs 1.36±0.13crn, P<0.01). p27KIP1 overexpression caused cell arrest with 36% increase (from 33.7% to 69.3%,P<0.01) in G1 population. Prolonged p27KIP1 expression induced apoptotic cell death reflected by pre-G1 peak in the histogram of FACS, which was also confirmed by TUNEL assay and electron microscopy.CONCLUSION: p27KIP1 can prolong cell cycle in G1phase and lead to apoptosis. p27KIP1 may be a good candidate for cancer gene therapy.

  10. Effects of Fluid Shear Stress on Cancer Stem Cell Viability

    Science.gov (United States)

    Sunday, Brittney; Triantafillu, Ursula; Domier, Ria; Kim, Yonghyun

    2014-11-01

    Cancer stem cells (CSCs), which are believed to be the source of tumor formation, are exposed to fluid shear stress as a result of blood flow within the blood vessels. It was theorized that CSCs would be less susceptible to cell death than non-CSCs after both types of cell were exposed to a fluid shear stress, and that higher levels of fluid shear stress would result in lower levels of cell viability for both cell types. To test this hypothesis, U87 glioblastoma cells were cultured adherently (containing smaller populations of CSCs) and spherically (containing larger populations of CSCs). They were exposed to fluid shear stress in a simulated blood flow through a 125-micrometer diameter polyetheretherketone (PEEK) tubing using a syringe pump. After exposure, cell viability data was collected using a BioRad TC20 Automated Cell Counter. Each cell type was tested at three physiological shear stress values: 5, 20, and 60 dynes per centimeter squared. In general, it was found that the CSC-enriched U87 sphere cells had higher cell viability than the CSC-depleted U87 adherent cancer cells. Interestingly, it was also observed that the cell viability was not negatively affected by the higher fluid shear stress values in the tested range. In future follow-up studies, higher shear stresses will be tested. Furthermore, CSCs from different tumor origins (e.g. breast tumor, prostate tumor) will be tested to determine cell-specific shear sensitivity. National Science Foundation Grant #1358991 supported the first author as an REU student.

  11. Effects of Curcuma longa Extract on Telomerase Activity in Lung and Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nosratollah Zarghami

    2014-10-01

    Full Text Available Background: The purpose of this study is to evaluate the effect of Curcuma longa extract on the telomerase gene expression in QU-DB lung cancer and T47D breast cancer cell lines. Materials and Methods: The present study is an experimental research. Using 3 different phases n-hexane, dichloromethane and methanol, total extract of Curcuma longa in a serial dilution was prepared and three phases was analyzed for determining which phase has more curcuminoids. Then the extract cytotoxicity effect was tested on breast cancer cell line (T47D, and lung cancer cell line (QU-DB by 24, 48 and 72 h MTT (Dimethyl thiazolyl diphenyl tetrazolium assay. Then, the cells were treated with serial concentrations of the extract. Finally, total protein was extracted from the control and test groups, its quantity was determined and telomeric repeat amplification protocol (TRAP assay was performed for measurement of possible inhibition of the telomerase activity. Results: Cell viability and MTT-based cytotoxicity assay show that the total extract of Curcuma longa has cytotoxic effect with different IC50s in breast and lung cancer cell lines. Analysis of TRAP assay also shows a significant reduction in telomerase activity on both cancer cells with different levels. Conclusion: Curcuma longa extract has anti-proliferation and telomerase inhibitory effects on QU-DB lung cancer and T47D breast cancer cells with differences in levels of telomerase inhibition.

  12. The effect of adenovirus-mediated gene expression of FHIT in small cell lung cancer cells

    DEFF Research Database (Denmark)

    Zandi, Roza; Xu, Kai; Poulsen, Hans S

    2011-01-01

    The candidate tumor suppressor fragile histidine traid (FHIT) is frequently inactivated in small cell lung cancer (SCLC). Mutations in the p53 gene also occur in the majority of SCLC leading to the accumulation of the mutant protein. Here we evaluated the effect of FHIT gene therapy alone...... or in combination with the mutant p53-reactivating molecule, PRIMA-1(Met)/APR-246, in SCLC. Overexpression of FHIT by recombinant adenoviral vector (Ad-FHIT)-mediated gene transfer in SCLC cells inhibited their growth by inducing apoptosis and when combined with PRIMA-1(Met)/APR-246, a synergistic cell growth...

  13. Antitumor Effect of Antisense Ornithine Decarboxylase Adenovirus on Human Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Hui TIAN; Lin LI; Xian-Xi LIU; Yan ZHANG

    2006-01-01

    Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially lung cancer cells. Some chemotherapeutic agents aimed at decreasing ODC gene expression showed inhibitory effects on cancer cells. In this study, we examined the effects of adenoviral transduced antisense ODC on lung cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was used to infect lung cancer cell line A-549. The 3-(4,5-me thylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to analyze the effect on cell growth. Expression of ODC and concentration of polyamines in cells were determined by Western blot analysis and high performance liquid chromatography. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling was used to analyze cell apoptosis. The expression of ODC in A-549 cells was reduced to 54%, and that of three polyamines was also decreased through the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling showed that rAd-ODC/Ex3as could lead to cell apoptosis, with apoptosis index of 46%. This study suggests that rAd-ODC/Ex3as has an antitumor effect on the human lung cancer cells.

  14. Effect of chymotrypsin C and related proteins on pancreatic cancer cell migration

    Institute of Scientific and Technical Information of China (English)

    Haibo Wang; Wei Sha; Zhixue Liu; Cheng-Wu Chi

    2011-01-01

    Pancreatic cancer is a malignant cancer with a bigh mortality rate. The amount of chymotrypsin C in pancreatic cancer cells is only 20% of that found in normal cells.Chymotrypsin C has been reported to be involved in cancer cell apoptosis, but its effect on pancreatic cancer cell migration is unclear. We performed cell migration scratch assays and Transwell experiments, and found that cell migration ability was downregulated in pancreatic cancer Aspc-1 cells that overexpressed chymotrypsin C, whereas the cell migration ability was upregulated in Aspc-1 cells in which chymotrypsin C was suppressed. Two-dimensional fluorescence differential in gel electrophoresis/mass spectrometry method was used to identify the proteins that were differentially expressed in Aspc-1 cells that were transfected with plasmids to induce either overexpression or suppressed expression of chymotrypsin C. Among 26 identified differential proteins, cytokeratin 18 was most obviously correlated with chymotrypsin C expression. Cytokeratin 18 is expressed in developmental tissues in early stages of cancer,and is highly expressed in most carcinomas. We speculated that chymotrypsin C might regulate pancreatic cancer cell migration in relation to cytokeratin 18 expression.

  15. Effects of resistin-like molecule β over-expression on gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Li-Duan Zheng; Chun-Lei Yang; Teng Qi; Meng Qi; Ling Tong; Qiang-Song Tong

    2012-01-01

    AIM:To investigate the effects of resistin-like molecule β (RELMβ) over-expression on the invasion,metastasis and angiogenesis of gastric cancer cells.METHODS:Human RELMβ encoding expression vector was constructed and transfected into the RELMβ lowly-expressed gastric cancer cell lines SGC-7901 and MKN-45.Gene expression was measured by Western blotting,reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR.Cell proliferation was measured by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetry,colony formation and 5-ethynyl-20-deoxyuridine incorporation assays.The in vitro migration,invasion and metastasis of cancer cells were measured by cell adhesion assay,scratch assay and matrigel invasion assay.The angiogenic capabilities of cancer cells were measured by tube formation of endothelial cells.RESULTS:Transfection of RELMβ vector into SGC-7901 and MKN-45 cells resulted in over-expression of RELMβ,which did not influence the cellular proliferation.However,over-expression of RELMβ suppressed the in vitro adhesion,invasion and metastasis of cancer cells,accompanied by decreased expression of matrix metalloproteinase-2 (MMP-2) and MMP-9.Moreover,transfection of RELMβ attenuated the expression of vascular endothelial growth factor and in vitro angiogenic capabilities of cancer cells.CONCLUSION:Over-expression of RELMβ abolishes the invasion,metastasis and angiogenesis of gastric cancer cells in vitro,suggesting its potentials as a novel therapeutic target for gastric cancer.

  16. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Science.gov (United States)

    Atashpour, Shekoufeh; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Barzegar, Elmira; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-01-01

    Objective(s): The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133+ CSCs. Materials and Methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: The CD133+ CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. Conclusion: The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells. PMID:26351552

  17. Myxoma Virus Sensitizes Cancer Cells to Gemcitabine and Is an Effective Oncolytic Virotherapeutic in Models of Disseminated Pancreatic Cancer

    OpenAIRE

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M.; Mona, Mahmoud; McFadden, Grant

    2012-01-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and comb...

  18. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

    2013-10-01

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  19. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-10-15

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  20. Paclitaxel augments cytotoxic effect of photodynamic therapy using verteporfin in gastric and bile duct cancer cells.

    Science.gov (United States)

    Park, Seungwoo; Hong, Sung Pil; Oh, Tae Yoon; Bang, Seungmin; Chung, Jae Bock; Song, Si Young

    2008-07-01

    Photodynamic therapy (PDT) shows a limited antitumor effect in treating gastrointestinal tumors because of improper light penetration or insufficient photosensitizer uptake. The aim of this study was to evaluate the cytotoxic effect of PDT combined with paclitaxel on in vitro cancer cells. In vitro photodynamic therapy was performed in gastric cancer cells (NCI-N87) and bile duct cancer cells (YGIC-6B) using verteporfin (2 ug mL(-1)) and a PTH light source (1 000 W, Oriel Co.) with 665-675 nm narrow band pass filter. Cytotoxicity was compared using the MTT assay between cancer cells treated with PDT alone or pretreated with paclitaxel (IC(25)). Apoptotic changes were evaluated using DAPI staining, DNA fragmentation analysis, Annexin V-FITC apoptosis assay, cell cycle analysis, and western blots for cytochrome c, Bax, and Bid. The PDT-induced cytotoxicity was potentiated by pretreating with low dose paclitaxel (P cancer therapy.

  1. The Inhibitory Effect of Oridonin on the Growth of Fifteen Human Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Junhui Chen; Shaobin Wang; Dongyang Chen; Guisheng Chang; Qingfeng Xin; Shoujun Yuan; Zhongying Shen

    2007-01-01

    OBJECTIVE To study the inhibitory effect of oridonin on the growth of cancer cells.METHODS Fifteen human cancer cell lines were subjected to various concentrations of oridonin in culture medium.The inhibitory rate of cell growth was measured by the MTT assay.and compared with a negative control and 5-Fu-positive control.RESULTS The 50% inhibiting concentration (IC50) and maximal inhibi tion (Imax) of oridonin shown by studying the growth of the cancer cell lines were as follows:leukemias (HL60 cells:3.9 μg/ml and 73.8%.K562 cells:4.3 μg/ml and 76.2%):esophageal cancers (SHEEC cells:15.4 μg/ml and 99.2%,Eca109 cells:15.1 μg/ml and 84.6%,TE1 cells:4.0 μg/ml and 70.2%):gastric cancers (BGC823 cells:7.6 μg/ml and 98.7%,SGC7901 cells:12.3 μg/ml and 85.7%):colon cancers (HT29 cells:13.6 μg/ml and 97.2%,HCT cells:14.5 μg/ml and 96.5%):liver cancers (Bel7402 cells:15.2 μg/ml and 89.2%,HepG2 cells:7.1 μg/ml and 88.3%):pancreatic cancer (PC3 cells:11.3 μg/ml and 68.4%):lung cancer (A549 cells:18.6 μg/ml and 98.0%):breast cancer (MCF7 cells:18.4 μg/ml and 84.7%):uterine cervix cancer (Hela cells:13.7μg/ml and 98.5%).CONCLUSION Oridonin had a relatively wide anti-tumor spectrum,and a relatively strong inhibitory effect on the growth of the 15 human cancer cells.Inhibitory effects were concentration dependent.

  2. Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HAO Ji-qing; LI Qi; XU Shu-ping; SHEN Yu-xian; SUN Gen-yun

    2008-01-01

    Background Lumiracoxib is a highly selective cyclooxygenase-2(COX-2)inhibitor with antiinflammatory,analgesic and antipyretic activities comparable with class specific drugs,but with much improved gastrointestinal safety.No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Drug-drug interactions were analyzed using the coefficient of drug interaction(CDI)to characterize the interactions as synergism,additivity or antagonism.Morphological changes were observed by acridine orange fluorescent staining.Extent of apoptosis was determined by flow cytometry.Results Lumiracoxib(15-240 μmol/L)has an inhibitory effect on the proliferation of A549 and NCI-H460 celllines in concentration- and time-dependent manners with the IC50 values of 2597 μmol/L and 833 pmol/L,respectively.The synergistic effect was prominent when lumiracoxib(15-240 μmol/L)was combined with docetaxol(0.2-2 μmol/L)(CDI <1).Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells.Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol,which may be related to apoptotic induction and cell cycle arrest.

  3. Radiosensitization effects of sorafenib on colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Mi-Sook; Jung, Won-Gyun; Jeong, Youn Kyoung [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-11-15

    Radiotherapy is a standard therapy in the adjuvant treatment of resected colon and rectum cancers, and its combination with chemotherapy has been shown to reduce local failure and distant metastasis still further, thereby improving the outcome of treatment. One potential chemotherapeutic agent for this, sorafenib (Nexavar, BAY43-9006), is an oral multikinase inhibitor that blocks tumor cell proliferation and angiogenesis, and induces tumor cell apoptosis by inhibiting serine/threonine kinases (c-RAF and mutant and wild-type BRAF) as well as the receptor tyrosine kinases vascular endothelial growth factor receptor 2 and 3 (VEGFR2 and VEGFR3), platelet- derived growth factor receptor , FLT3, and c-KIT. Sorafenib is currently used in clinics to treat patients with advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. These findings provide a molecular evidence base for the use of chemoradiation to treat colon cancer, and in vivo modeling should be used to further assess its suitability for clinical applications.

  4. Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs

    OpenAIRE

    HERTZ, EVERALDO; CADONÁ, FRANCINE CARLA; Machado, Alencar Kolinski; Azzolin, Verônica; HOLMRICH, SABRINA; ASSMANN, CHARLES; LEDUR, PAULINE; RIBEIRO, EULER ESTEVES; DE SOUZA FILHO, OLMIRO CEZIMBRA; MÂNICA-CATTANI, MARIA FERNANDA; DA CRUZ, IVANA BEATRICE MÂNICA

    2014-01-01

    Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the trea...

  5. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

    Science.gov (United States)

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells.

  6. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com; Cao, Zhifei, E-mail: hunancao@163.com

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.

  7. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational.

  8. Effect of soy saponin on the growth of human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Cheng-Yu; Tsai; Yue-Hwa; Chen; Yi-Wen; Chien; Wen-Hsuan; Huang; Shyh-Hsiang; Lin

    2010-01-01

    AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the effect on cell growth,cell morphology,alkaline phosphatase(AP) and protein kinase C(PKC) activities,and P53 protein,c-Fos and c-Jun gene expression.RESULTS:Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-Otetradecanol-phorbol-13-acetate-stimulated PKC ...

  9. The effect pathway of retinoic acid through regulation of retinoic acid receptor in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Qiao Wu; Zheng-Ming Chen; Wen-Jin Su

    2001-01-01

    AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.``

  10. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the sphingosine 1phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells. METHODS: S1P receptor expression profile in human esophageal squamous cell carcinoma cell line Eca109 was detected by semiquantitative reverse trans cription polymerase chain reaction. Eca109 cells were stably transfected with S1P5EGFP or controlEGFP constructs. The relation between the responses of cell prol...

  11. Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion.

    Science.gov (United States)

    Shin, Dong Hoon; Choi, Yong-Joon; Jin, Peng; Yoon, Haejin; Chun, Yang-Sook; Shin, Hyun-Woo; Kim, Ja-Eun; Park, Jong-Wan

    2016-04-26

    The lysyl deacetylase SIRT1 acts as a metabolic sensor in adjusting metabolic imbalance. To explore the role of SIRT1 in tumor-stroma interplay, we designed an in vivo tumor model using SIRT1-transgenic mice. B16F10 mouse melanoma grew more quickly in SIRT1-transgenic mice than in wild-type mice, whereas SIRT1-overexpressing one grew slowly in both mice. Of human tumors, SIRT1 expression in stromal fibroblasts was found to correlate with poor prognosis in ovarian cancer. B16F10 and human ovarian cancer (SKOV3 and SNU840) cells were more proliferative in co-culture with SIRT1-overexpressiong fibroblasts. In contrast, SIRT1 within cancer cells has a negative effect on cell proliferation. In conditioned media from SIRT1-overexpressing fibroblasts, matrix metalloproteinase-3 (MMP3) was identified in cytokine arrays to be secreted from fibroblasts SIRT1-dependently. Fibroblast-derived MMP3 stimulated cancer cell proliferation, and such a role of MMP3 was also demonstrated in cancer/fibroblast co-grafts. In conclusion, SIRT1 plays differential roles in cancer and stromal cells. SIRT1 in stromal cells promotes cancer growth by producing MMP3, whereas SIRT1 in cancer cells inhibits growth via an intracellular event. The present study provides a basis for setting new anticancer strategies targeting SIRT1.

  12. Effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Zheng Wu; Yi Lüi; Bo Wang; Chang Liu; Zuo-Ren Wang,

    2003-01-01

    AIM: Pancreatic cancer in the head is frequently accompanied by jaundice and high bile acid level in serum. This study focused on the direct effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer.METHODS: Pancreatic cancer cell lines PANC-1, MIA PaCa2 and PGHAM-1 were explored in this study. The cell lines were cultured in media supplemented with certain bile acids,CA, DCA, LCA, TCDC, TDCA and GCA. Their influence on cell growth was measured with MTT assay after 72 h of incubation. Cell cycles of PANC-1 cells in 40 μM of bile acids media were analyzed by flow cytometry. Ultrastructural alteration of PANC-1 cells induced by DCA was observed using scanning and transmission electron microscope (SEM and TEM).RESULTS: At various concentrations of bile acids and incubation time, no enhanced effects of bile acids on cell proliferation were observed. Significant inhibitory effects were obtained in almost all media with bile acids. DCA and CA increased the percentage of G0+G1 phase cells, while GCA and TDCA elevated the S phase cell number. After 48 h of incubation in DCA medium, PANC-1 cells showed some structural damages such as loss of their microvilli and vacuolization of organelles in cytoplasm.CONCLUSION: Bile acids can reduce proliferation of pancreatic cancer cells due to their direct cytotoxicity. This result implies that elevation of bile acids in jaundiced serum may inhibit pancreatic cancer progression.

  13. Ethanolic Extract Cytotoxic Effect of Zingiber Afficinale in Breast Cancer (MCF7 Cell Line

    Directory of Open Access Journals (Sweden)

    J Tavakkol Afshari

    2010-07-01

    Full Text Available Introduction & Objective: Biological activities of Zingiber afficieale plants have been reported as possessing anticancer, antibacterial, anti ulcer, antifungal, and insecticidal properties. However, its antitumor effects haven't been studied in cancer cell lines. The aim of this study was to investigate the antitumor effect of zingiber afficieale on breast cancer cell lines. Materials & Methods: This experimental study was conducted in 2010 at Mashhad University of medical Sciences. Breast cancer cell line (MCF7 and normal connective tissue cell line (L929 were cultured in DMEM medium. Ethanolic extract of Zingiber afficinale was prepared and cell lines were treated with different concentration of extract (5000 to 78 µg. Cell viability was measured by MTT assay after 24, 48, and 72 hours. The collected data were statistically analyzed by SPSS software. Results: The effects of Zingiber afficinale on cell viability were observed after 48 hours on cell lines. Ginger doses in 2500 µg concentration inhibited 50% of cell growth (IC50 in cell lines after 48 hours. Conclusion: Our study revealed that fresh ginger extract has cytotoxic effects on tumor cells, but it doesn’t have any cytotoxic effect on normal cells. It seems that ginger could be considered as a promising chemotherapeutic agent in cancer treatment.

  14. Effects of Chemotherapy-Induced Alterations in Cell Mechanical Properties on Cancer Metastasis

    Science.gov (United States)

    Prathivadhi, Sruti; Ekpenyong, Andrew; Nichols, Michael; Taylor, Carolyn; Ning, Jianhao

    Biological cells can modulate their mechanical properties to suit their functions and in response to changes in their environment. Thus, mechanical phenotyping of cells has been employed for tracking stem cell differentiation, bacterial infection, cell death, etc. Malignant transformation of cells also involves changes in mechanical properties. However, the extent to which mechanical properties of cancer cells contribute to metastasis is not well understood. Yet, more than 90% of all cancer deaths are directly related to metastasis. Transit of cells through the microcirculation is one of the key features of metastasis. We hypothesize that cancer treatment regimens do inadvertently alter cell mechanical properties in ways that might promote cancer metastasis. We use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that cancer cells treated with chemotherapeutic drugs such as daunorubicin, become more deformable at short timescales (0.1 s) and transit faster through the device. Our results are first steps in evaluating the pro- or anti-metastatic effects of chemotherapeutic drugs based on their induced alterations in cell mechanical properties.

  15. Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Isaac Antolín

    2013-03-01

    Full Text Available It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect.

  16. Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells.

    Science.gov (United States)

    Sakamoto, Takako; Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio

    2010-09-01

    Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappaB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17beta-estradiol (E(2)). E(2) increased cell growth significantly, coumestrol increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G(1)/S transition in cell cycle analysis, similar to E(2). This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein. Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-kappaB-dependent transcriptional activity. On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) alpha silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERalpha silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity.

  17. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  18. Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis

    OpenAIRE

    Lee, Hwan Hee; Lee, Seulki; Lee, Kanghyo; Shin, Yu Su; Kang, Hyojeung; Cho, Hyosun

    2015-01-01

    Background Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO. Methods RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h an...

  19. Cloning of WWOX Gene and Its Growth-inhibiting Effects on Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    熊宙芳; 胡沙; 王泽华

    2010-01-01

    The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reactio...

  20. TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells.

    Science.gov (United States)

    Moniri, M R; Sun, X-Y; Rayat, J; Dai, D; Ao, Z; He, Z; Verchere, C B; Dai, L-J; Warnock, G L

    2012-09-01

    Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC(nsTRAIL) and MSC(stTRAIL). The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.

  1. Effect of Cytokine on the Expression of Sodium Iodide Symporter Gene in Breast Cancer Cell

    Institute of Scientific and Technical Information of China (English)

    JIAYue; LIUChao; TANGWei; LIUCui-ping; QINYou-wen; YUANQing-xing; LIQian; MAOXiao-dong; DIFu-song

    2004-01-01

    To investigate the effect of cytokines (TNF-α, IFN-γ and IL-6) on the expression of sodi-um-iodide symporter(NIS) gene in breast cancer cell (MCF-7). Methods:The breast cancer cell was cultureds with negative control culture or cultures with different concentrations of cytokines for 72 h. NIS germ mRNA in breast cancer cells cultured was determined by reverse transcriptase-polymerase chain reaction(RT-PCR). Results:Expression of sodium-iodide symporter mRNA can be found decreasing along with increasing the concentration of cytokine dose-depen-dently. Conchzs/on ~ Cytokine may play a role in iodide-uptake modulating in breast cancer cells by their effect on NIS germ expression.

  2. The Suppression Effect of Light Rare Earth Elements on Proliferation of Two Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    JIYUN-JING; XIAOBAI; 等

    2000-01-01

    To study the suppression effect of light rare earth elements(RE) on proliferation of two cancer cell lines.Two cancer cell lines PAMC82 and K562 were used to examine their colony-forming ability in soft agar,microtubule structure,calmodulin levels and regulation of smoe gene expressions y Northern blot analysis with and without treatment by RE.The results showed that on soft agar culture the colony-forming ability of human gastric cancer cell line PAMC82 treated by RE chloride decreased and the PAMC82 cell microtubule abnormal structure became normal.The calmodulin (CaM) levels decreased in human leukemia cells(k562) treated with cerium chloride and neodymium chloride.The Northern blot analysis revealed marked up-regulation of p53,p16(MTS1),p21(WAF1) gene expressions in PAMC82 cells treated with lanthanum chloride and cerium chloride,as compared to control PAMC82 cells,The light rare earth elements studied have certain suppression effects on proliferation of cancer cells,This effect might be realted to the decrease of calmodulin and up-regulationg of smoe gene expressions in cancer cells.

  3. The Suppression Effect of Light Rare Earth Elements on Proliferation of Two Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the suppression effect of light rare earth elements (RE) on proliferation of two cancer cell lines. Two cancer cell lines PAMC82 and K562 were used to examine their colony-forming ability in soft agar, microtubule structure, calmodulin levels and regulation of some gene expressions by Northern blot analysis with and without treatment by RE. The results showed that on soft agar culture the colony-forming ability of human gastric cancer cell line PAMC82 treated by RE chloride decreased and the PAMC82 cell microtubule abnormal structure became normal. The calmodulin (CaM) levels decreased in human leukemia cells (K562) treated with cerium chloride and neodymium chloride. The Northern blot analysis revealed marked up-regulation of p53, p16(MTS1), p21(WAF1) gene expressions in PAMC82 cells treated with lanthanum chloride and cerium chloride, as compared to control PAMC82 cells. The light rare earth elements studied have certain suppression effects on proliferation of cancer cells. This effect might be related to the decrease of calmodulin and up-regulation of some gene expressions in cancer cells.

  4. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yoke Keong Yong

    2013-01-01

    Full Text Available Clinacanthus nutans Lindau leaves (CN have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T, K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals, but less effective in negating nitric oxide and hydrogen peroxide radicals. Chloroform extract exerted the highest antiproliferative effect on K-562 (91.28±0.03% and Raji cell lines (88.97±1.07% at 100 μg/ml and the other five cancer cell lines in a concentration-dependent manner, but not on IMR-32 cells. Fourteen known compounds were identified in chloroform extract, which was analysed by gas chromatography—mass spectra analysis. In conclusion, CN extracts possess antioxidant and antiproliferative properties against cultured cancer cell lines, suggesting an alternate adjunctive regimen for cancer prevention or treatment.

  5. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines.

    Science.gov (United States)

    Yong, Yoke Keong; Tan, Jun Jie; Teh, Soek Sin; Mah, Siau Hui; Ee, Gwendoline Cheng Lian; Chiong, Hoe Siong; Ahmad, Zuraini

    2013-01-01

    Clinacanthus nutans Lindau leaves (CN) have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T, K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals, but less effective in negating nitric oxide and hydrogen peroxide radicals. Chloroform extract exerted the highest antiproliferative effect on K-562 (91.28 ± 0.03%) and Raji cell lines (88.97 ± 1.07%) at 100  μ g/ml and the other five cancer cell lines in a concentration-dependent manner, but not on IMR-32 cells. Fourteen known compounds were identified in chloroform extract, which was analysed by gas chromatography-mass spectra analysis. In conclusion, CN extracts possess antioxidant and antiproliferative properties against cultured cancer cell lines, suggesting an alternate adjunctive regimen for cancer prevention or treatment.

  6. Multiple Effects of Berberine Derivatives on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Luis Miguel Guamán Ortiz

    2014-01-01

    Full Text Available The pharmacological use of the plant alkaloid berberine is based on its antibacterial and anti-inflammatory properties; recently, anticancer activity has been attributed to this compound. To exploit this interesting feature, we synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and we tested their effects on two human colon carcinoma cell lines, that is, HCT116 and SW613-B3, which are characterized by wt and mutated p53, respectively. We observed that cell proliferation is more affected by cell treatment with the derivatives than with the lead compound; moreover, the derivatives proved to induce cell cycle arrest and cell death through apoptosis, thus suggesting that they could be promising anticancer drugs. Finally, we detected typical signs of autophagy in cells treated with berberine derivatives.

  7. Antitumour Effects of Isocurcumenol Isolated from Curcuma zedoaria Rhizomes on Human and Murine Cancer Cells

    OpenAIRE

    S. Lakshmi; G. Padmaja; Remani, P.

    2011-01-01

    Curcuma zedoaria belonging to the family Zingiberaceae has been used in the traditional system of medicine in India and Southwest Asia in treating many human ailments and is found to possess many biological activities. The rationale of the present study was to isolate, identify, and characterize antitumour principles from the rhizomes of Curcuma zedoaria, to assess its cytotoxic effects on human and murine cancer cells, to determine its apoptosis inducing capacity in cancer cells, and to eval...

  8. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川

    2003-01-01

    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  9. Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer.

    Science.gov (United States)

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M; Mona, Mahmoud; McFadden, Grant

    2012-04-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and combination therapy with gemcitabine was also evaluated. In cell culture, MYXV replication was robust in a broad range of pancreatic cancer cells and also showed increased oncolysis in combination with gemcitabine. In animal models, MYXV treatment conferred survival benefits over control or gemcitabine-treated cohorts regardless of the cell line or animal model used. MYXV monotherapy was most effective in an immunocompetent IPD model, and resulted in 60% long-term survivors. In Pan02 engrafted immunocompetent IPD models, sequential treatment in which MYXV was administered first, followed by gemcitabine, was the most effective and resulted in 100% long-term survivors. MYXV is an effective oncolytic virus for pancreatic cancer and can be combined with gemcitabine to enhance survival, particularly in the presence of an intact host immune system.

  10. Essential Oil from Myrica rubra Leaves Potentiated Antiproliferative and Prooxidative Effect of Doxorubicin and its Accumulation in Intestinal Cancer Cells.

    Science.gov (United States)

    Ambrož, Martin; Hanušová, Veronika; Skarka, Adam; Boušová, Iva; Králová, Věra; Langhasová, Lenka; Skálová, Lenka

    2016-01-01

    Essential oil from the leaves of Myrica rubra, a subtropical Asian fruit tree traditionally used in folk medicines, has a significant antiproliferative effect in several intestinal cancer cell lines. Doxorubicin belongs to the most important cytostatics used in cancer therapy. The present study was designed to evaluate the effects of defined essential oil from M. rubra leaves on efficacy, prooxidative effect, and accumulation of doxorubicin in cancer cell lines and in non-cancerous cells. For this purpose, intestinal adenocarcinoma CaCo2 cells were used. Human fibroblasts (periodontal ligament) and a primary culture of rat hepatocytes served as models of non-cancerous cells. The results showed that the sole essential oil from M. rubra has a strong prooxidative effect in cancer cells while it acts as a mild antioxidant in hepatocytes. Combined with doxorubicin, the essential oil enhanced the antiproliferative and prooxidative effects of doxorubicin in cancer cells. At higher concentrations, synergism of doxorubicin and essential oil from M. rubra was proved. In non-cancerous cells, the essential oil did not affect the toxicity of doxorubicin and the doxorubicin-mediated reactive oxygen species formation. The essential oil increased the intracellular concentration of doxorubicin and enhanced selectively the doxorubicin accumulation in nuclei of cancer cells. Taken together, essential oil from M. rubra leaves could be able to improve the doxorubicin efficacy in cancer cells due to an increased reactive oxygen species production, and the doxorubicin accumulation in nuclei of cancer cells.

  11. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

    OpenAIRE

    2013-01-01

    Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited th...

  12. Effects of bortezomib in sensitizing human prostate cancer cell lines to NK-mediated cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Wei Hu; Rui-Rui Zheng; Hui-Xia Cui; Dan Yue; Yong Wang; You-Hong Jiang

    2012-01-01

    The proteasome inhibitor,bortezomib,has been demonstrated to sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis.Natural killer (NK) cells represent potent antitumor effector cells.They also express TRAIL.Therefore.we investigated whether bortezomib could sensitize tumor cells to NK cell-mediated killing,and have the same effect in human prostate cancer cell lines (LNCaP and DU145).We found that bortezomib strongly inhibits proliferation in both cell lines.Furthermore,compared with LNCaP cells,DU 145 cells are more sensitive to bortezomib-induced apoptosis.However,bortezomib is unable to sensitize these two cell lines to NK cell-mediated killing in short-term assays.In long-term assays,we found that killing mediated by activated NK cells following bortezornib treatment leads to greater antitumor effects than either treatment alone.In addition,treatment with bortezomib causes these cells to upregulate apoptosis-related mRNA as well as death receptors and downregulate the major histocompatibility class (MHC)-Ⅰ molecule on the cell surface of DU145 cells.In contrast,LNCaP cells are not sensitized by this treatment.Death receptors and the MHC-Ⅰ molecule did not change in this cell line.These-data suggest that bortezomib can be used to sensitize prostate cancer cells to NK cell-mediated killing and improve current cancer therapies.This therapeutic strategy may be more effective in patients with androgen-insensitive prostate cancer.

  13. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chi-Chang Chang

    2014-12-01

    Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  14. Anti-proliferative effects of Siegesbeckia orientalis ethanol extract on human endometrial RL-95 cancer cells.

    Science.gov (United States)

    Chang, Chi-Chang; Hsu, Hsia-Fen; Huang, Kuo-Hung; Wu, Jing-Mei; Kuo, Shyh-Ming; Ling, Xue-Hua; Houng, Jer-Yiing

    2014-12-01

    Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  15. Photothermal effects of multi-walled carbon nanotubes on the viability of BT-474 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Hung-Tao [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Wang, Tsung-Pao [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Lee, Chi-Young [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Tai, Nyan-Hwa, E-mail: nhtai@mx.nthu.edu.tw [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Chang, Hwan-You, E-mail: hychang@mx.nthu.edu.tw [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China)

    2013-03-01

    Functionalized multi-walled carbon nanotubes (f-MWCNTs) were conjugated to an antibody of BT-474 cancer cells (f-MWCNTs-ab), and the photothermal effect of the f-MWCNTs-ab for BT-474 cancer cell destruction was demonstrated. After near-infrared irradiation, the f-MWCNTs-ab were more capable of killing cancer cells and possessed higher cell specificity than f-MWCNTs. Quantitative results showed that the viability of the cancer cells was affected by the concentration of the f-MWCNTs-ab solution, irradiation time, and settling time after irradiation. The membrane impermeable fluorescence dye ethidium bromide was used to detect cell viability after near-infrared irradiation, and the results agreed with those obtained from the Alamar Blue cell viability assay. The EtBr fluorescence results suggest that the cell membrane, attached to f-MWCNTs-ab, was damaged after irradiation, which led to cell death and necrosis. Using confocal microscopy, a few f-MWCNTs-ab were detected in the cell, indicating the endocytosis effect. The results not only explain the improved efficiency of thermotherapy but also indicate that necrosis may result from protein denaturation attributing to the heated f-MWCNTs-ab in the cell. Highlights: Black-Right-Pointing-Pointer f-MWCNTs conjugated with anti-HER2 antibody by chemical method. Black-Right-Pointing-Pointer Kill breast cancer cells by using low dose f-MWCNTs-ab due to photothermal effect. Black-Right-Pointing-Pointer Use EtBr fluorescent to prove that the cell membrane was broken by heated f-MWCNTs. Black-Right-Pointing-Pointer Few f-MWCNTs-ab were detected in the cell indicating the endocytosis effect. Black-Right-Pointing-Pointer Necrosis may result from protein denaturation due to contact with the heated CNTs.

  16. Effect of NK4 Transduction in Bone Marrow-Derived Mesenchymal Stem Cells on Biological Characteristics of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yun-Peng Sun

    2014-03-01

    Full Text Available Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.

  17. Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells.

    Science.gov (United States)

    Jakubowska-Mućka, Anna; Sieńko, Jacek; Zapała, Łukasz; Wolny, Rafał; Lasek, Witold

    2012-04-01

    Sulindac, a non-steroidal anti-inflammatory drug, suppresses carcinogenesis and inhibits growth of tumor cells. Pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, has been also identified as a potential anti-neoplastic agent. We hypothesized that combination of sulindac and PDTC could result in augmentation of cytotoxicity against ovarian cancer cells. The effect of sulindac and PDTC was examined on several ovarian cancer lines. Tumor cell viability was assessed using the MTT assay. Annexin-V/PI staining was used to detect apoptosis, cell cycle distribution was analyzed in FACS, and expression of cellular proteins was detected by western blotting. Incubation of OVA-14, OVP-10 and CAOV-1 ovarian cancer cells with sulindac and PDTC resulted in significantly greater inhibition of cell viability compared to either compound alone. In a model of OVA-14 cells it was evident that this effect was not related to the expression of COX enzymes since both active (sulindac sulfide) and inactive (sulindac) in vitro compounds affected the growth of tumor cells to a similar extent and synergized in cytotoxicity with PDTC. Combination of sulindac and PDTC lead to G0 arrest and massive apoptosis in co-treated cultures. Western blotting analysis argued for induction of the mitochondrial apoptotic pathway. These data demonstrate the synergistic cytotoxic effect of sulindac and PDTC on ovarian cancer cells through apoptosis and cell cycle arrest and prompt to test the efficacy of this combination in animal models.

  18. Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice.

    Science.gov (United States)

    Parajuli, P; Yano, S; Hanibuchi, M; Nokihara, H; Shinohara, T; Sone, S

    1998-02-01

    Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 micrograms/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction.

  19. Addiction to Coupling of the Warburg Effect with Glutamine Catabolism in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Bradley Smith

    2016-10-01

    Full Text Available Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2. Notably, GPT2 engages activated glycolysis to drive the utilization of glutamine as a carbon source for TCA cycle anaplerosis in colon cancer cells. Our data indicate that the Warburg effect supports oncogenesis via GPT2-mediated coupling of pyruvate production to glutamine catabolism. Although critical to the cancer phenotype, GPT2 activity is dispensable in cells that are not fully transformed, thus pinpointing a metabolic vulnerability specifically associated with cancer cell progression to malignancy.

  20. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Science.gov (United States)

    Guillen-Ahlers, Hector; Tan, Jiangning; Castellino, Francis J; Ploplis, Victoria A

    2011-01-01

    Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+) colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  1. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Directory of Open Access Journals (Sweden)

    Hector Guillen-Ahlers

    Full Text Available Matrix metalloproteinase 7 (MMP7, a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  2. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.

    Science.gov (United States)

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-07-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects.

  3. Effects of Thymus serpyllum extract on cell proliferation, apoptosis and epigenetic events in human breast cancer cells.

    Science.gov (United States)

    Bozkurt, Emir; Atmaca, Harika; Kisim, Asli; Uzunoglu, Selim; Uslu, Ruchan; Karaca, Burcak

    2012-01-01

    Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.

  4. Effect of leptin on cell proliferation and apoptosis of gastric adenocarcinoma cell line-SGC7901 and colon cancer cell line-HT-29

    Institute of Scientific and Technical Information of China (English)

    Chang-Wen Yu; Bi-Sheng Zhu

    2016-01-01

    Objective:To explore effect of leptin on cell proliferation and apoptosis of gastric adenocarcinoma cell line-SGC7901 and colon cancer cell line-HT-29.Methods: MTT and flow cytometry were adopted for detecting the effect of exogenous leptin on cell cycle of gastric adenocarcinoma cell line-SGC7901 and colon cancer cell line-HT-29.Results: Leptin with mass concentration (0 ng/mL, 5 ng/mL, 50 ng/mL, 100 ng/mL, 200 ng/mL) could stimulate the growth of gastric adenocarcinoma cell line-SGC7901 and colon cancer cell line-HT-29; exogenous leptin with mass concentration (5 ng/mL, 50 ng/mL, 100 ng/mL, 200 ng/mL) could inhibit cell growth of gastric adenocarcinoma cell line-SGC7901 and colon cancer cell line-HT-29 after 72 h; among which, inhibiting effects of cell line-SGC7901 and cell line-HT-29 were the most significant under the effect of exogenous leptin with mass concentration-200 ng/mL.Conclusion:Within a certain concentration and action time, exogenous leptin can stimulate the growth of gastric adenocarcinoma cell line and colon cancer cell line, and then promot the tumor cell proliferation and/or inhibit the tumor cell apoptosis.

  5. Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer.

    Science.gov (United States)

    Zhang, J-L; Yao, Q; Chen Y Wang, J-H; Wang, H; Fan, Q; Ling, R; Yi, J; Wang, L

    2015-03-20

    The objective of this study was to determine the changes in peripheral blood circulating tumor cells in HER2-positive early breast cancer before and after Herceptin therapy, and to explore the effects of the HER2 gene and Herceptin on circulating tumor cells. CK19 mRNA expression in peripheral blood was evaluated by qRT-PCR as an index of circulating tumor cells in 15 cases of HER-2-positive breast cancer and 18 cases of HER2-negative breast cancer before, and after chemotherapy as well. Ten cases of HER2-positive breast cancer continued on Herceptin therapy for 3 months after chemotherapy, and their peripheral blood was again drawn and assayed for CK-19 mRNA expression. Preoperatively, all cases of HER2-positive cancer were positive for CK19 mRNA in peripheral blood, but 6 cases of HER2-negative breast cancer were positive (33.3%), where there was a substantial difference between the two groups. After 6 cycles of adjuvant chemotherapy, CK19 positive rates in cases of HER2-positive and -negative breast cancer reduced by 93.3 and 11.1%, respectively, with a significant difference still existing. After 3 months of Herceptin therapy, expression of CK19 mRNA declined considerably in 10 cases of HER2 positive breast cancer (113.66 ± 88.65 vs 63.35 ± 49.27, P = 0.025). HER-2 gene expression closely correlated with circulating tumor cells in peripheral blood of early breast cancer patients. Moreover, Herceptin, a monoclonal antibody for HER2, can reduce the number of circulating tumor cells, which can be an early predictive factor for Herceptin therapy effectiveness against breast cancer.

  6. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Rabih El-Merahbi

    Full Text Available Cancer stem cells (CSCs, including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1 in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS. Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  7. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro.

    Science.gov (United States)

    Frajese, Giovanni Vanni; Benvenuto, Monica; Fantini, Massimo; Ambrosin, Elena; Sacchetti, Pamela; Masuelli, Laura; Giganti, Maria Gabriella; Modesti, Andrea; Bei, Roberto

    2016-06-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

  8. Evaluation of the effects of a plasma activated medium on cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mohades, S.; Laroussi, M., E-mail: mlarouss@odu.edu; Sears, J.; Barekzi, N.; Razavi, H. [Plasma Engineering and Medicine Institute, Old Dominion University, Norfolk, Virginia 23529 (United States)

    2015-12-15

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  9. Preliminary Study on Cytotoxic Effect of Biodegradation of Magnesium on Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Ling Ren; Mei Li; Xiao Lin; Huafu Zhao; Ke Yang

    2012-01-01

    Biodegradation of magnesium (Mg) based metals in body fluid can lead to a strong alkalinity as well as an increase of Mg2+ concentration in its surrounding environment. In vitro cytotoxic effects of the extracts of pure Mg with and without micro arc oxidation (MAO) coating on osteosarcoma U2-OS cells, a kind of bone cancer cells, were preliminarily studied, independently considering the increase of either alkalinity or Mg2+ concentration. The results indicated that the high alkalinity, i.e., a great increase of pH value, caused by the degradations of Mg with and without MAO coating in the culture medium all showed strong cytotoxic effects on U2-OS cells. However, the increase of Mg2+ concentration had no such cytotoxic effect. This finding may provide an alternative way to cure bone cancers through creating a high alkalinity surrounding the cancer cells.

  10. Evaluation of the effects of a plasma activated medium on cancer cells

    Science.gov (United States)

    Mohades, S.; Laroussi, M.; Sears, J.; Barekzi, N.; Razavi, H.

    2015-12-01

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  11. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines

    OpenAIRE

    Yoke Keong Yong; Jun Jie Tan; Soek Sin Teh; Siau Hui Mah; Gwendoline Cheng Lian Ee; Hoe Siong Chiong; Zuraini Ahmad

    2013-01-01

    Clinacanthus nutans Lindau leaves (CN) have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was teste...

  12. The Study of Apoptotic Effect of p-Coumaric Acid on Breast Cancer Cells MCF-7

    Directory of Open Access Journals (Sweden)

    M Kolahi

    2016-06-01

    Full Text Available Introduction: Polyphenolic compounds have anti proliferative and induced apoptotic features on cancer cells. p-Coumaric acid can be abundantly found in fruits, vegetables, plant production and honey. .  Breast cancer is the most frequently diagnosed cancer among women in the world. This study aimed to investigate the effect and mechanism of p- coumaric acid on apoptosis of MCF-7 breast cancer cells. Methods: In order to study appoptic effect of p- coumaric acid, MCF-7 breast cancer cells were treated with different concentrations of p- coumaric acid (10, 37, 70, 150 and 300 mM for 24 h. Cell viability was determined using MTT assay. Apoptosis markers including phosphatidylserine exposure at the outer leaflet of the plasma membrane were measured using flow cytometery for Annexin V affinity. Results: Cell viability of MCF-7 cells was decreased with increasing of p- coumaric acid concentration. Maximal effect of p- coumaric acid was observed in cells that treated with 300 mM for 24h (p< 0.05. Viability assay showed that the IC50 of p- coumaric acid in MCF-7 cells was about 40 mM. p- coumaric acid at dose of 300 mM significantly increased the late apoptotic cells with Annexin V+ and propium iodide (PI+ features after 24 h treatment. Conclusion: The results of this study showed that p- coumaric acid had effective appoptic activity against MCF-7 cells. The results can be helpful in understanding the anticancer mechanism of p- coumaric acid and using it was suggested as an alternative or complementary drug in cancer chemotherapy.

  13. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

    Institute of Scientific and Technical Information of China (English)

    Youn-Jung Kim; Hae-Jeong Park; Seo-Hyun Yoon; Mi-Ja Kim; Kang-Hyun Leem; Joo-Ho Chung; Hye-Kyung Kim

    2005-01-01

    AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

  14. Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

    Institute of Scientific and Technical Information of China (English)

    Long-Zhu Li; Hong-Xia Deng; Wen-Zhu Lou; Xue-Yan Sun; Meng-Wan Song; Jing Tao; Bing-Xiu Xiao; Jun-Ming Guo

    2012-01-01

    AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

  15. Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Aube, Michel, E-mail: 4aubem@videotron.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Larochelle, Christian, E-mail: christian.larochelle@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Ayotte, Pierre, E-mail: pierre.ayotte@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Laboratoire de Toxicologie, Institut national de sante publique du Quebec, 945 avenue Wolfe, Quebec, QC, Canada G1V 5B3 (Canada)

    2011-04-15

    Organochlorine compounds (OCs) are a group of persistent chemicals that accumulate in fatty tissues with age. Although OCs has been tested individually for their capacity to induce breast cancer cell proliferation, few studies examined the effect of complex mixtures that comprise compounds frequently detected in the serum of women. We constituted such an OC mixture containing 15 different components in environmentally relevant proportions and assessed its proliferative effects in four breast cancer cell lines (MCF-7, T47D, CAMA-1, MDAMB231) and in non-cancerous CV-1 cells. We also determined the capacity of the mixture to modulate cell cycle stage of breast cancer cells and to induce estrogenic and antiandrogenic effects using gene reporter assays. We observed that low concentrations of the mixture (100x10{sup 3} and 50x10{sup 3} dilutions) stimulated the proliferation of MCF-7 cells while higher concentrations (10x10{sup 3} and 5x10{sup 3} dilutions) had the opposite effect. In contrast, the mixture inhibited the proliferation of non-hormone-dependent cell lines. The mixture significantly increased the number of MCF-7 cells entering the S phase, an effect that was blocked by the antiestrogen ICI 182,780. Low concentrations of the mixture also caused an increase in CAMA-1 cell proliferation but only in the presence estradiol and dihydrotestosterone (p<0.05 at the 50x10{sup 3} dilution). DDT analogs and polychlorinated biphenyls all had the capacity to stimulate the proliferation of CAMA-1 cells in the presence of sex steroids. Reporter gene assays further revealed that the mixture and several of its constituents (DDT analogs, aldrin, dieldrin, {beta}-hexachlorocyclohexane, toxaphene) induced estrogenic effects, whereas the mixture and several components (DDT analogs, aldrin, dieldrin and PCBs) inhibited the androgen signaling pathway. Our results indicate that the complex OC mixture increases the proliferation of MCF-7 cells due to its estrogenic potential. The

  16. The effect of methylseleninic acid on paclitaxel efficacy in A2780 ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    Qiaoli Zhang; Rami G. Azrak

    2009-01-01

    Objective:The role of methylseleninic acid (MSeA), a selenium compound, has been documented in cancer chemoprevenfion. However, the therapeutic effect of MSeA in combination with paclitaxel, a chemotherapeutic agent used to treat ovarian cancer, is unknown. In this study, we investigated the effect of combination treatment of MSeA and paclitaxel against ovarian cancer cells. Methods:Ovarian cancer cells(A2780) were treated with different concentrations of MSeA, paclitaxel alone or in combination. The individual and combined concentrations of drugs that achieved certain cells growth/death were determined using a sulforhodamine B(SRB) assay. Drug effects on cell viability were further confirmed using floating cell count and trypan blue exclusion assay. The mean values, standard deviation were calculated and compared between treatment groups using unpaired t test. Results: The concentration of paclitaxel alone that inhibited 50% of cell growth(IC50) was 0.5 μmol/L. This concentration increased to 1.2 μmol/L when paclitaxel was given in sequential combination with MSeA. The number of dead cells after the combination treatment did not show a significance increase when compared with drug alone. Conclusion:Pretreatment with MSeA did not enhance the paclitaxel effect against A2780 ovarian cancex cells.

  17. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    Science.gov (United States)

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

  18. Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane

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    Berra Bruno

    2011-05-01

    Full Text Available Abstract Background PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells. Methods Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane. Results We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR. N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa. Conclusions Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

  19. KLF5 expression in prostate cancer tissue and effect of KLF5 knockdown on prostate cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Chong-Jun Shi; Wei-Zhong Yang; Yuan-Rong Kong; Wen-Guang Zhou

    2016-01-01

    Objective:To study the KLF5 expression in prostate cancer tissue and the effect of KLF5 knockdown on prostate cancer cell growth.Methods:Prostate cancer and benign prostatic hyperplasia tissue were collected to extract RNA and determine the mRNA levels ofKLF5as well as proliferation and epithelial-mesenchymal transition-related genes; DU145 cells were cultured and transfected with KLF5 siRNA and negative control siRNA, and then RNA was extracted to determine the mRNA levels of proliferation and epithelial-mesenchymal transition-related genes.Results:KLF5, SRSF1, Survivin, MACC1, c-Met, N-cadherinand Vimentin mRNA levels in prostate cancer tissue were significantly higher than those in benign prostatic hyperplasia tissue whileTGF-β,E-cadherinandβ-catenin mRNA levels were significantly lower than those in benign prostatic hyperplasia tissue;SRSF1, Survivin, MACC1, c-Met, TGF-β,N-cadherin andVimentinmRNA levels in si-KLF5 group were significantly lower than those in si-NC group while E-cadherin andβ-cateninmRNA levels were significantly higher than those in si-NC group.Conclusions: KLF5 expression levels are unusually high in prostate cancer tissue, and targeted knockdown of KLF5 expression can inhibit the prostate cancer cell proliferation and epithelial-mesenchymal transition.

  20. Blockade of sonic hedgehog signal pathway enhances antiproliferative effect of EGFR inhibitor in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Wei-guo HU; Tao LIU; Jiong-xin XIONG; Chun-you WANG

    2007-01-01

    Aim: To investigate the expression of sonic hedgehog (SHH) and epidermal growth factor receptor (EGFR) signal molecules in pancreatic cancer cells, and to assess the inhibitory effects through the blockade of the SHH and EGFR signaling path- ways by cyclopamine and Iressa, respectively. Methods: The expression of SHH and EGFR in pancreatic cancer cell lines (PANC-1, SUIT-2, and ASPC-1) was de-tected by RT-PCR and Western blot analysis. After treatment with different con-centrations of cyclopamine, alone or in combination with Iressa, the antiproliferative effect on pancreatic cancer cells was analyzed by methyl thiazolyl tetrazolium assays. A flow cytometry analysis was used to detect the cellular cycle distribu-tion and apoptosis of pancreatic cancer cells. Results: All of the 3 pancreatic cancer cell lines expressed SHH, Smoothened (SMO), and EGFR. Cyclopamine could downregulate the expression of EGFR in all cell lines. Cyclopamine or Iressa could induce a growth inhibitory effect in a dose-dependent manner. Moreover,the combined use of 2.5 μmol/L cyclopamine and 1 μmol/L Iressa induced an enhanced inhibitory effect and a greater apoptosis rate than any agent alone. The percentage of the cell population of the G0/G1 and sub-G1 phases was significantly increased along with the increasing dose of cyclopamine and/or Iressa. Conclusion: The blockade of the sonic hedgehog signal pathway enhances the antiproliferative effect of the EGFR inhibitor through the downregulation of its expression in pancreatic cancer cells. The simultaneous blockade of SHH and EGFR signaling represents possible targets of new treatment strategies for pan-creatic carcinoma.

  1. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

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    Liu Jun

    2004-07-01

    Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Methods Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53 and MKN-28 (mutant-type p53. RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. Results BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45, or in p53 mutant-type (MKN-28 gastric cancer cells. Conclusions The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

  2. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

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    Hartmann J

    2011-03-01

    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  3. The Biological Effect of Hepsin on the Proliferation and Invasion of PC-3 Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yong Xu; Zhiqiang Fan; Jantao Sun; Ranlu Liu; Weiming Zhao; Chunyu Wang; Ju Zhang

    2006-01-01

    OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells.METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells.RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC-3 cells. While the growth curve of the hepsin gene transfected PC-3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05).CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.

  4. Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3).

    Science.gov (United States)

    Kaplan, Fuat; Teksen, Fulya

    2016-03-01

    In this study, we studied the apoptotic and cytotoxic effects of salinomycin on human ovarian cancer cell line (OVCAR-3) as salinomycin is known as a selectively cancer stem cell killer agent. We used immortal human ovarian epithelial cell line (IHOEC) as control group. Ovarian cancer cells and ovarian epithelial cells were treated by different concentrations of salinomycin such as 0.1, 1, and 40 μM and incubated for 24, 48, and 72 h. Dimethylthiazol (MTT) cell viability assay was performed to determine cell viability and toxicity. On the other hand, the expression levels of some of the apoptosis-related genes, namely anti-apoptotic Bcl-2, apoptotic Bax, and Caspase-3 were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, Caspase-3 protein level was also determined. As a result, we concluded that incubation of human OVCAR-3 by 0.1 μM concentration of salinomycin for 24 h killed 40 % of the cancer cells by activating apoptosis but had no effect on normal cells. The apoptotic Bax gene expression was upregulated but anti-apoptotic Bcl-2 gene expression was downregulated. Active Caspase-3 protein level was increased significantly (p < 0.05).

  5. Antiproliferative and Apoptotic Effects of a Specific Antiprostate Stem Cell Single Chain Antibody on Human Prostate Cancer Cells

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    Foroogh Nejatollahi

    2013-01-01

    Full Text Available Prostate stem cell antigen (PSCA is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61% with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer.

  6. Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells.

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    Hakim, Luqman; Alias, Ekram; Makpol, Suzana; Ngah, Wan Zurinah Wan; Morad, Nor Azian; Yusof, Yasmin Anum Mohd

    2014-01-01

    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 5-FU against colorectal cancer.

  7. Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines.

    Science.gov (United States)

    Králová, Věra; Hanušová, Veronika; Staňková, Petra; Knoppová, Kateřina; Čáňová, Kristýna; Skálová, Lenka

    2013-10-01

    This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.

  8. Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells

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    Ganesh Radhakrishnan

    2012-09-01

    Full Text Available Abstract Background Arachidonic acid metabolite, generated by cyclooxygenase (COX, is implicated in the colorectal cancer (CRC pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2. Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. Methods Three colorectal cancer cell lines (HCA7, HT-29 & LoVo expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor and rofecoxib (COX-2 selective on prostaglandin E2 (PGE2 and leukotriene B4 (LTB4 secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. Results COX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P  Conclusions This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.

  9. Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

    Institute of Scientific and Technical Information of China (English)

    Nan-Hong Tang; Yan-Ling Chen; Xiao-Qian Wang; Xiu-Jin Li; Feng-Zhi Yin; Xiao-Zhong Wang

    2004-01-01

    AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells.METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-α, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR,respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment.RESULTS: In comparison with TNF-α inducing group, lipoASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37±1.56% to 14.23±1.07%, P<0.001). Meanwhile,cimetidine alone could inhibit the expression of E-selectin (36.37±1.56% vs 27.2±1.31%, P<0.001), but not ICAM-1 (69.34±2.50% vs68.07±2.10%,P>O.05)and the two kinds of mRNA, either. Compared with TNF-αα inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and Jipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups except for HepG2/ECV304 group (P >0.05).CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endothelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion.

  10. Expression of Some Genes Involved in Epigenetic in Breast Cancer Cell Lines: The Effect of Quercetin

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    fahime mohamadian

    2015-11-01

    Full Text Available Background & Objectives: Breast cancer is one of the most common cancers among women. Incorrect pattern of gene expression involved in epigenetic including APOBEC3B, DNMT-1, and TET-1 can develop breast cancer. Quercetin is a natural flavonoid with antioxidant and anti-cancer properties that have been reported in other studies. To investigate the effect mechanism of quercetin, this study examined the effect of quercetin on the expression of genes which were referred to in two classes of breast cancer cell lines. Materials & Methods: Cell lines including MCF-7 and MDA-MB-453 in separate boxes in the control group and the treated groups with two dosages of 50 and 100 mm of quercetin were cultured for 24 and 48 hours, respectively. RNA was extracted from the cells and then was converted to cDNA. Real-time PCR was used for APOBEC3B, DNMT_1, and TET-1 expression. Results: The results showed that quercetin had conflicting results after 24 hours in two cell lines as there was a decrease in the gene expression of APQBEC3B and an increase in that of DNMT-1 in MCF-7 cell line. In contrast, the cell line of MDA-MB-453, APOBEC3B, and DNMT-1 gene expression increased. While the 48-hour results showed that quercetin reduced the gene expression of APOBEC3B and DNMT-1 and increased that of the TET-1 in both cell lines. Conclusion: Due to the satisfactory effects of quercetin on breast cancer cells after 48 hours, these effects can be probably applied through epigenetic mechanisms. However, the final decision needs further investigation.

  11. Combined effects of lapatinib and bortezomib in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and activity of bortezomib against lapatinib-resistant breast cancer cells.

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    Ma, Chuandong; Niu, Xiuqing; Luo, Jianmin; Shao, Zhimin; Shen, Kunwei

    2010-10-01

    Lapatinib and bortezomib are highly active against breast cancer cells. Breast cancer patients who initially respond to lapatinib may eventually manifest acquired resistance to this treatment. Thus, the identification of novel agents that may prevent or delay the development of acquired resistance to lapatinib is critical. In the current study, we show that the combination of lapatinib and bortezomib results in a synergistic growth inhibition in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and that the combination enhances apoptosis of SK-BR-3 cells. Importantly, we found that the combination of lapatinib plus bortezomib more effectively blocked activation of the HER2 pathway in SK-BR-3 cells, compared with monotherapy. In addition, we established a model of acquired resistance to lapatinib by chronically challenging SK-BR-3 breast cancer cells with increasing concentrations of lapatinib. Here, we showed that bortezomib notably induced apoptosis of lapatinib-resistant SK-BR-3 pools and further inhibited HER2 signaling in the resistant cells. Taken together, the current data indicate a synergistic interaction between lapatinib and bortezomib in HER2-overexpressing breast cancer cells and provide the rationale for the clinical evaluation of these two noncross-resistant targeted therapies. The combination of lapatinib and bortezomib may be a potentially novel approach to prevent or delay the onset of acquired resistance to lapatinib in HER2-overxpressing/estrogen receptor (ER)-negative breast cancers.

  12. Effective cancer cell killing by hydrophobic nanovoid-enhanced cavitation under safe low-energy ultrasound.

    Science.gov (United States)

    Zhao, Yang; Zhu, Yingchun; Fu, Jingke; Wang, Lianzhou

    2014-03-01

    β-Cyclodextrin (β-CD)-capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low-energy ultrasound (≤1.0 W cm(-2) , 1 MHz). The water-dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low-energy ultrasound (≤1.0 W cm(-2) , 1 MHz). A significant cancer cell killing effect was observed in cancer cells and in a mouse xenograft tumor model treated with the nanoagents together with the low-energy ultrasound, showing a distinct dependence on the concentration of nanoagents and ultrasound intensity. By contrast, an antitumor effect was not observed when either low-energy ultrasound or nanoagents were applied alone. These findings are significant as the technique promises a safe, low-cost, and effective treatment for cancer therapy.

  13. Noxa enhances the cytotoxic effect of gemcitabine in human ovarian cancer cells.

    Science.gov (United States)

    Cao, Kang; Yang, Jing; Lin, Chao; Wang, Bao-ning; Yang, Yuan; Zhang, Jing; Dai, Jun; Li, Lei; Nie, Chun-lai; Yuan, Zhu; Li, Ming-yuan

    2012-05-01

    Noxa is an important proapoptotic protein in the intrinsic pathway of cell apoptosis. Experiments were carried out to investigate whether Noxa could, therefore, enhance the cytotoxic effect of gemcitabine in human ovarian cancer cell lines (A2780 and COC1). In this study, the combined treatment of Noxa and gemcitabine, in vitro, significantly inhibited the proliferation of A2780 and COC1 cells, as verified by MTT assay, Hoechst staining, and flow cytometric analysis. Moreover, the combination of Noxa and gemcitabine inhibited tumor growth and prolonged the survival of nude mice in vivo. The combined treatment also inhibited the growth of tumor xenografts through the inhibition of proliferation and the induction of apoptosis, as observed in immunohistochemical anti-PCNA staining and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Our data suggest that Noxa exhibited potent proapoptotic activity against human ovarian cancer cells, and the combination of Noxa and gemcitabine showed a more significant cytotoxic effect against ovarian cancer cells in comparison with either of these agents alone. To our knowledge, we have provided the first evidence that Noxa can enhance therapeutic responses of ovarian cancer cells to gemcitabine, and that it could be potentially useful as a chemosensitizer in ovarian cancer therapy.

  14. Effect of hydroxyapatite particle size, morphology and crystallinity on proliferation of colon cancer HCT116 cells

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Sangeeta; Das, Mitun, E-mail: mitun@cgcri.res.in; Balla, Vamsi Krishna

    2014-06-01

    The aim of the present work is to chemically and physically characterize the synthesized Hydroxyapatite (HAp) micro and nanoparticles and to explore the inhibitory effect of nano-HAps on the in vitro growth of human colon cancerous cells HCT116. HAp powder was synthesized using three different routes to achieve micro and nanosized powders, with different morphologies and crystallinity. The synthesized powders were characterized using X-ray diffraction, FTIR spectroscopy and scanning electron microscope. The results showed that the average crystallite size of HAp powder varies from 11 nm to 177 nm and respective crystallinity of powder found to be in the range of 0.12 and 0.92. The effect of these physico-chemical properties of HAp powders on human colon cancer HCT116 cells inhibition was determined in vitro. It was found that decreasing the HAp powder crystallite size between 11 nm and 22 nm significantly increases the HCT116 cell inhibition. Our results demonstrate that apart from HAp powder size their crystallinity and morphology also play an important role in cellular inhibition of human colon cancer cells. - Highlights: • Chemically synthesized hydroxyapatite micro and nano-particles with different morphologies and crystallinity. • In vitro cell–material interaction showed that hydroxyapatite nano-particles inhibit colon cancer cells. • Human colon cancer cell inhibition also depends on crystallinity and morphology of HAp powder.

  15. The cytotoxic effect of memantine and its effect on cytoskeletal proteins expression in metastatic breast cancer cell line

    Science.gov (United States)

    Seifabadi, Sima; Vaseghi, Golnaz; Javanmard, Shaghayegh Haghjooy; Omidi, Elham; Tajadini, Mohammadhasan; Zarrin, Bahareh

    2017-01-01

    Objective(s): Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine on breast cancer cell migration and proliferation, tau and stathmin gene expression in cancer cells and its synergistic effect with paclitaxel. Materials and Methods: The cell proliferation was evaluated by MTT assay and for this purpose, MCF-7 breast cancer cells were treated with various concentration of memantine (2, 20 and 100 μg/ml). Tau and stathmin mRNA expression was evaluated through quantitative real time RT-PCR method. The migration of cancer cells treated with memantine for 24 hr was compared to non-treated cells using an in vitro transmembrane migration assay. Results: Incubation of breast cancer cells with memantine resulted in a dose dependent reduction in cell survival (P=0.0001). Paclitaxel (100 nM) showed synergistic effect with memantine (P=0.0001). Memantine significantly decreased tau and stathmin mRNA expression (by RT-PCR), so that 100 µmol/l of memantine decreased tau and stathmin expression by 46% (P=0.0341) and 33% (P=0.043), respectively. Migration of cells was also decreased by memantine (P=0.0001). Conclusion: The presented data shows that memantine reduced mRNA levels of tau and stathmin proteins and also reduced cellular migration. PMID:28133523

  16. The cytotoxic effect of memantine and its effect on cytoskeletal proteins expression in metastatic breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Sima Seifabadi

    2017-01-01

    Full Text Available Objective(s:Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine on breast cancer cell migration and proliferation, tau and stathmin gene expression in cancer cells and its synergistic effect with paclitaxel.   Materials and Methods: The cell proliferation was evaluated by MTT assay and for this purpose, MCF-7 breast cancer cells were treated with various concentration of memantine (2, 20 and 100 μg/ml. Tau and stathmin mRNA expression was evaluated through quantitative real time RT-PCR method. The migration of cancer cells treated with memantine for 24 hr was compared to non-treated cells using an in vitro transmembrane migration assay. Results: Incubation of breast cancer cells with memantine resulted in a dose dependent reduction in cell survival (P=0.0001. Paclitaxel (100 nM showed synergistic effect with memantine (P=0.0001. Memantine significantly decreased tau and stathmin mRNA expression (by RT-PCR, so that 100 µmol/l of memantine decreased tau and stathmin expression by 46% (P=0.0341 and 33% (P=0.043, respectively. Migration of cells was also decreased by memantine (P=0.0001. Conclusion: The presented data shows that memantine reduced mRNA levels of tau and stathmin proteins and also reduced cellular migration.

  17. Effects of methylation status of caspase-8 promoter on antitumor activity of TRAIL to human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ru-gang; FANG Dian-chun; YANG Liu-qin; LUO Yuan-gang

    2004-01-01

    Objective: To study the effects of the methylation status of caspase-8 promoter on the antitumor activity of TRAIL to the human gastric cancer cells. Methods: The methylation of caspase-8 was measured with methylation specific PCR (MSP) and the antitomor capability of TRAIL to human gastric cancer cells was determined with MTT. Results: No methylation of caspase-8 in the human gastric cancer cells was found. The sensitivity of 5 lines of gastric cancer cells to the antitumor activity of TRAIL was different. The administration of the demethylation agent 5-Aza-2'-deoxycytidine ( 5-AzaCdR) increased the sensitivity of gastric cancer cells to TRAIL but did not change the methylation status of caspase-8 promoter in gastric cancer cells. Conclusion: 5-Aza-CdR increases the sensitivity of most of gastric cancer cells to TRAIL but caspase-8 is not involved in the antitumor activity of TRAIL.

  18. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Kobayashi, Alisa [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Maeda, Takeshi [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Fu, Qibin [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Oikawa, Masakazu [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yang, Gen, E-mail: gen.yang@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Konishi, Teruaki, E-mail: tkonishi@nirs.go.jp [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Uchihori, Yukio [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); and others

    2015-03-15

    Highlights: • Existence of radiation induced bystander effects (RIBE) between cancer stem-like cells (CSCs) and non stem-like cancer cells (NSCCs) in human fibrosarcoma HT1080 cells. • Existence of significant difference in generation and response of bystander signals between CSCs and NSCCs. • CSCs are significantly less sensitive to NO scavenger than that of NSCCs in terms of DNA double strand breaks induced by RIBE. - Abstract: Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy.

  19. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  20. Cytotoxicity Effects of Amoora rohituka and chittagonga on Breast and Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Leo L. Chan

    2011-01-01

    Full Text Available Chemotherapeutic agents for cancer are highly toxic to healthy tissues and hence alternative medicine avenues are widely researched. Majority of the recent studies on alternative medicine suggested that Amoora rohituka possesses considerable antitumor and antibacterial properties. In this work, rohituka and chittagonga, fractionated with petroleum ether, dichloromethane, and ethanol, were explored for their anticancer potential against two breast cancer (MCF-7 and HTB-126 and three pancreatic cancer (Panc-1, Mia-Paca2, and Capan1. The human foreskin fibroblast, Hs68, was also included. Cytotoxicity of each extract was analyzed using the MTT assay and label-free photonic crystal biosensor assay. A concentration series of each extract was performed on the six cell lines. For MCF-7 cancer cells, the chittagonga (Pet-Ether and CH2Cl2 and rohituka (Pet-Ether extracts induced cytotoxicity; the chittagonga (EtoAC and rohituka (MeOH extracts did not induce cytotoxicity. For HTB126, Panc-1, Mia-Paca2, and Capan-1 cancer cells, only the chittagonga CH2Cl2 extract showed a significant cytotoxic effect. The extracts were not cytotoxic to normal fibroblast Hs68 cells, which may be correlated to the specificity of Amoora extracts in targeting cancerous cells. Based on these results, further examination of the potential anticancer properties Amoora species and the identification of the active ingredients of these extracts is warranted.

  1. Effects of Curcuma longa Extract on Telomerase Activity in Lung and Breast Cancer Cells

    OpenAIRE

    Nosratollah Zarghami; Javad Ranjbari; Abbas Alibakhshi; Roghayeh Arezumand; Mohammad Pourhassan-Moghaddam; Mohammad Rahmati; Mohammad Mehdi Namvaran

    2014-01-01

    Background: The purpose of this study is to evaluate the effect of Curcuma longa extract on the telomerase gene expression in QU-DB lung cancer and T47D breast cancer cell lines. Materials and Methods: The present study is an experimental research. Using 3 different phases n-hexane, dichloromethane and methanol, total extract of Curcuma longa in a serial dilution was prepared and three phases was analyzed for determining which phase has more curcuminoids. Then the extract cytotoxicity effe...

  2. Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells

    Institute of Scientific and Technical Information of China (English)

    Chan Woo Cheon; Dae Hwan Kim; Dong Heon Kim; Yong Hoon Cho; Jae Hun Kim

    2009-01-01

    AIM: To determine the cytological and molecular effects of peroxisome proliferation-activated receptor (PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS: To determine the proliferation-suppressive effects of troglitazone and ciglitazone, SNU-216 and SNU-668 stomach cancer cells were plated in media containing 40 μmol/L troglitazone and ciglitazone at a density of 1 × 104 cells/well. After 3, 5 and 7 d, the cells were counted with a hemocytometer. To assess the appearance of PPAR-γ, a reverse-transcription polymerase chain reaction analysis was performed.On day 7, Western blotting was used to determine the effects of troglitazone and ciglitazone on the expression of p21 and phosphorylated-ERK ( pERK) genes. Flow cytometry analysis was used to determine which portion of the cell cycle was delayed when troglitazone was used to suppress cell proliferation. In order to clarify the mechanism underlying the activity of troglitazone, microarray analysis was conducted.RESULTS: PPAR-γ was manifested in both SNU-216and SNU-668 cells. Ciglitazone and troglitazone suppressed cell growth, and troglitazone was a stronger suppressor of stomach cancer cells than ciglitazone, an inducer of cell cycle arrest in the G1 phase. SNU-668 cells were also determined to be more sensitive to ciglitazone and troglitazone than SNU-216 cells. When troglitazone and ciglitazone were administered to stomach cancer cells, levels of p21 expression were increased, but ERK phosphorylation levels were reduced. When GW9662, an antagonist of PPAR-γ, was applied in conjunction with ciglitazone and troglitazone, the cell growth suppression effect was unaffected. The gene transcription program revealed a variety of alterations as the consequence of troglitazone treatment, and multiple troglitazoneassociated pathways were detected. The genes whose expression was increased by troglitazone treatment were associated with cell development, differentiation,signal transmission between cells, and

  3. Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Wang; Ke-Jian Guo; Bei-Ting Huang; Yong Liu; Xiao-Yun Tang; Jian-Jun Zhang; Qiang Xia

    2006-01-01

    AIM: To investigate the effect of telomerase hTERT gene antisense oligonucleotide (hTERT-ASO) on proliferation and telomerase activity of pancreatic cancer cell line Bxpc-3.METHODS: MTT assay was used to detect the effect of different doses of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the anti-tumor activity,the cells were divided into there groups: Control group (pancreatic cancer cell Bxpc-3); antisense oligonucleotide (hTERT-ASO) group; and nosense oligonucleotide group decorated with phosphorothioate. Telomerase activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined using flow cytometry assay.Cell apoptosis was observed by transmission electron microscope in each group.RESULTS: After treatment with 6 mmol/L hTERTASO, cell proliferation was inhibited in dose- and timedependent manner. The telomerase activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak appeared in front of G1 stage.CONCLUSION: Telomerase antisense oligodeoxynucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3 and decrease the telomerase activity and increase cell apoptosis rate in vitro.

  4. Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines.

    Science.gov (United States)

    Sharma, K; Pachauri, S D; Khandelwal, K; Ahmad, H; Arya, A; Biala, P; Agrawal, S; Pandey, R R; Srivastava, A; Srivastav, A; Saxena, J K; Dwivedi, A K

    2016-03-01

    Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential.

  5. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  6. Effect of survivin siRNA on biological behaviour of breast cancer MCF7 cells

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Yi-Feng Ye

    2015-01-01

    Objective:To investigate the expression of survivin in breast cancer cell lines and explore the effect of survivin siRNA on biology behavior of breast cancer cells.Methods: Western blot was performed to detect the expression of survivin in breast cancer cell lines. Eukaryotic expression vector pIRES2-EGFP-Survivin siRNA was constructed and transfected in MCF7 cells with liposome, the efficiency of survivin siRNA was measured by Western blot and RT-PCR. Cell proliferation and apoptosis were detected by CCK8 and cell flow respectively. Cell migration and invasion was measured by transwell assay.Results: Survivin was highly expressed in MCF-7. Green fluorescence was found in MCF-7 cells tranfected with survivin siRNA and control siRNA by inverted fluorescence microscopy, the protein and mRNA level of survivin was significantly lower in cells tranfected with survivin siRNA compared with control group. Compared with control group, interfering the expression of survivin by siRNA significantly decreased the proliferation, migration and invasion of MCF-7 cells, the percentage of apoptosis cells was greatly promoted.Conclusions: Interfering the expression of Survivin can inhibit the cell proliferation, migration and invasion, and promot apoptosis in MCF-7.

  7. Effects of cold atmospheric plasma generated in DI water on Cancer cells

    CERN Document Server

    Chen, Zhitong; Cheng, Xiaoqian; Gjika, Eda; Keidar, Michael

    2016-01-01

    Cold atmospheric plasma (CAP) has been shown to affect cells not only directly, but also by means of indirect treatment with previously prepared plasma stimulated solution. The objective of this study is to reveal the effects of plasma-stimulated media (PSM) on breast cancer cells (MDA-MB-231) and gastric cancer cells (NCl-N87). In our experiments, cold atmospheric plasma is generated in water using helium as carrier gas. The plasma generated in DI water during a 30-minute treatment had the strongest affect in inducing apoptosis in cultured human breast and gastric cancer cells. This result can be attributed to the presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in water during treatment.

  8. Antiproliferative effect of berberine on canine mammary gland cancer cell culture.

    Science.gov (United States)

    Sefidabi, Reyhaneh; Mortazavi, Pejman; Hosseini, Saeed

    2017-01-01

    Canine mammary gland tumors are the most frequent cause of cancer in female dogs. Numerous studies using cancer cell lines and clinical trials have indicated that various natural products and antioxidants reduce or possibly prevent the development of cancer. Berberine (BBR), the most important alkaloid in the Berberidaceae, which exerts a wide range of pharmacological and biochemical effects, has drawn much attention due to its particularly high antitumor activity in vitro and in animal studies. The aim of the present study was to investigate the antiproliferative effect of BBR against a canine mammary gland carcinoma cell line (CF41.Mg) in vitro. CF41.Mg cells were cultured in RPMI-1640 medium containing 10% heat inactived fetal bovine serum (FBS) and 100 mg/ml peniciline-streptomycin. Subsequently the cells were treated with different concentrations of BBR chloride (10, 25, 50, 100 and 200 µM) at a density of 12,000 cells/well in 96-well plates. Following treatment, the MTT assay was used to detect cell viability after 24-, 48- and 72-h incubations at 37°C with 5% CO2. The results indicated that BBR inhibited proliferation of canine mammary gland carcinoma cells, as treatment with 100 µM BBR for 24 h resulted in a significant decrease in cell viability (Pcancer cell death, it is proposed that BBR may serve as a candidate agent against canine mammary tumor cells via its antiproliferative activity.

  9. Effect of cyclin G2 on proliferative ability of prostate cancer PC-3 cell.

    Science.gov (United States)

    Cui, D W; Cheng, Y J; Jing, S W; Sun, G G

    2014-04-01

    This study aimed to analyze the expression, clinical significance of cyclin G2 (CCNG2) in prostate carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and Western blot were used to analyze CCNG2 protein expression in 85 cases of prostate cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were, respectively, transfected into prostate cancer PC-3 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA level and protein of CCNG2. MTT assay and cell cycle were also conducted as to the influence of the upregulated expression of CCNG2 that might be found on PC-3 cells biological effect. The level of CCNG2 protein expression was found to be significantly lower in prostate cancer tissue than normal tissues (P size (P lymph node metastasis, clinic stage, and Gleason score (P prostate cancer and correlated significantly with lymph node metastasis, clinic stage, and Gleason score, suggesting that CCNG2 may play important roles as a negative regulator to prostate cancer cell.

  10. Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition, and Apoptosis in Human Breast Cancer Cells.

    Science.gov (United States)

    Guo, Chih-Hung; Hsia, Simon; Shih, Min-Yi; Hsieh, Fang-Chin; Chen, Pei-Chung

    2015-01-01

    Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells.

  11. Fibroblasts weaken the anti-tumor effect of gefitinib on co-cultured non-small cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yong Xiao; Wang Peiqin; Jiang Tao; Yu Wenchen; Shang Yan; Han Yiping; Zhang Pingping

    2014-01-01

    Background Non-small cell lung cancer (NSCLC) is the most common lung malignancy worldwide.The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment,which consists of tumor cells,stroma,blood vessels,immune infiltrates and the extracellular matrix.Fibroblasts can produce numerous extraceilular matrix molecules and growth factors.Gefitinib has been evaluated as a first-line treatment in selected patients,and it has shown favorable efficacy especially in NSCLC,but it is not effective for everyone.Methods In this study,we examined the antitumor activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells.A series of co-culture experiments that employed cell counting kit-8 (CCK8),transwells,real-time polymerase chain reaction (RT-PCR) and Western blotting with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to learn more about tumor cell proliferation,migration and invasion; and to determine any change of epithelial mesenchymal transition (EMT)-associated tumor markers vimentin,matrix metallopro-teinase 2 (MMP2) and chemotaxis cytokines receptor 4 (CXCR4) mRNA levels.Results A549 cell proliferation in the presence of HFL-1 cells was not significantly increased compared with A549 cells alone,but A549 cell spheroid body formation was increased after co-culture,and treatment with gefitinib increased further.Our study also revealed that fibroblasts attenuated the lung cancer cell inhibition ratio of migration and invasion after gefitinib treatment in vitro.To further study this mechanism,RT-PCR analysis showed that vimentin,MMP2 and CXCR4 mRNA levels were more highly expressed in the lung cancer cells after co-culture,but did not obviously decrease compared with the control cells following gefitinib treatment.This suggests the mechanism by which fibroblasts attenuate gefitinib-induced expression of EMT-associated tumor markers.Finally,our results demonstrated that co-culture with A549 lung

  12. The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells.

    Science.gov (United States)

    Jaramillo, Sara; Lopez, Sergio; Varela, Lourdes M; Rodriguez-Arcos, Rocio; Jimenez, Ana; Abia, Rocio; Guillen, Rafael; Muriana, Francisco J G

    2010-10-27

    The aim of this study was to determine whether isorhamnetin, an immediate 3'-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells.

  13. Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Muhammad Yusran Abdul Aziz

    2016-09-01

    Full Text Available Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients.

  14. Effects of furanodiene on 95-D lung cancer cells: apoptosis, autophagy and G1 phase cell cycle arrest.

    Science.gov (United States)

    Xu, Wen-Shan; Li, Ting; Wu, Guo-Sheng; Dang, Yuan-Ye; Hao, Wen-Hui; Chen, Xiu-Ping; Lu, Jin-Jian; Wang, Yi-Tao

    2014-01-01

    Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Herein, we systematically investigated the effects of FUR on the significant processes of tumor progression with the relatively low concentrations in 95-D lung cancer cells. FUR concentration-dependently inhibited cell proliferation and blocked the cell cycle progressions in G1 phase by down-regulating the protein levels of cyclin D1 and CDK6, and up-regulating those of p21 and p27 in 95-D cells. FUR also affected the signaling molecules that regulate apoptosis in 95-D cells revealed by the down-regulation of the protein levels of full PARP, pro-caspase-7, survivin, and Bcl-2, and the up-regulation of cleaved PARP. Further studies showed that FUR enhanced the expression of light chain 3-II (LC3-II) in the protein level, indicating that autophagy is involved in this process. Besides, the adhesion ability of 95-D cells to matrigel and fibronectin was slightly inhibited after FUR treatment for 1 h in our experimental condition. FUR also slightly suppressed cell migration and invasion in 95-D cells according to the data from wound healing and Transwell assays, respectively. Taken together, FUR activated the signal molecules regulating G1 cell cycle arrest, apoptosis and autophagy, while slightly affecting the key steps of cell metastasis in 95-D lung cancer cells in the relatively low concentrations.

  15. Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

    Directory of Open Access Journals (Sweden)

    Zhang Yawei

    2009-08-01

    Full Text Available Abstract Background Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3 with cisplatin (DDP on A549 and H460 non-small cell lung cancer (NSCLC cells were explored. Methods A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT method, clonogenic assay, and flow cytometry (FCM. Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot. Results MTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The

  16. Effects of laminin glycopeptides on metastasis—related behaviors of cancer cells

    Institute of Scientific and Technical Information of China (English)

    JIANGXINNONG; ROULIZHOU; 等

    1998-01-01

    Our previous reports have shown that lamininglycopeptides (LN-GPs),the total glycopeptides prepared from laminin (LN),can prevent the experimental lung metastasis and liver metastasis of mouse cancer cells.In order to explore the anti-metastatic mechanism of LN-GPs,we studied the effects of LN-GPs on metastasisrelated behaviors of cancer cells in vitro.LN-GPs did not affect cell survival.However,LN-GPs inhibited cell attachment and spreading of S180 cells on LN-and Matrigelsubstrate in dose-dependent and time-dependent manners.Moreover,inhibition of cell attachment and spreading on Matrigel substrates were much greater on Matrigel substrate than on LN substrate.In the gresence of LN-GPs,S180 cells on LN substrate changed from a flattened polygonal shape to a round one,the migration of S180 cells on LN substrate decreased,and the number of a highly invasive human pulmonary giant carcinoma PG cells invading Matrigel filter in a Boyden chamber was reduced.LN-GPs thus have multiple inhibitory effects on cancer metastasisrelated behaviors.

  17. Kelussia odoratissima potentiates cytotoxic effects of radiation in HeLa cancer cell line

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    Azar Hosseini

    2017-02-01

    Full Text Available Objective: Cervical cancer is the second most common cause of death from cancer in women throughout the world. The aim of this study was to evaluate the cytotoxic activity of Kelussia odoratissima (K. odoratissima extract associated with radiotherapy in cervical cancer cells (HeLa cell line.Materials and Methods: Different concentration of the extract (25-500µg/ml was tested in HeLa cell lines. Cell cytotoxicity of the extract and the effects of the extract on radiation (2Gy/min-induced damages were assessed by MTT assay. Apoptosis was assessed using flow cytometric analysis.Result: K. odoratissima decreased cell viability in HeLa cell line in a concentration and time-dependent manner. When compared to the control,K. odoratissima induced a sub-G1 peak in the flow cytometry histogram of treated cells, indicating that apoptotic cell death is involved in K. odoratissima-induced toxicity. It was also shown that K. odoratissima sensitizes cells to radiation-induced toxicity.Conclusion: Our result showed the extract increased the radiation effect. This observation may be related to the presence of active compounds such as phthalides and ferulic acid.

  18. Kelussia odoratissima potentiates cytotoxic effects of radiation in HeLa cancer cell line

    Science.gov (United States)

    Hosseini, Azar; Saeidi Javadi, Shima; Fani-Pakdel, Azar; Mousavi, Seyed Hadi

    2017-01-01

    Objective: Cervical cancer is the second most common cause of death from cancer in women throughout the world. The aim of this study was to evaluate the cytotoxic activity of Kelussia odoratissima (K. odoratissima) extract associated with radiotherapy in cervical cancer cells (HeLa cell line). Materials and Methods: Different concentration of the extract (25-500µg/ml) was tested in HeLa cell lines. Cell cytotoxicity of the extract and the effects of the extract on radiation (2Gy/min)-induced damages were assessed by MTT assay. Apoptosis was assessed using flow cytometric analysis. Result: K. odoratissima decreased cell viability in HeLa cell line in a concentration and time-dependent manner. When compared to the control, K. odoratissima induced a sub-G1 peak in the flow cytometry histogram of treated cells, indicating that apoptotic cell death is involved in K. odoratissima-induced toxicity. It was also shown that K. odoratissima sensitizes cells to radiation-induced toxicity. Conclusion: Our result showed the extract increased the radiation effect. This observation may be related to the presence of active compounds such as phthalides and ferulic acid.

  19. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer and 4T1 (Breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Amir Ali Shahbazfar

    2014-01-01

    The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

  20. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro.

    Science.gov (United States)

    Tai, Joseph; Cheung, Susan; Wu, Matthew; Hasman, David

    2012-03-15

    Rosemary (Rosmarinus officinalis L.) is a popular culinary/medicinal herb. Recent studies have shown it has pharmacologic activities for cancer chemoprevention and therapy. This study evaluated the antiproliferation activity of rosemary extract (RE) against human ovarian cancer cells, and whether the extract and its three main active ingredients carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA) can enhance the antiproliferation activity of cisplatin (CDDP). Our study showed that RE has significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration) estimated at 1/1000 and 1/400 dilutions respectively. RE enhanced the antiproliferation effect with CDDP on both A2780 and A2780CP70 cells. A2780 cells were consistently more sensitive to CS, CA, and RA than A2780CP70 cells between 2.5 and 20μg/ml. CS and RA also showed synergistic antiproliferation effect with CDDP on A2780 cells at some concentrations. RE treated by ultrafiltration, dialysis, and removal of phenolics lost the antiproliferation activity suggested that the activity resides in phenolics with MW<1000Da. Apoptosis array study of A2780 cells treated with RE showed that the expression of a number of genes regulating apoptosis were modulated by the treatment. This study showed that RE inhibited the proliferation of ovarian cancer cell lines by affecting the cell cycle at multiple phases. It induced apoptosis by modifying the expression of multiple genes regulating apoptosis, and holds potential as an adjunct to cancer chemotherapy.

  1. Inhibition of human telomerase enhances the effect of chemotherapeutic agents in lung cancer cells.

    Science.gov (United States)

    Misawa, Masafumi; Tauchi, Tetsuzo; Sashida, Goro; Nakajima, Akihiro; Abe, Kenji; Ohyashiki, Junko H; Ohyashiki, Kazuma

    2002-11-01

    Telomerase is a ribonucleoprotein enzyme that maintains protective structures at the ends of eukaryotic chromosomes. Earlier studies have reported that the presence of telomerase activity in tumors of patients with non-small cell lung cancer patients correlates with a high proliferation rate and advanced pathological stage. Thus, the modification of telomerase activity may be a potential therapeutic modality for the treatment of lung and other cancers. We introduced vectors encoding dominant negative (DN)-hTERT, or wild-type (WT)-hTERT, or a control vector expressing only a drug-resistance marker, into the A549 lung cancer cell line, and assessed the biological effect of telomerase inhibition on cellular immortality. Ectopic expression of DN-hTERT resulted in complete inhibition of telomerase activity and reduction of telomere length. The entire population of telomerase-inhibited A549 cells exhibited cytoplasmic blebbling and chromatin condensation, which are features of apoptosis. In contrast, A549 cells expressing wild-type hTERT, which differs from the mutants by only two amino acids, exhibited normal morphology. Evidence for apoptosis in the telomerase-inhibited cells was provided by flow cytometric analysis with APO2.7 monoclonal antibody. We also observed enhanced induction of apoptosis by chemotherapeutic reagents, including cisplatin, docetaxel and etoposide, in DN-hTERT-expressing A549 cells, as compared with WT-hTERT-expressing cells. These results demonstrate that disruption of telomere maintenance limits the cellular lifespan of lung cancer cells, and show that the combined use of chemotherapeutic agents and telomere maintenance inhibition may be effective in the treatment of patients with non-small cell lung cancer.

  2. Inhibitory Effect of Sodium Selenite on Microsatellite Instability of RER+ Colorectal Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Investigation of the effects of sodium selenite on genetic instability of human tumor cells via its role in alteration of microsatellite sequence(MS) of RER+ (replication error) colon cancer cell line. Methods RER+ and RER- human colon cancer cell lines, RKO or SW480, were used as hosts for lipofection with pcmv-car in which a foreign(CA)14 repeat was inserted in the coding sequence of LacZ reporter gene, resulting in misreading LacZ frame. Any mutation which makes the base number of (CA)14 tract to be 3-fold will resume the normal reading frame of the reporter gene, and thus lead to expression and production of bioactive β-galactosidase. To test the effect of selenite on MI(microsatellite instability) of tumor cells, a series of concentrations of selenite were administered in cell culture in vitro. Variable expression of bioactive β-galactosidase of transfectant cells resulted from selenite administration was measured by A reading at λ410 after X-gal staining; Results Mutations of the exogenous(CA)14 developed and maintained in pcmv-car transfectant RKO cells but not in SW480 cells. It was found that blue cell frequency of RKO transfectant cells was markedly reduced after incubation of cells with 5 μmol/L of selenite for 5 days, at which concentration it was not toxic to cell growth. However, selenite at lower concentration of 1μmol/L didn′t exhibit suppression of blue cell rate until cell′s exposure to it for a longer period up to 5 weeks or more. Conclusion Our data showed that selenite displayed inhibitory effect on MI of human cancer cells and thus demonstrated its beneficial role in stabilization of human genomic DNA.

  3. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells

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    Zhang Fanjie

    2009-09-01

    Full Text Available Background: Accelerated glucose uptake for anerobic glycolysis is one of the major metabolic changes found in malignant cells. This property has been exploited for imaging malignancies and as a possible anticancer therapy. The nonmetabolizable glucose analog 2-deoxyglucose (2 DG interferes with glucose metabolism leading to breast cancer cell death. Aims: To determine whether 2DG can synergize with chemotherapeutic agents commonly used in breast cancer treatment and identify cellular characteristics associated with sensitivity to 2DG. Materials and Methods: SkBr3 breast cancer cells were incubated with varying concentrations of 5-fluorouracil (5FU, doxorubicin, cisplatin, cyclophosphamide, or herceptin with or without 2DG. Cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results: Combining 2DG with doxorubicin, 5 FU, cyclophosphamide, and herceptin resulted in enhanced cell death compared with each agent alone, while in combination with cisplatin, the amount of cell death was additive. Mouse embryo fibroblasts (MEF mutated for p53 (-/- were 30% more sensitive to the cytotoxic effects of 2DG than the parental cell lines. Cells mutated for Bax/Bac, genes involved in protection from apoptosis, are slightly more sensitive than the parental cell lines. Conclusions: These results indicate that 2DG acts synergistically with specific chemotherapeutic agents in causing cell death and the class of chemicals most sensitive appear to be those which cause DNA damage.

  4. Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Li-Ning Xu; Xin Wang; Sheng-Quan Zou

    2008-01-01

    AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in v/vo and in vitro,and to investigate the perspective of histone deacetylase inhibitor in its clinical application.METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-I cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay.A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-I cell line)was successfully established, and changes in the growth of transplanted tumor after treated with TSAwere measured.RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-I cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner.After the nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-I cell line) was successfully established, the growth of cancer was inhibited in the model, after treated with TSA.CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

  5. Multidirectional effects of triterpene saponins on cancer cells - mini-review of in vitro studies.

    Science.gov (United States)

    Koczurkiewicz, Paulina; Czyż, Jarosław; Podolak, Irma; Wójcik, Katarzyna; Galanty, Agnieszka; Janeczko, Zbigniew; Michalik, Marta

    2015-01-01

    Triterpene saponins (saponosides) are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflamatory, vasoprotective, gastroprotective and antimicrobial properties. Recently, a potential anticancer activity of saponins has been suggested by their cytotoxic, cytostatic, pro-apoptotic and anti-invasive effects. At high concentrations (more than 100 µM) saponins exert cytotoxic and haemolytic effects via permeabilization of the cell membranes. Noteworthy, the inhibition of cancer cell proliferation, the induction of apoptosis and attenuation of cell invasiveness is observed in the presence of low saponin concentrations. Saponins might affect the expression of genes associated with malignancy. These alterations are directly related to the invasive phenotype of cancer cells and depend on "cellular context". It illustrates the relationships between the action of saponins, and the momentary genomic/proteomic status of cancer cells. Here, we discuss the hallmarks of anti-cancer activity of saponins with the particular emphasis on anti-invasive effect of diverse groups of saponins that have been investigated in relation to tumor therapy.

  6. Blocking NOTCH Pathway can Enhance the Effect of EGFR Inhibitor through Targeting CD133+ Endometrial Cancer Cells.

    Science.gov (United States)

    Shang, Chao; Lang, Bin; Meng, Li-Rong

    2016-10-28

    ABSTACT Although the molecular therapeutics targeting key biomarkers such as epithelial growth factor receptor (EGFR), PI3K/AKT/mTOR, and vascular endothelial growth factor (VEGF) shows some success in clinical trials, some internally existing challenges in endothelial cancer biology hinder the drug effects. One of the major challenges stems from cancer stem cell-derived drug resistance. CD133 positive cells are well believed as cancer stem cells (CSC) in endometrial cancers and NOTCH pathway plays a critical role in retaining CD133+ cells by promoting CSC self-renewal and chemoresistance. Here, we initiated a therapeutic strategy to improve effects of EGFR inhibition by targeting NOTCH pathway of CD133+ cells in endometrial cancers. We first detected and purified the CD133+ cell fraction in endometrial cancer cell line Ishikawa (IK), and validated activation of NOTCH pathway in the CD133+ cells that have higher proliferation rate and lower apoptosis rate, comparing to CD133- cells. Results of nude mouse xenograft experiments further demonstrated CD133+ cells retain higher tumorigenesis capacity than CD133- cells, indicating their tumor-initiating property. Last, we applied both NOTCH inhibitor DAPT and EGFR inhibitor AG1478 treatment on endometrial cancer lines IK and HEC-1A and the results suggested improvement effects of the combination therapy compared to the treatments of DAPT or AG1478 alone. These findings indicated targeting NOTCH pathway in CD133+ cells, combining with EGFR inhibition, which provides a novel therapeutic strategy for endometrial cancer diseases.

  7. Effects of active bufadienolide compounds on human cancer cells and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells.

    Science.gov (United States)

    Yuan, Bo; He, Jing; Kisoh, Keishi; Hayashi, Hideki; Tanaka, Sachiko; Si, Nan; Zhao, Hai-Yu; Hirano, Toshihiko; Bian, Baolin; Takagi, Norio

    2016-09-01

    The growth inhibitory effects of bufadienolide compounds were investigated in two intractable cancer cells, a human glioblastoma cell line U-87 and a pancreatic cancer cell line SW1990. Among four bufadienolide compounds, a dose-dependent cytotoxicity was observed in these cancer cells after treatment with gamabufotalin and arenobufagin. The IC50 values of the two compounds were 3-5 times higher in normal peripheral blood mononuclear cells (PBMCs) than these values for both cancer cell lines. However, similar phenomena were not observed for two other bufadienolide compounds, telocinobufagin and bufalin. These results thus suggest that gamabufotalin and arenobufagin possess selective cytotoxic activity against tumor cells rather than normal cells. Moreover, a clear dose-dependent lactate dehydrogenase (LDH) release, a well-known hallmark of necrosis, was observed in both cancer cells treated with gamabufotalin, suggesting that gamabufotalin-mediated cell death is predominantly associated with a necrosis-like phenotype. Of most importance, treatment with as little as 8 ng/ml of gamabufotalin, even an almost non-toxic concentration to PBMCs, efficiently downregulated the percentages of CD4+CD25+Foxp3+ regulator T (Treg) cells in mitogen-activated PBMCs. Given that Treg cells play a critical role in tumor immunotolerance by suppressing antitumor immunity, these results suggest that gamabufotalin may serve as a promising candidate, as an adjuvant therapeutic agent by manipulating Treg cells to enhance the efficacy of conventional anticancer drugs and lessen their side-effects. These findings provide insights into the clinical application of gamabufotalin for cancer patients with glioblastoma/pancreatic cancer based on its cytocidal effect against tumor cells as well as its depletion of Treg cells.

  8. Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells.

    Science.gov (United States)

    Shao, Le-Ning; Zhu, Bao-Song; Xing, Chun-Gen; Yang, Xiao-Dong; Young, Wu; Cao, Jian-Ping

    2016-03-01

    Tumor‑associated macrophages (TAMs), a major component of the tumor microenvironment, are crucial to the processes of tumor growth, infiltration and metastasis, and contribute to drug resistance. The importance of TAMs in radiation resistance of colorectal cancer remains unclear. To investigate the effects of autophagy regulation of TAMs on the radiosensitivity of colorectal cancer cells, the current study induced TAM formation from THP‑1 monocyte cells. Sequential treatment of THP‑1 cells with PMA for 72 h and human recombinant interleukin‑4 for 24 h was used to stimulate THP‑1 differentiation to TAMs. Expression of the cell surface markers CD68, CD204 and CD206, and changes to cell morphology were used to confirm successful differentiation. The TAMs were stimulated to promote or inhibit autophagy during co‑culture with LoVo colorectal adenocarcinoma cells. The cells were irradiated, with subsequent measurement of LoVo colony formation and apoptosis. Additionally, the expression of p53, Bcl‑2, survivin and Smac proteins was assessed by western blotting. Monodansylcadaverin staining was used to analyze the presence of autophagic vacuoles in TAM, and western blot analysis was used to assess the expression of Beclin‑1, LC3B I and II, ATG‑3, ‑5 and ‑7. The results demonstrated TAM autophagy to be markedly altered by rapamycin and bafilomycin A1 treatment. Following co‑culture with TAMs, the colony formation rate and survival fraction of LoVo cells were significantly higher than those in the control group (PLoVo colorectal cancer cells. Upregulation of TAM autophagy using rapamycin exhibited more effective inhibition of LoVo colony formation than autophagy downregulation. Notably, apoptosis was significantly increased in LoVo cells when co‑cultured with TAMs only, or with rapamycin‑mediated autophagy upregulated TAMs, compared with LoVo cells cultured alone (PLoVo cells co‑cultured with TAMs, compared with the control group (P<0

  9. Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suzy [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Kwon, Eun Kyung; Lee, B. S.; Lee, Seung Hee; Park, B. S.; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-12-15

    Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according

  10. Effects of garlic oil on tumoragenecity and intercellular communication in human gastric cancer cell line

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Previous studies have demonstrated that garlic oil (GO) and its anti-tumor compound could inhibit DNA and RNA synthesis in human cancer cells.In order to explore the effects of garlic oil on carcinoma cells,a gastric carcinoma cell line,BGC-823 was studied at cellular and molecular levels after garlic oil treatment.Data showed that the cell differentiation and suppression of tumorigenicity were significantly induced in tumor cells after garlic oil treatment.There was a correlation between the cell-cell communication recovery and the increase of p53 and waf1/p21 gene expression in garlic oil-treated cells.This result suggested that tumor suppressor gene waf1/p21 and wt p53 might play an important role in this effect.

  11. Effects of garlic oil on tumoragenecity and intercellular communication in human gastric cancer cell line

    Institute of Scientific and Technical Information of China (English)

    李晓光; 谢锦玉; 李文梅; 季加孚; 崔建涛; 赵敏; 孙梅; 吕有勇

    2000-01-01

    Previous studies have demonstrated that garlic oil (GO) and its anti-tumor compound could inhibit DNA and RNA synthesis in human cancer cells. In order to explore the effects of garlic oil on carcinoma cells, a gastric carcinoma cell line, BGC-823 was studied at cellular and molecular levels after garlic oil treatment. Data showed that the cell differentiation and suppression of tumorigenicity were significantly induced in tumor cells after garlic oil treatment. There was a correlation between the cell-cell communication recovery and the increase of p53 and waf1/p21 gene expression in garlic oil-treated cells. This result suggested that tumor suppressor gene waf1/p21 and wt p53 might play an important role in this effect.

  12. Inhibitory effects of Leucaena leucocephala on the metastasis and invasion of human oral cancer cells.

    Science.gov (United States)

    Chung, Hsiao-Hang; Chen, Mu-Kuan; Chang, Yu-Chao; Yang, Shun-Fa; Lin, Chia-Chieh; Lin, Chiao-Wen

    2017-02-09

    Oral cancer is one of the most common cancers worldwide, and metastasis is recognized as a major factor causing its low survival rate. The inhibition of metastasis progress and the improvement of the survival rate for oral cancer are critical research objectives. Leucaena leucocephala from the mimosa branch Leucaena genus is native to Central and South America and has been used as a traditional remedy for treating various disorders. Previous studies have demonstrated antioxidant, anti-inflammatory as well as anticancer properties of L. leucocephala plant materials. However, the molecular mechanism underlying the anticancer effect induced by L. leucocephala remains unclear. In this study, we investigated the effect of L. leucocephala extract (LLE) on SCC-9 and SAS oral cancer cells and examined the potential inhibitory mechanisms involved. The results indicated that LLE attenuated the migration and invasion abilities of both SCC-9 and SAS cells by reducing the activity and protein expression of matrix metalloproteinases-2 (MMP-2). Regarding mitogen-activated protein kinase (MAPK) pathways, the phosphorylation of ERK1/2 and p38 exhibited a significant inhibitory effect in the presence of LLE. The application of ERK inhibitor and p38 inhibitor confirmed that both signalling transduction pathways were involved in the inhibition of cell metastasis. These data indicate that L. leucocephala could be a potent therapeutic agent for the prevention and treatment of oral cancer and a prominent plant source for anticancer research in the future.

  13. Anticarcinogenic effects of glycoalkaloids from potatoes against human cervical, liver, lymphoma, and stomach cancer cells.

    Science.gov (United States)

    Friedman, Mendel; Lee, Kap-Rang; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuke

    2005-07-27

    Methods were devised for the isolation of large amounts of pure alpha-chaconine and alpha-solanine from Dejima potatoes and for the extraction and analysis of total glycoalkaloids from five fresh potato varieties (Dejima, Jowon, Sumi, Toya, and Vora Valley). These compounds were then evaluated in experiments using a tetrazolium microculture (MTT) assay to assess the anticarcinogenic effects of (a) the isolated pure glycoalkaloids separately, (b) artificial mixtures of the two glycoalkaloids, and (c) the total glycoalkaloids isolated from each of the five potato varieties. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (Chang) cells. The results show that (a) the effects of the glycoalkaloids were concentration dependent in the range of 0.1-10 mug/mL (0.117-11.7 nmol/mL); (b) alpha-chaconine was more active than was alpha-solanine; (c) some mixtures exhibited synergistic effects, whereas other produced additive ones; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was generally lower than that of cancer liver cells. The decreases in cell populations were also observed visually by reversed-phase microscopy. The results complement related observations on the anticarcinogenic potential of food ingredients.

  14. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin......-layed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac® vaccine treatment in patients with progressive NSCLC....

  15. CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells.

    Science.gov (United States)

    Pervaiz, Asim; Ansari, Shariq; Berger, Martin R; Adwan, Hassan

    2015-05-01

    Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

  16. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  17. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  18. Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene.

    Science.gov (United States)

    Suganuma, Masami; Kurusu, Miki; Suzuki, Kaori; Tasaki, Emi; Fujiki, Hirota

    2006-07-01

    To more clearly understand the molecular mechanisms involved in synergistic enhancement of cancer preventive activity with the green tea polyphenol (-)-epigallocatechin gallate (EGCG), we examined the effects of cotreatment with EGCG plus celecoxib, a cyclooxygenase-2 selective inhibitor. We specifically looked for induction of apoptosis and expression of apoptosis related genes, with emphasis on growth arrest and DNA damage-inducible 153 (GADD153) gene, in human lung cancer cell line PC-9: Cotreatment with EGCG plus celecoxib strongly induced the expression of both GADD153 mRNA level and protein in PC-9 cells, while neither EGCG nor celecoxib alone did. However, cotreatment did not induce expression of other apoptosis related genes, p21(WAF1) and GADD45. Judging by upregulation of GADD153, only cotreatment with EGCG plus celecoxib synergistically induced apoptosis of PC-9 cells. Synergistic effects with the combination were also observed in 2 other lung cancer cell lines, A549 and ChaGo K-1. Furthermore, EGCG did not enhance GADD153 gene expression or apoptosis induction in PC-9 cells in combination with N-(4-hydroxyphenyl)retinamide or with aspirin. Thus, upregulation of GADD153 is closely correlated with synergistic enhancement of apoptosis with EGCG. Cotreatment also activated the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38 MAPK: Preteatment with PD98059 (ERK1/2 inhibitor) and UO126 (selective MEK inhibitor) abrogated both upregulation of GADD153 and synergistic induction of apoptosis of PC-9 cells, while SB203580 (p38 MAPK inhibitor) did not do so, indicating that GADD153 expression was mediated through the ERK signaling pathway. These findings indicate that high upregulation of GADD153 is a key requirement for cancer prevention in combination with EGCG.

  19. Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations.

    Science.gov (United States)

    Kim, Do-Hee; Kwak, Yeonui; Kim, Nam Doo; Sim, Taebo

    2016-01-01

    Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs.

  20. Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines.

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    Atmaca, Harika; Bozkurt, Emir

    2016-03-01

    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.

  1. The anti-cancer effect of Propranolol in K562 cell line: an in vitro study

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    S Bastani

    2016-03-01

    Full Text Available Introduction: Β-AR receptors are one of the proteins involved in cancer and stress. The therapeutic activity of β-blockers such as propranolol is attributed to the blockade of β1-adrenergic receptors (ARs. In this study, the effect of propranolol on the viability of K562 cell line was examined. Material and methods: In order to assessment of anti-tumoral effects of propranolol, different concentrations of propranolol were prepared. K562 cells were treated with different concentrations of propranolol, then the percentage of inhibitory effect of propranolol on K562 cell viability at different times (24, 48 and 72 hours was estimated by MTT assay. Gel electrophoresis of DNA and DAPI staining were used for apoptosis investigation. Statistical comparisons were performed using two-sample t-test, Nominal significance level of each univariate test was 0.05. Results: Propranolol decreased viability of K562 cell line. The inhibitory effect of propranolol is time- and concentration-dependent, thus in higher concentrations and 72 hours after treatment, the maximum inhibitory effect was observed. (P<0.05. As the results showed, Propranolol induces apoptosis in K562 cell line. Conclusions: With respect to the inhibitory effect of propranolol on cell viability and its apoptotic effect on K562 cell line, this drug may be used for cancer therapy.

  2. Effects of pharmacological ascorbate on hemoglobin-induced cancer cell proliferation.

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    Lu, Naihao; Ding, Yun; Tian, Rong; Yang, Zhen; Chen, Jianfa; Peng, Yi-Yuan

    2016-11-01

    The high heme content in red meat is associated with an increased risk of developing cancer. Pharmacologic concentrations of ascorbate can specifically kill a wide range of cancer cells. In this study, the impact of ascorbate at pharmacologic concentrations on hemoglobin (Hb)-modulated human hepatoma HepG2 cell survival was investigated. It was found that HepG2 cells were proliferated by Hb (5-25μM), but killed by high pharmacologic concentrations of ascorbate (2-10mM). Although ascorbate at the low pharmacologic concentration (0.5mM) alone exhibited insignificant effect on cell viability, it effectively inhibited Hb (10μM)-induced cancer cell proliferation. The mechanism of this cytotoxicity was based on the production of extracellular H2O2 and involved transition iron. The influence of ascorbate on Hb-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate) was further investigated to illustrate the reaction mechanism of ascorbate toxicity, where H2O2 was generated in the reaction of ascorbate with Hb. Furthermore, circular dichroism demonstrated no significant change in the secondary structure of Hb after ascorbate addition and molecular docking revealed binding modes of ascorbate with Hb. These results demonstrated that ascorbate could possess anti-cancer activity through interfering in Hb-dependent redox reactions.

  3. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells.

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    Sumit Arora

    Full Text Available Survival rates for patients with pancreatic cancer are extremely poor due to its asymptomatic progression to advanced and metastatic stage for which current therapies remain largely ineffective. Therefore, novel therapeutic agents and treatment approaches are desired to improve the clinical outcome. In this study, we determined the effects of honokiol, a biologically active constituent of oriental medicinal herb Magnolia officinalis/grandiflora, on two pancreatic cancer cell lines, MiaPaCa and Panc1, alone and in combination with the standard chemotherapeutic drug, gemcitabine. Honokiol exerted growth inhibitory effects on both the pancreatic cancer cell lines by causing cell cycle arrest at G₁ phase and induction of apoptosis. At the molecular level, honokiol markedly decreased the expression of cyclins (D1 and E and cyclin-dependent kinases (Cdk2 and Cdk4, and caused an increase in Cdk inhibitors, p21 and p27. Furthermore, honokiol treatment led to augmentation of Bax/Bcl-2 and Bax/Bcl-xL ratios to favor apoptosis in pancreatic cancer cells. These changes were accompanied by enhanced cytoplasmic accumulation of NF-κB with a concomitant decrease in nuclear fraction and reduced transcriptional activity of NF-κB responsive promoter. This was associated with decreased phosphorylation of inhibitor of kappa B alpha (IκB-α causing its stabilization and thus increased cellular levels. Importantly, honokiol also potentiated the cytotoxic effects of gemcitabine, in part, by restricting the gemcitabine-induced nuclear accumulation of NF-κB in the treated pancreatic cancer cell lines. Altogether, these findings demonstrate, for the first time, the growth inhibitory effects of honokiol in pancreatic cancer and indicate its potential usefulness as a novel natural agent in prevention and therapy.

  4. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

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    Ville Härmä

    Full Text Available The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D growth conditions using non-transformed prostate epithelial cells (EP156T, an androgen-sensitive prostate cancer cell line (LNCaP, and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  5. Antiproliferative effect of berberine on canine mammary gland cancer cell culture

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    Sefidabi, Reyhaneh; Mortazavi, Pejman; Hosseini, Saeed

    2017-01-01

    Canine mammary gland tumors are the most frequent cause of cancer in female dogs. Numerous studies using cancer cell lines and clinical trials have indicated that various natural products and antioxidants reduce or possibly prevent the development of cancer. Berberine (BBR), the most important alkaloid in the Berberidaceae, which exerts a wide range of pharmacological and biochemical effects, has drawn much attention due to its particularly high antitumor activity in vitro and in animal studies. The aim of the present study was to investigate the antiproliferative effect of BBR against a canine mammary gland carcinoma cell line (CF41.Mg) in vitro. CF41.Mg cells were cultured in RPMI-1640 medium containing 10% heat inactived fetal bovine serum (FBS) and 100 mg/ml peniciline-streptomycin. Subsequently the cells were treated with different concentrations of BBR chloride (10, 25, 50, 100 and 200 µM) at a density of 12,000 cells/well in 96-well plates. Following treatment, the MTT assay was used to detect cell viability after 24-, 48- and 72-h incubations at 37°C with 5% CO2. The results indicated that BBR inhibited proliferation of canine mammary gland carcinoma cells, as treatment with 100 µM BBR for 24 h resulted in a significant decrease in cell viability (P<0.005). As the present study demonstrated that BBR (10–200 µM) induced cancer cell death, it is proposed that BBR may serve as a candidate agent against canine mammary tumor cells via its antiproliferative activity.

  6. Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells.

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    Shah, Manisha H; Liu, Guei-Sheung; Thompson, Erik W; Dusting, Gregory J; Peshavariya, Hitesh M

    2015-04-01

    Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) have been implicated in development and progression of breast cancer. In the present study, we have evaluated the effects of the superoxide dismutase (SOD) mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 on superoxide and H2O2 formation as well as proliferation, adhesion, and migration of MCF-7 and MDA-MB-231 cells. Superoxide and H2O2 production was examined using dihydroethidium and Amplex red assays, respectively. Cell viability and adhesion were measured using a tetrazolium-based MTT assay. Cell proliferation was determined using trypan blue assay. Cell cycle progression was analyzed using flow cytometry. Clonal expansion of a single cell was performed using a colony formation assay. Cell migration was measured using transwell migration assay. Dual luciferase assay was used to determine NF-κB reporter activity. EUK 134 effectively reduced both superoxide and H2O2, whereas MnTmPyP removed superoxide but enhanced H2O2 formation. EUK 134 effectively attenuated viability, proliferation, clonal expansion, adhesion, and migration of MCF-7 and MDA-MB-231 cells. In contrast, MnTmPyP only reduced clonal expansion of MCF-7 and MDA-MB-231 cells but had no effect on adhesion and cell cycle progression. Tumor necrosis factor-alpha-induced NF-κB activity was reduced by EUK 134, whereas MnTmPyP enhanced this activity. These data indicate that the SOD mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 exert differential effects on breast cancer cell growth. Inhibition of H2O2 signaling using EUK 134-like compound might be a promising approach to breast cancer therapy.

  7. Apoptotic and genomic effects of corilagin on SKOV3 ovarian cancer cell line

    Science.gov (United States)

    Attar, Rukset; Cincin, Zeynep Birsu; Bireller, Elif Sinem; Cakmakoglu, Bedia

    2017-01-01

    Corilagin is a member of the tannin family and has been isolated from traditional Chinese medicinal plants, such as Phyllanthus spp. Corilagin has anti-inflammatory, antioxidative, antiatherogenic, and antihypertensive effects in various experimental models. In this research, we aimed to investigate for the first time whether corilagin had apoptotic and genomic effects in ovarian cancer treatment in the same study. The potential apoptotic of corilagin was investigated using a WST1 cell proliferation test, caspase 3, and mitochondrial membrane potential JC1 assays in a time- and dose-dependent manner. Genomic changes in expression levels against corilagin treatment were measured using an Illumina human HT-12V4 BeadChip microarray. Bioinformatic data analyses were performed using GenomeStudio and Ingenuity Pathway Analysis software. The data of our study demonstrated that there were statistically significant time- and dose-dependent increases in caspase 3 enzymatic activity and loss of mitochondrial membrane potential in line with decreases in cancer cell proliferation. According to gene-ontology analysis, we found that adherens junctions, antigen processing and presentation, and the phosphatidylinositol signaling system were the most statistically significant networks in response to corilagin treatment on SKOV3 cells, in a time- and dose-dependent manner. The apoptotic and genome-wide effects of corilagin on ovarian cancer cells were examined in detail for the first time in the literature. The results of our study suggest that corilagin might have the potential to be used as a new treatment option for epithelial ovarian cancer.

  8. Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells.

    Science.gov (United States)

    Kim, Dae-Hyun; Lee, Jae-Tae; Lee, In-Kyu; Ha, Jeoung-Hee

    2008-02-01

    This study examined the comparative anticancer effects of flavonoids and diazepam in the cultured cancer cells. In the SNU-C4 colorectal and MDA-MB-231 breast adenocarcinoma cells, apigenin and fisetin, flavonoids, and diazepam inhibited cancer cell survival concentration and incubation-time dependently. Diazepam consistently inhibited FAS activity, a known anticancer mechanism of flavonoids, in a concentration dependent manner. Unlike diazepam, in highly aggressive breast MDA-MB-231 cells known to have a nuclear/perinuclear located PBR, PK11195, a specific PBR ligand enhanced the proliferation of cells, and the proliferative effect of PK11195 was reversed by an addition of lovastatin, a HMG-CoA reductase inhibitor. Diazepam- and flavonoids-induced cytotoxic activity in both cancer cell lines was not reduced by the addition of 5-fluorouracil (5-FU), a chemotherapeutic agent. Like flavonoids, diazepam inhibited the release of vascular endothelial growth factor (VEGF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) into supernatants of cultured in the SNU-C4 and MDA-MB-231 cells. In conclusion, this study provided in vitro information on the safe use of sedative in oncologic patients.

  9. Effects of chemically modified nanostructured PLGA on functioning of lung and breast cancer cells

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    Zhang L

    2013-05-01

    Full Text Available Lijuan Zhang,1 Thomas J Webster21Department of Chemistry, 2School of Engineering, Brown University, Providence, RI, USABackground: The aim of this study was to investigate the effects of poly-lactic-co-glycolic acid (PLGA nanotopographies with alginate or chitosan protein preadsorption on the functioning of healthy and cancerous lung and breast cells, including adhesion, proliferation, apoptosis, and release of vascular endothelial growth factor (VEGF, which promotes tumor angiogenesis and secretion.Methods: We used a well established cast-mold technique to create nanoscale surface features on PLGA. Some of the nanomodified PLGA films were then exposed to alginate and chitosan. Surface roughness and the presence of protein was confirmed by atomic force microscopy. Surface energy was quantified by contact angle measurement.Results: Nanostructured PLGA surfaces with 23 nm features decreased synthesis of VEGF in both lung and breast cancer cells compared with conventional PLGA. Preadsorbing alginate further decreased cancer cell function, with nanostructured PLGA preadsorbed with alginate achieving the greatest decrease in synthesis of VEGF in both lung and breast cancer cells. In contrast, compared with nonmodified smooth PLGA, healthy cell functions were either not altered (ie, breast or were enhanced (ie, lung by use of nanostructured features and alginate or chitosan protein preadsorption.Conclusion: Using this technique, we developed surface nanometric roughness and modification of surface chemistry that could selectively decrease breast and lung cancer cell functioning without the need for chemotherapeutics. This technique requires further study in a wide range of anticancer and regenerative medicine applications.Keywords: breast, lung, cancer, nanotechnology, alginate, chitosan

  10. The Anticancer Effect of Fucoidan in PC-3 Prostate Cancer Cells

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    Hee-Kyoung Kang

    2013-08-01

    Full Text Available Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.

  11. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction.

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    Yen, Ching-Yu; Chiu, Chien-Chih; Haung, Rou-Wen; Yeh, Chi-Chen; Huang, Kuang-Jing; Chang, Kuo-Feng; Hseu, You-Cheng; Chang, Fang-Rong; Chang, Hsueh-Wei; Wu, Yang-Chang

    2012-09-18

    Goniothalamin (GTN), a plant bioactive styryl-lactone, is a natural product with potent anti-tumorigenesis effects for several types of cancer. Nonetheless, the anticancer effect of GTN has not been examined in oral cancer. The present study was designed to evaluate its potential anticancer effects in an oral squamous cell carcinoma (OSCC) model and to determine the possible mechanisms with respect to apoptosis, DNA damage, reactive oxygen species (ROS) induction, and mitochondrial membrane potential. Our data demonstrated that cell proliferation was significantly inhibited by GTN in Ca9-22 OSCC cancer cells in concentration- and time-dependent manners (pGTN-treated Ca9-22 cancer cells, the sub-G1 population and annexin V-intensity significantly increased in a concentration-dependent manner (pGTN-treated Ca9-22 cancer cells in concentration-response relationship (pGTN significantly induced intracellular ROS levels in Ca9-22 cancer cells in a concentration- and time-dependent manner (pGTN-treated Ca9-22 cancer cells was significantly decreased in concentration- and time-dependent relationships (pGTN against oral cancer cells is valid and GTN-induced growth inhibition and apoptosis influence the downstream cascade including ROS induction, DNA damage, and mitochondria membrane depolarization. Therefore, GTN has potential as a chemotherapeutic agent against oral cancer.

  12. The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Sheng-Qiang Yu; Kuo-Pao Lai; Shu-Jie Xia; Hong-Chiang Chang; Chawnshang Chang; Shuyuan Yeh

    2009-01-01

    The androgen receptor (AR) plays an important role in the development and progression of prostate cancer (PCa).Androgen deprivation therapy is initially effective in blocking tumor growth,but it eventually leads to the hormonerefractory state.The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear.Several PCa cell lines were established to study the role of AR in PCa,but the results were often inconsistent or contrasting in different cell lines,or in the same cell line grown under different conditions.The cellular and molecular alteration of epithelial cells and their microenvironments are complicated,and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR.In this paper,we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa.We also discuss the advantages of widely used epithelium-stroma co-culture systems,xenograft mouse models,and genetically engineered PCa mouse models.The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.

  13. Sesamin synergistically potentiates the anticancer effects of γ-tocotrienol in mammary cancer cell lines.

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    Akl, Mohamed R; Ayoub, Nehad M; Abuasal, Bilal S; Kaddoumi, Amal; Sylvester, Paul W

    2013-01-01

    γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of +SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability. However, sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism. Rather, combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability. Taken together, these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic, not cytotoxic, and results from G1 cell cycle arrest.

  14. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    Science.gov (United States)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-α) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  15. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

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    van Erk Marjan J

    2004-05-01

    Full Text Available Abstract Background Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. Methods Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours. Gene expression changes after short-term exposure (3 or 6 hours to curcumin were also studied in a second cell type, Caco-2 cells. Results Gene expression changes (>1.5-fold were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. Conclusions This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase

  16. Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells

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    Kaiyun Chen

    2016-05-01

    Full Text Available To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients’ treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

  17. Antitumour Effects of Isocurcumenol Isolated from Curcuma zedoaria Rhizomes on Human and Murine Cancer Cells

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    S. Lakshmi

    2011-01-01

    Full Text Available Curcuma zedoaria belonging to the family Zingiberaceae has been used in the traditional system of medicine in India and Southwest Asia in treating many human ailments and is found to possess many biological activities. The rationale of the present study was to isolate, identify, and characterize antitumour principles from the rhizomes of Curcuma zedoaria, to assess its cytotoxic effects on human and murine cancer cells, to determine its apoptosis inducing capacity in cancer cells, and to evaluate its tumour reducing properties in in vivo mice models. Isocurcumenol was characterized as the active compound by spectroscopy and was found to inhibit the proliferation of cancer cells without inducing significant toxicity to the normal cells. Fluorescent staining exhibited the morphological features of apoptosis in the compound-treated cancer cells. In vivo tumour reduction studies revealed that a dose of 35.7 mg/kg body weight significantly reduced the ascitic tumour in DLA-challenged mice and increased the lifespan with respect to untreated control mice.

  18. Antitumor Effects of Fucoidan on Human Colon Cancer Cells via Activation of Akt Signaling.

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    Han, Yong-Seok; Lee, Jun Hee; Lee, Sang Hun

    2015-05-01

    We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.

  19. Detecting the effect of targeted anti-cancer medicines on single cancer cells using a poly-silicon wire ion sensor integrated with a confined sensitive window.

    Science.gov (United States)

    Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Lin, Jing-Jenn

    2012-10-01

    A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

  20. Immune-dependent antineoplastic effects of cisplatin plus pyridoxine in non-small-cell lung cancer.

    Science.gov (United States)

    Aranda, F; Bloy, N; Pesquet, J; Petit, B; Chaba, K; Sauvat, A; Kepp, O; Khadra, N; Enot, D; Pfirschke, C; Pittet, M; Zitvogel, L; Kroemer, G; Senovilla, L

    2015-06-04

    cis-Diamminedichloroplatinum(II) (CDDP), which is mostly referred to as cisplatin, is a widely used antineoplastic. The efficacy of cisplatin can be improved by combining it with the vitamin B6 precursor pyridoxine. Here, we evaluated the putative synergistic interaction of CDDP with pyridoxine in the treatment of an orthotopic mouse model of non-small-cell lung cancer (NSCLC). CDDP and pyridoxine exhibited hyperadditive therapeutic effects. However, this synergy was only observed in the context of an intact immune system and disappeared when the otherwise successful drug combination was applied to the same NSCLC cancer implanted in the lungs of athymic mice (which lack T lymphocytes). Immunocompetent mice that had been cured from NSCLC by the combined regimen of CDDP plus pyridoxine became resistant against subcutaneous rechallenge with the same (but not with an unrelated) cancer cell line. In vitro, CDDP and pyridoxine did not only cause synergistic killing of NSCLC cells but also elicited signs of immunogenic cell death including an endoplasmic reticulum stress response and exposure of calreticulin at the surface of the NSCLC cells. NSCLC cells treated with CDDP plus pyridoxine in vitro elicited a protective anticancer immune response upon their injection into immunocompetent mice. Altogether, these results suggest that the combined regimen of cisplatin plus pyridoxine mediates immune-dependent antineoplastic effects against NSCLC.

  1. Effect of black raspberry extract in inhibiting NFkappa B dependent radioprotection in human breast cancer cells.

    Science.gov (United States)

    Madhusoodhanan, Rakhesh; Natarajan, Mohan; Singh, Jamunarani Veeraraghavan Nisha; Jamgade, Ambarish; Awasthi, Vibhudutta; Anant, Shrikant; Herman, Terence S; Aravindan, Natarajan

    2010-01-01

    Black raspberry extracts (RSE) have been shown to inhibit cancer cell growth and stimulate apoptosis. Also, studies have demonstrated that RSE inhibits transcriptional regulators including NFkappa B. Accordingly, we investigated the effect of RSE in inhibiting radiation (IR) induced NFkappa B mediated radioprotection in breast adenocarcinoma cells. MCF-7 cells were exposed to IR (2Gy), treated with RSE (0.5, 1.0, 2.0 micro g/ml) or treated with RSE (1.0 micro g/ml) followed by IR exposure, and harvested after 1, 3, 6, 24, 48, and 72 h. NFkappa B DNA-binding activity was measured by EMSA and phosphorylated Ikappa Balpha by immunoblotting. Expression of IAP1, IAP2, XIAP and survivin were measured by QPCR and immunoblotting. Cell survival was measured using MTT assay and cell death using Caspase-3/7 activity. Effect of RSE on IR induced MnSOD, TNFalpha, IL-1alpha and MnSOD activity was also determined. RSE inhibited NFkappa B activity in a dose-dependent manner. Also, RSE inhibited IR-induced sustained activation of NFkappa B, and NFkappa B regulated IAP1, IAP2, XIAP, and survivin. In addition, RSE inhibited IR-induced TNFalpha, IL-1alpha, and MnSOD levels and MnSOD activity. RSE suppressed cell survival and enhanced cell death. These results suggest that RSE may act as a potent radiosensitizer by overcoming the effects of NFkappa B mediated radioprotection in human breast cancer cells.

  2. Inhibitory effect of Polo-like kinase 1 depletion on mitosis and apoptosis of gastric cancer cells

    OpenAIRE

    Chen, Xue-Hua; Lan, Bin; Qu, Ying; ZHANG, XIAO-QING; Cai, Qu; Liu, Bing-Ya; Zhu, Zheng-Gang

    2006-01-01

    AIM: Polo-like kinase 1 (PLK1) serine/threonine kinase plays a vital role in multiple phases of mitosis in gastric cancer cells. To investigate the effect of PLK1 depletion on mitosis and apoptosis of gastric cancer cells.

  3. Cadmium influences the 5-fluorouracil cytotoxic effects on breast cancer cells

    Science.gov (United States)

    Asara, Y.; Marchal, J.A.; Bandiera, P.; Mazzarello, V.; Delogu, L.G.; Sotgiu, M.A.; Montella, A.; Madeddu, R.

    2012-01-01

    The aim of the research was to evaluate a heavy metal, cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-fluorouracil (5-FU), after exposure to different concentrations of cd. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 µM) to the cells treated with Cd (5 µM–20 µM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer. PMID:22472887

  4. Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells

    Directory of Open Access Journals (Sweden)

    Y. Asara

    2012-01-01

    Full Text Available The aim of the research was to evaluate a heavy metal, Cadmium (Cd, which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-Fluorouracil (5-FU, after exposure to different concentrations of Cadmium. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 μM to the cells treated with Cd (5 μM-20 μM did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer.

  5. Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells.

    Science.gov (United States)

    Asara, Y; Marchal, J A; Bandiera, P; Mazzarello, V; Delogu, L G; Sotgiu, M A; Montella, A; Madeddu, R

    2012-01-20

    The aim of the research was to evaluate a heavy metal, Cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-Fluorouracil (5-FU), after exposure to different concentrations of Cadmium. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 μM) to the cells treated with Cd (5 μM-20 μM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer.

  6. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Yanxi [Department of Biology, Lakehead University, Thunder Bay (Canada); College of Life Science, Shanxi University, Taiyuan (China); Wu, Bo [Department of Biology, Lakehead University, Thunder Bay (Canada); Department of Pathophysiology, Harbin Medical University, Harbin (China); Cao, Qiuhui [Department of Biology, Lakehead University, Thunder Bay (Canada); Wu, Lingyun [Department of Pathophysiology, Harbin Medical University, Harbin (China); Department of Pharmacology, University of Saskatchewan, Saskatoon (Canada); Yang, Guangdong, E-mail: gyang@lakeheadu.ca [The School of Kinesiology, Lakehead University, Thunder Bay (Canada)

    2011-12-15

    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

  7. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Macedo, Taysa B.C.; Torres, Hianne M.; Yamamoto-Silva, Fernanda Paula; Silva, Maria Alves G. [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Escola de Odontologia; Elias, Silvia T.; Silveira, Damaris; Magalhaes, Perola O.; Lofrano-Porto, Adriana; Guerra, Eliete N.S., E-mail: elieteneves@unb.br [Universidade de Brasilia (UnB), Brasilia, DF (Brazil). Faculdade de Ciencias da Saude

    2016-01-15

    The mouth and oropharynx cancer is the 6{sup th} most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  8. The Effect of Curcumin on Proliferation and Apoptosis in LNCaP Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Lianying Zhang; Lijun Chen; Bin Meng; Jiangrui Suo; Hongmin Wang; Hong Xie; Qiuyue Jin; Li Yao; Ruimin Wang

    2006-01-01

    OBJECTIVE To observe the effect of curcumin on proliferation and apoptosis in the prostate cancer LNCaP cell line.METHODS The AXSYMTM system luciferase method was used to examine the effect of various concentratious of curcumin on the content of prostate specific antigen (PSA) in prostate cancer LNCaP cells. A pGL3-PSA luciferase expression vector, containing 640 bp DNA of the PSA gene 5'-promoter region was constructed and transfected into the LNCaP cells with lipofectin. By measuring luciferase activity, the effect of 10 μmol/L, 20 μmol/L, 30 and 40 μmol/L curcumin on the promoter was studied. Effects on cell growth and apoptosis were analyzed by microscopy, the MTT colorimetric assay and flow cytometry Western-blotting was used to measure expression of the androgen receptor (AR) in the LNCaP cells treated with different concentrations of curcumin.RESULTS The results showed that the expression of PSA was inhibited as curcumin reduced the activity of luciferase. Curcumin also caused a sigificant concentration-dependent decrease in AR expession measured by Western-blotting. Cell growth was inhibited and apoptosis was induced.CONCLUSION By inhibiting AR expression, curcumin reduced the function of the PSA promoter and inhibited PSA protein expression. Curcumin decreased the cellular proliferation and induced apoptosis in LNCaP cells in a concention-dependent manner.

  9. Effects of Radiation on Proteasome Function in Prostate Cancer Cells

    Science.gov (United States)

    2009-02-01

    Transcription ribosomal protein L19, L24l L26, L27a, S13, S3a similar to 40S ribosomal protein SA ( p40 ) (34/67 kDa laminin receptor...mM ATP, 0.2% [vol/vol] Nonidet P-40 and 20% glycerol) were added to the cells, and the mixtures were vortexed for 1 minute. Beads and cell debris

  10. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    Science.gov (United States)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-01

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/μm) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows ˜ 28% reduction of 12C6+ ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  11. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha [Inter University Accelerator Centre, Aruna Asaf Ali Marg, Post box-10502, New Delhi-110067 (India)

    2013-07-18

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/{mu}m) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows {approx} 28% reduction of {sup 12}C{sup 6+} ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  12. EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    郑华川; 杨雪飞; 孙晋民; 李晓晗; 姜卫国; 张荫昌; 辛彦

    2003-01-01

    Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren's classification, histological classification (P0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

  13. Anti-proliferation Effect of Polypeptide Extracted from Scorpion Venom on Human Prostate Cancer Cells in vitro

    OpenAIRE

    Zhang, Yue Ying; Wu, Li Cun; Wang, Zhao Peng; Wang, Zhao Xia; Jia, Qing; Jiang, Guo Sheng; Zhang, Wei Dong

    2009-01-01

    Background Prostate cancer is a major cause of cancer-related death in men. Therefore there has been considerable interest to explore neoadjuvant therapy. Polypeptide extracted from scorpion venom (PESV), originally obtained from the East-Asian scorpion Buthus martensi Karsch (BmK), is being studied for both prevention and treatment of various human malignancies including prostate cancer. Methods The present study was to investigate the effect of PESV on cell proliferation, cell cycle, and ap...

  14. The pro-adhesive and pro-survival effects of glucocorticoid in human ovarian cancer cells.

    Science.gov (United States)

    Yin, Lijuan; Fang, Fang; Song, Xinglei; Wang, Yan; Huang, Gaoxiang; Su, Jie; Hui, Ning; Lu, Jian

    2016-07-01

    Cell adhesion to extracellular matrix (ECM) is controlled by multiple signaling molecules and intracellular pathways, and is pivotal for survival and growth of cells from most solid tumors. Our previous works demonstrated that dexamethasone (DEX) significantly enhances cell adhesion and cell resistance to chemotherapeutics by increasing the levels of integrin β1, α4, and α5 in human ovarian cancer cells. However, it is unclear whether the components of ECM or other membrane molecules are also involved in the pro-adhesive effect of DEX in ovarian cancer cells. In this study, we demonstrated that the treatment of cells with DEX did not change the expression of collagens (I, III, and IV), laminin, CD44, and its principal ligand hyaluronan (HA), but significantly increased the levels of intracellular and secreted fibronectin (FN). Inhibiting the expression of FN with FN1 siRNA or blocking CD44, another FN receptor, with CD44 blocking antibody significantly attenuated the pro-adhesion of DEX, indicating that upregulation of FN mediates the pro-adhesive effect of DEX by its interaction with CD44 besides integrin β1. Moreover, DEX significantly enhanced cell resistance to the chemotherapeutic agent paclitaxel (PTX) by activating PI-3K-Akt pathway. Finally, we found that DEX also significantly upregulated the expression of MUC1, a transmembrane glycoprotein. Inhibiting the expression of MUC1 with MUC1 siRNA significantly attenuated the DEX-induced effects of pro-adhesion, Akt-activation, and pro-survival. In conclusion, these results provide new data that upregulation of FN and MUC1 by DEX contributes to DEX-induced pro-adhesion and protects ovarian cancer cells from chemotherapy.

  15. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

  16. Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.

    Science.gov (United States)

    Peng, Gong-ling; Tian, Ye; Lu, Chong; Guo, Hui; Zhao, Xiang-wang; Guo, Ya-wen; Wang, Long-qiang; Du, Qiu-li; Liu, Chun-ping

    2014-04-01

    This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

  17. Effects of emodin on gene expression profile in small cell lung cancer NCI-H446 cells

    Institute of Scientific and Technical Information of China (English)

    FU Zhong-yan; HAN Jin-xiang; HUANG Hai-yan

    2007-01-01

    Background The treatment of patients with small cell lung cancer (SCLC) is based on chemotherapy. However, the treatment is limited by the development of drug resistance. Emodin has been shown to exhibit an anti-cancer effect. But the molecular mechanism remains unclear. This study was conducted to investigate the effect of emodin on the gene expression profile changes in SCLC NCI-H446 cells.Methods NCI-H446 cells were treated with emodin and cell viability was determined by MTT assay. Cell apoptosis was determined by both flow cytometry and caspase-3 activity assay. The effect of emodin on the gene expression profile of NCI-H446 cells was analyzed using cDNA microarray. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to validate the microarray results.Results Emodin suppressed viability, induced apoptosis and changed cell cycle of NCI-H446 cells. Among the 1262 genes, 10 genes were up-regulated and 8 genes were down-regulated more than 2 folds in NCI-H446 cells when compared with the control cells after treatment with emodin for 12 hours, while 12 genes were up-regulated and 24 genes were down-regulated after treatment with emodin for 24 hours. These genes were involved in metabolism, signal transduction, transcription regulation, cytoskeleton organization, immune response, transport, protein synthesis, cell cycle control, cell adhesion and RNA processing. The RT-PCR results were consistent with those obtained by the microarray.Conclusions Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.

  18. Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Singh Rakesh K

    2010-02-01

    Full Text Available Abstract Background Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC, including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19. Methods Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS Results HNTMB displayed high cytotoxicity (IC50 200-400 nM compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM. In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM. In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels. Conclusions The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other

  19. Azurin as Antitumor Protein and its Effect on the Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Mervat S. Mohamed

    2010-11-01

    Full Text Available As a low molecular weight redox protein was elaborated from the pathogenic bacteria Pseudomonas aeruginosa, azurin is one of the representative bacterial products used in the treatment of tumours. In this study, Pseudomonas aeruginosa was isolated from lungs of cystic fibrosis patients in Egypt, and identified by 16S rRNA. Azurin gene was amplified using the suitable PCR programme. The gene was cloned into pGEM-T easy vector and sequenced. Then subcloned into the overexpression vector pET-28a (+ using E. coli BL21 as expression bacteria. The SDS-PAGE analysis showed that the gene overexpressed in E. coli. The recombinant protein was purified by one step purification using Ni++ resin. The effect of azurin on proliferation and apoptosis of human breast cancer cell line (MCF7, human hepatocellular carcinoma cell line (HEPG2 and human colon carcinoma cell line (HCT116 and human normal melanocytes (HFB4 cell line was studied. The results showed that azurin strongly inhibited the proliferation of both colon carcinoma cell line and breast cancer cell line. Whereas unclear result of the effect of azurin on hepatocellular carcinoma cell line was exhibited. At the same time, azurin didn’t show any effect on the human normal melanocytes.

  20. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells.

    Science.gov (United States)

    Huo, Jian

    2016-08-01

    To observe the changes in invasion capacity of gastric cancer BGC823 cells after being treated with chitosan-encapsulated BRAF siRNA nanoparticles, and to evaluate the effects of the nanoparticle-mediated BRAF siRNA interference on cell invasion and metastasis, BRAF siRNA was encapsulated with chitosan into nanoparticles sized 350 nm to treat gastric cancer cells. Silencing of BRAF was detected by Western blot and PCR, and cell invasion was observed by the Transwell assay. The nanoparticles significantly downregulated BRAF expression in BGC823 cells (P Chitosan nanoparticle-mediated BRAF siRNA interference evidently reduced the invasion capacity of gastric cancers.

  1. Effects of Radiation on Proteasome Function in Prostate Cancer Cells

    Science.gov (United States)

    2012-02-01

    vol/vol] Nonidet P - 40 and 20% glycerol) were added to the cells, and the mixtures were vortexed for 1 minute. Beads and cell debris were removed by...20 40 60 80 G1 S G2/M % o f t ot al p op ul at io n PC3 0 2 4 6 8 10 0.01 0.1 1 Non-stopped 0h 6h Dose (Gy) Su rv iv in g fr ac tio n Fig. 1...between 0 and 40 %, suggesting that proteasomes are far more dynamic than we initially thought. A major discovery in year 2 and 3 was the

  2. Effects of chitin and its derivatives on human cancer cells lines.

    Science.gov (United States)

    Bouhenna, M; Salah, R; Bakour, R; Drouiche, N; Abdi, N; Grib, H; Lounici, H; Mameri, N

    2015-10-01

    The present study is focused on the effect of chitin derivatives against human cancer cell lines RD and Hep2. As an outcome from this research, chitin was cytotoxic at IC50 = 400 μg/ml and 200 μg/ml against Hep2 cells and RD cells lines, respectively. Irradiated chitin had an IC50 value of 450 μg/ml for Hep2 and an IC50 of 200 μg/ml for RD. The lowest IC50 is attributed to chitosan, 300 μg/ml in Hep2 and 190 μg/ml in RD.

  3. Effects of TRPC6 on invasibility of low-differentiated prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Xiang Li; Jing Liu; Jun Li; Li-Jun Li; Ming-Xing Qiu

    2014-01-01

    Objective: To study the expression of TRPC6 among prostate cancer cells, establish high expression cell lines of TRPC6, and to provide potential cell mode for prostate cancer oncogenesis and development. Methods: Occurrence and development of prostate cancer cells, PC3, PC-3 m DU145, 22 rv1, LNCaP and normal prostate epithelial cells in the PrEC TRPC6 expression level were detected by QPCR method. Calcium phosphate transfection method was used to package retrovirus pLEGFP-N1-TRPC6 and pLEGFP-N1-vector and infect the prostate cancer cells, a stable high expression of TRPC6 prostate cancer cells. Sable cell lines of TRPC6, matrix metalloproteinase (MMP) 2, MMP9 expression was detected by QPCR and Western blot. Change of cell invasion ability was detected by Transwell. Results: The expression level of prostate cancer cells TRPC6 were higher than control group PrEC cells. Among TPRC6 the expression of cell line PC 3 transfer potential wre the lowest, and high transfer cell line PC-3M express was the highest. Real-time fluorescent quantitative PCR and western blot results showed that after filter, the seventh generation of cell TRPC6 protein and mRNA expression levels were higher than the control group obviously. Transwell experimental results showed that the overexpression of TRPC6 could promote the invasion ability of PC3 prostate cancer cells. Conclusions: TRPC6 expressed in prostate cancer cells is in disorder, and its action may be associated with the invasion and metastasis of prostate cancer cells; successful establishment of stable high expression of TRPC6 prostate cancer cells primarily confirm the invasion-trigger ability of TRPC6 on prostate cancer, and lay down the foundation for exploring the TRPC6’s role in the occurrence and development of prostate cancer mechanism.

  4. THE CYTOTOXIC EFFECTS OF CRUDE BILE ON HUMAN PANCREATIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To identify effects of bile acids on pancreatic cancer, The ultrastructure and growth of PANC-1 and MIA PaCa-2 cell lines in crude bile modified medium were studied. Methods The growth of PANC-1 and MIA PaCa-2 cells in RPMI 1640 with or without 1%, 2% and 4% of the purified crude bile (containing total bile acids 10.17mmol/L) was assessed for 2, 4, 6, 8d by using MTT assay to determine inhibitory rate. The cell surface and intracellular ultrastructure of PANC-1 cells was investigated by SEM and TEM at 24h and 48h, respectively. Re sults The proliferation of both cell lines in bile treated medium were greatly retarded (P <0.001). The inhibitory rate of 1%, 2% and 4% bile on Panc-1 cells in 4d were 38%, 60% and 66%, respectively (P <0. 05), on MIA PaCa-2 cells at 4d were 28%, 39% and 52%, respectively (P <0. 05). The cells grown in bile for 48h lost their mi crovilli, their mitochondria and other organelles became vacuolated. Conclusion The bile acids in bile has cytotoxicity on PANC-1 and MIAPACA-2 cells, which may inhibit pancreatic cancer progress in patients clinically.

  5. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    Science.gov (United States)

    Ishaq, M.; Bazaka, K.; Ostrikov, K.

    2015-12-01

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  6. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishaq, M., E-mail: ishaqmusarat@gmail.com [Peter MacCallum Cancer Centre, East Melbourne, VIC 3002 (Australia); Comonwealth Scientific and Industrial Research Organization, Sydney, New South Wales (Australia); Bazaka, K. [Institute for Health and Biomedical Innovation, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000 (Australia); Ostrikov, K. [Comonwealth Scientific and Industrial Research Organization, Sydney, New South Wales (Australia); Institute for Health and Biomedical Innovation, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000 (Australia)

    2015-12-15

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  7. Effect of polyclonal activators on cytokine production by blood cells and by malignant breast cancer cells.

    Science.gov (United States)

    Kunts, T A; Karpukhina, K V; Mikhaylova, E S; Marinkin, I O; Varaksin, N A; Autenshlyus, A I; Lyakhovich, V V

    2016-01-01

    The production of cytokines by peripheral blood cells and biopsy specimens of tumors stimulated by polyclonal activators (PAs) was evaluated in 34 patients with invasive ductal breast carcinoma using enzyme-linked immunosorbent assay (ELISA). Positive correlation between the stimulation index of polyclonal activators (SIPA) for IL-18 production by the tumor and the relative content of poorly differentiated cells was revealed. The latter, in turn, was positively correlated with the numbers of normal and pathologic mitoses and the degree of malignancy. Cancer cells can produce IL-18, which is involved in the process of angiogenesis, stimulates invasion and metastasis. Decrease in SIPA for the production of IL-6 and GCSF by peripheral blood cells could serve as an indicator of malignant progression in invasive ductal breast carcinoma.

  8. Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells.

    Science.gov (United States)

    Zhang, Xueyan; Lou, Yuqing; Wang, Huimin; Zheng, Xiaoxuan; Dong, Qianggang; Sun, Jiayuan; Han, Baohui

    2015-04-01

    Wnt signaling plays an important role in regulating the activity of cancer stem cells (CSCs) in a variety of cancers. In this study, we explored the role of Wnt signaling in the lung cancer stem cells (LCSCs). LCSCs were obtained by sphere culture, for which human lung adenocarcinoma cell line SPC-A1 was treated with IGF, EGF and FGF-10. The stemness of LCSCs was confirmed by immunofluorescence, and pathway analysis was performed by functional genome screening and RT-PCR. The relationship between the identified signaling pathway and the expression of the stemness genes was explored by agonist/antagonist assay. Moreover, the effects of different signaling molecule inhibitors on sphere formation, cell viability and colony formation were also analyzed. The results showed that LCSCs were successfully generated as they expressed pluripotent stem cell markers Nanog and Oct 4, and lung distal epithelial markers CCSP and SP-C, by which the phenotype characterization of stem cells can be confirmed. The involvement of Wnt pathway in LCSCs was identified by functional genome screening and verified by RT-PCR. The expression of Wnt signaling components was closely related to the expression of the Nanog and Oct 4. Furthermore, targeting Wnt signaling pathway by using different signaling molecule inhibitors can exert anticancer effects. In conclusion, Wnt signaling pathway is involved in the stemness regulation of LCSCs and might be considered as a potential therapeutic target in lung adenocarcinoma.

  9. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  10. Could cancer and infection be adverse effects ofmesenchymal stromal cell therapy?

    Institute of Scientific and Technical Information of China (English)

    Martha L Arango-Rodriguez; Fernando Ezquer; Marcelo Ezquer; Paulette Conget

    2015-01-01

    Multipotent mesenchymal stromal cells [also referred toas mesenchymal stem cells (MSCs)] are a heterogeneoussubset of stromal cells. They can be isolated from bonemarrow and many other types of tissue. MSCs arecurrently being tested for therapeutic purposes (i.e.,improving hematopoietic stem cell engraftment, managinginflammatory diseases and regenerating damagedorgans). Their tropism for tumors and inflamed sites andtheir context-dependent potential for producing trophicand immunomodulatory factors raises the question asto whether MSCs promote cancer and/or infection. Thisarticle reviews the effect of MSCs on tumor establishment,growth and metastasis and also susceptibility to infectionand its progression. Data published to date shows aparadoxical effect regarding MSCs, which seems todepend on isolation and expansion, cells source anddose and the route and timing of administration. Cancerand infection may thus be adverse or therapeutic effectsarising form MSC administration.

  11. Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jameel Ahmad Khan

    Full Text Available BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in America. Monoclonal antibodies are a viable treatment option for inhibiting cancer growth. Tumor specific drug delivery could be achieved utilizing these monoclonal antibodies as targeting agents. This type of designer therapeutic is evolving and with the use of gold nanoparticles it is a promising approach to selectively deliver chemotherapeutics to malignant cells. Gold nanoparticles (GNPs are showing extreme promise in current medicinal research. GNPs have been shown to non-invasively kill tumor cells by hyperthermia using radiofrequency. They have also been implemented as early detection agents due to their unique X-ray contrast properties; success was revealed with clear delineation of blood capillaries in a preclinical model by CT (computer tomography. The fundamental parameters for intelligent design of nanoconjugates are on the forefront. The goal of this study is to define the necessary design parameters to successfully target pancreatic cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The nanoconjugates described in this study were characterized with various physico-chemical techniques. We demonstrate that the number of cetuximab molecules (targeting agent on a GNP, the hydrodynamic size of the nanoconjugates, available reactive surface area and the ability of the nanoconjugates to sequester EGFR (epidermal growth factor receptor, all play critical roles in effectively targeting tumor cells in vitro and in vivo in an orthotopic model of pancreatic cancer. CONCLUSION: Our results suggest the specific targeting of tumor cells depends on a number of crucial components 1 targeting agent to nanoparticle ratio 2 availability of reactive surface area on the nanoparticle 3 ability of the nanoconjugate to bind the target and 4 hydrodynamic diameter of the nanoconjugate. We believe this study will help define the design parameters for formulating better strategies

  12. Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Hui Yao

    2016-01-01

    Objective:To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer.Methods:A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected.Results:Progression-free survival and median overall survival (mOS) of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05); 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05), and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05).Conclusions:Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

  13. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells.

    Science.gov (United States)

    Eiró, Noemí; Sendon-Lago, Juan; Seoane, Samuel; Bermúdez, María A; Lamelas, Maria Luz; Garcia-Caballero, Tomás; Schneider, José; Perez-Fernandez, Roman; Vizoso, Francisco J

    2014-11-15

    Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy.

  14. STUDY ON EFFECTS OF ARSENIC TRIOXIDE ON GASTRIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    顾琴龙; 朱正纲; 洪鹤群; 刘炳亚; 尹浩然; 林言箴; 李宁丽

    2002-01-01

    Objective To evaluate the effects of arsenic trioxide (As2O3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As2O3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As2O3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As2O3 at a concentration of 0.5μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As2O3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As2O3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.

  15. Inhibitory effect of gold nanoparticles conjugated with interferon gamma and methionine on breast cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Nastaran Mohseni; Fatemeh Salehi Sarvestani; Mehdi Shafiee Ardestani; Fatemeh Kazemi-Lomedasht; Masoud Ghorbani

    2016-01-01

    Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Methods: Gold nanorods(10 nm) were conjugated with IFN-g and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.Results: Zetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-g. The median percentage of cell viability in 0.30 mg/m L concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 mg/m L concentration of gold nanoparticles complex was toxic on tumor cells(P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to77% in 0.30 mg/m L concentration of gold nanorods complex.Conclusions: The size and concentration of gold nanorods was not cytotoxic. However,their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells.

  16. Effect of Evodiamine on Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901 in Vitro

    Directory of Open Access Journals (Sweden)

    LIU Shao-ping

    2014-09-01

    Full Text Available Objective: To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods: After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT assay while apoptosis and cell-cycle phase distribution using flow cytometry. Results: In 0.01~30.00 μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16 μg/mL; the apoptosis rate was increased from 3.4% to 7.0%, 13.8% and 36.3% at concentrations of 0, 0.5, 1.5 and 30 μg/mL of evodiamine, respectively; the percentage of cells accumulated in G2/M phase was increased from 17.26% to 98.92% in the cells treated with evodiamine for 24 h in 0.01~30.00 μg/mL range of concentrations. Conclusion: Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.

  17. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON NATURAL KILLER CELLS IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    LI Yan; BAI De-jiao; WANG Kun; YANG Guo-liang; YUAN Hong-yin; SHAO Hua

    1999-01-01

    Objective: To study the effects of perioperative use of cimetidine on natural killer (NK) cells in gastrointestinal (GI) cancer patients. Methods: 49 GI cancer patients were randomized into treatment group which took cimetidine in the perioperative period, and control group which did not take the drug. NK cells were measured by immunocytochemical method, using mouse-anti-human CD57 monoclonal antibody as the primary antibody. Blood samples from 20 healthy volunteers were treated in the same way as normal control. Comparisons were made within and between groups. Results: The NK cell percentage of normal control was 18.50±2.31. Both groups of patients had significantly lower than normal NK percentages before treatment (P<0.05). NK cell percentages at admission,before operation, on the 2nd and the 10th postoperative days were 14.60±3.91, 15.64±3.61, 17.40±3.28, 20.68±4.13, respectively, for the treatment group, and 14.88±2.76, 13.17±2.93, 14.50±2.77, 15.67±2.55, respectively,for control group. The difference between the two groups was statistically significant. Conclusion: Perioperative cimetidine application can help restore NK cells. The drug may be useful to reverse postoperative immuno-depression in GI cancer patients.

  18. The effect of bovine milk lactoferrin on human breast cancer cell lines.

    Science.gov (United States)

    Duarte, D C; Nicolau, A; Teixeira, J A; Rodrigues, L R

    2011-01-01

    The evidence that biologically active food components are key environmental factors affecting the incidence of many chronic diseases is overwhelming. However, the full extent of such components in our diet is unknown, as is our understanding of their mechanisms of action. Beyond the interaction of these food components with the gut and intestinal immune functions, whey proteins such as lactoferrin are being tested as anticancer agents. Lactoferrin is an iron-binding protein that has been reported to inhibit several types of cancer. In the present work, the effects of bovine milk lactoferrin on human breast cancer HS578T and T47D cells were studied. The cells were either untreated or treated with lactoferrin concentrations ranging from 0.125 to 125 μM. Lactoferrin decreased the cell viability of HS578T and T47D by 47 and 54%, respectively, and increased apoptosis about 2-fold for both cell lines. Proliferation rates decreased by 40.3 and 63.9% for HS578T and T47D, respectively. For the T47D line, cell migration decreased in the presence of the protein. Although the mechanisms of action are not fully known, the results gathered in this work suggest that lactoferrin interferes with some of the most important steps involved in cancer development.

  19. Inhibitory effect of lanthanum chloride on migration and invasion of cervical cancer cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Hongwei; LIU Sisun; MIAO Lifang; YU Lingfang; WANG Yang; GUO Fei

    2013-01-01

    Tumor metastasis remains the main reason for treatment failure and death of patients with cervical cancer.The present study was designed to explore the effects of lanthanum chloride (LaCl3) on the invasion and migration of cervical cancer cells and the underlying mechanisms.The migration and invasion of tumor cells was evaluated by a modified Transwell/Boyden chamber assays.It is well known that MMPs (Matrix metalloprotcinascs) and NF-κB (Nuclear factor-κB) pathway play important roles in migration and invasion of tumor cells,and also the expression of MMPs were regulated by NF-κB signaling.The expression of MMP-1 and MMP-9 was detected by reverse transcription polymerase chain reaction (RT-PCR); Western blot and the NF-κB-DNA-binding activity assay were used to analyze the NF-κB activity.The results indicated that LaCl3 was capable of inhibiting the cell invasion and migration of human cervical cancer Hela cells by decreasing the expression of MMP-1 and MMP-9 via blocking NF-κB pathway.

  20. In-vitro cancer cell cytotoxicity and alpha amylase inhibition effect of seven tropical fruit residues

    Institute of Scientific and Technical Information of China (English)

    Priti Gupta; Ira Bhatnagar; Se-Kwon Kim; Ajay Kumar Verma; Anubhuti Sharma

    2014-01-01

    Objective:To determine quantitative phytochemical, anticancer and antidiabetic effect of seven Indian tropical fruit residues. Methods:In-vitro cytotoxic activity (IC50) was evaluated against cervical cancer cells (HeLa), breast cancer cells (MCF-7), hepatocellular carcinoma cells (HepG-2) and bone sarcoma cells (MG-63) and alpha amylase inhibition assay was used for antidiabetic activity. Results: Results of phytochemical analysis revealed that all residues contained remarkable amount of alkaloid, saponin, tannin and flavonoid. Notable cancer cell growth inhibition was observed for the extract from Carissa carandas pomace and Litchi sinensis seeds with IC50 values ranged from 56.72 to 89.24 μg/mL. Alpha amylase inhibition assay was measured at six different concentrations (5, 10, 25, 50, 100 and 200 mg/mL) by using different solvent extract. Results showed that Carissa carandas possessed best activity with IC50 value as 29.66 mg/mL followed by other residues in methanol extract. Conclusions:Study suggests that these fruit residues demonstrate promising antidiabetic and anticancer activity that substantiated its ethno medicinal use and may provide new molecules for the treatment of these diseases.

  1. Inhibitory effect of Trolox on the migration and invasion of human lung and cervical cancer cells.

    Science.gov (United States)

    Sung, Ho Joong; Kim, Yoonseo; Kang, Hyereen; Sull, Jae Woong; Kim, Yoon Suk; Jang, Sung-Wuk; Ko, Jesang

    2012-02-01

    The antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) is implicated in migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of Trolox on metastatic cancer cells is not known. We found that a non-cytotoxic dose of Trolox decreased phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration of both A549 and HeLa cancer cells. We also found that Trolox suppressed both the expression and the proteolytic activity of matrix metalloproteinase-9 (MMP-9), and that the promoter activity of PMA-induced MMP-9 was inhibited by Trolox. Our results show that Trolox inhibits the transcriptional activity of MMP-9 by suppression of NF-κB transactivation. These results indicate that Trolox inhibits NF-κB-mediated MMP-9 expression, leading to the suppression of migration and invasion in lung and cervical cancer cells. Trolox is a potential agent for clinical use in preventing the invasion and metastasis of human malignant lung and cervical cancers.

  2. Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hong Sun; Juan Ren; Qing Zhu; Fan-Zhong Kong; Lei Wu; Bo-Rong Pan

    2009-01-01

    AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosisin the human colon cancer cell line, SW480, and its mechanisms of action. METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor,PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner (P < 0.05). Rho kinase inhibitor,Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05),but the phosphoinositide 3-kinase (PI3K) inhibitor,LY294002, significantly blocked the protective effect of LPA on apoptosis.CONCLUSION: LPA stimulated proliferation, adhesion,migration of SW480 cells, and protected from apoptosis.The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3KAKT/ PKB signal pathways may be involved.

  3. Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells

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    Yuan Sun, Ying-xia Li, Hai-jun Wu, Si-hung Wu, Y. Alan Wang, Dian-zhong Luo, D. Joshua Liao

    2011-01-01

    Full Text Available Introduction: Cyclin D1 (D1 binds to cyclin-dependent kinases (CDK 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H-dione (NPCD, a novel CDK4 inhibitor, on breast cancer cell lines.Methods: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation.Results: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines.Conclusions: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of

  4. Power-Law Modeling of Cancer Cell Fates Driven by Signaling Data to Reveal Drug Effects

    Science.gov (United States)

    Zhang, Fan; Wu, Min; Kwoh, Chee Keong; Zheng, Jie

    2016-01-01

    Extracellular signals are captured and transmitted by signaling proteins inside a cell. An important type of cellular responses to the signals is the cell fate decision, e.g., apoptosis. However, the underlying mechanisms of cell fate regulation are still unclear, thus comprehensive and detailed kinetic models are not yet available. Alternatively, data-driven models are promising to bridge signaling data with the phenotypic measurements of cell fates. The traditional linear model for data-driven modeling of signaling pathways has its limitations because it assumes that the a cell fate is proportional to the activities of signaling proteins, which is unlikely in the complex biological systems. Therefore, we propose a power-law model to relate the activities of all the measured signaling proteins to the probabilities of cell fates. In our experiments, we compared our nonlinear power-law model with the linear model on three cancer datasets with phosphoproteomics and cell fate measurements, which demonstrated that the nonlinear model has superior performance on cell fates prediction. By in silico simulation of virtual protein knock-down, the proposed model is able to reveal drug effects which can complement traditional approaches such as binding affinity analysis. Moreover, our model is able to capture cell line specific information to distinguish one cell line from another in cell fate prediction. Our results show that the power-law data-driven model is able to perform better in cell fate prediction and provide more insights into the signaling pathways for cancer cell fates than the linear model. PMID:27764199

  5. Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yamila B. Gándola

    2014-01-01

    Full Text Available Lecithins, mainly composed of the phospholipids phosphatidylcholines (PC, have many different uses in the pharmaceutical and clinical field. PC are involved in structural and biological functions as membrane trafficking processes and cellular signaling. Considering the increasing applications of lecithin-based nanosystems for the delivery of therapeutic agents, the aim of the present work was to determine the effects of phosphatidylcholine nanoparticles over breast cancer cellular proliferation and signaling. PC dispersions at 0.01 and 0.1% (w/v prepared in buffer pH 7.0 and 5.0 were studied in the MCF-7 breast cancer cell line. Neutral 0.1% PC-derived nanoparticles induced the activation of the MEK-ERK1/2 pathway, increased cell viability and induced a 1.2 fold raise in proliferation. These biological effects correlated with the increase of epidermal growth factor receptor (EGFR content and its altered cellular localization. Results suggest that nanoparticles derived from PC dispersion prepared in buffer pH 7.0 may induce physicochemical changes in the plasma membrane of cancer cells which may affect EGFR cellular localization and/or activity, increasing activation of the MEK-ERK1/2 pathway and inducing proliferation. Results from the present study suggest that possible biological effects of delivery systems based on lecithin nanoparticles should be taken into account in pharmaceutical formulation design.

  6. Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

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    Assunta Raiola

    2015-12-01

    Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

  7. Inhibitory Effect of Isoflavones on Prostate Cancer Cells and PTEN Gene

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daidzein and cell viability was determined by MTT assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells.Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (Erα), estrogen receptor beta gene (Erβ), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF). Results The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC-3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein. Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, Erα and Erβ genes decreased and AR gene was not expressed after incubation with genistein and daidzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of Erα and Erβ gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a time- and dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 cells directly. The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Akt pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key

  8. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

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    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  9. Inhibiting effect of antisense hTRT on telomerase activity of human liver cancer cell line SMMC-7721

    Institute of Scientific and Technical Information of China (English)

    牟娇; 李晓冬; 杨庆; 贾凤岐; 卫立辛; 郭亚军; 吴孟超

    2003-01-01

    Objective: To induce changes in biological character of human liver cancer cell line SMMC-7721 by blocking the expression of telomerase genes hTRT and to explore its value in cancer gene therapy. Methods: The vehicle for eukaryotic expression of antisense hTRT was constructed and then transfected into SMMC-7721 cells. The effects of antisense hTRT gene on telomerase activity, cancer cell growth and malignant phenotypes were analyzed. Results: The obtained transfectants that could express antisense hTRT gene stably showed marked decrease in telomerase activity; the shortening of telomere was obvious; cells presented contact growth inhibition; in nude mice transplantation, the rate of tumor induction dramatically decreased. Conclusion: Antisense hTRT gene expression can significantly inhibit telomerase activity of cancer cells and decrease malignant phenotypes in vitro and in vivo. Therefore, as a telomerase inhibitor, antisense hTRT gene may be a new pathway for cancer therapy.

  10. Estrogenic effects of fusarielins in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Søndergaard, Teis; Klitgaard, Louise Graabæk; Purup, Stig

    2012-01-01

    The fusarielins are a group of metabolites found in several Aspergillus and Fusarium species that have been reported to have with weak antifungal, antibiotic and cytotoxic effects. This study identifies fusarielin A, F, G and H isolated from Fusarium as mycoestrogens. Mycoestrogens are compounds ...

  11. Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration.

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    Su-Hyeong Kim

    Full Text Available Phenethyl isothiocyanate (PEITC is a promising cancer chemopreventive component of edible cruciferous vegetables with in vivo efficacy against prostate cancer in experimental rodents. Cancer chemopreventive response to PEITC is characterized by its ability to inhibit multiple oncogenic signaling pathways, including nuclear factor-κB, Akt, and androgen receptor. The present study demonstrates, for the first time, that PEITC treatment activates Notch signaling in malignant as well as normal human prostate cells. Exposure of human prostate cancer cells (LNCaP, PC-3, and DU145 and a normal human prostate epithelial cell line (PrEC to PEITC resulted in cleavage (active form of Notch1 and Notch2, and increased transcriptional activity of Notch. In PC-3 and LNCaP cells, PEITC treatment caused induction of Notch ligands Jagged1 and Jagged2 (PC-3, overexpression of γ-secretase complex components Presenilin1 and Nicastrin (PC-3, nuclear enrichment of cleaved Notch2, and/or up-regulation of Notch1, Notch2, Jagged1, and/or Jagged2 mRNA. PEITC-induced apoptosis in LNCaP and PC-3 cells was significantly attenuated by RNA interference of Notch2, but not by pharmacological inhibition of Notch1. Inhibition of PC-3 and LNCaP cell migration resulting from PEITC exposure was significantly augmented by knockdown of Notch2 protein as well as pharmacological inhibition of Notch1 activation. Nuclear expression of cleaved Notch2 protein was significantly higher in PC-3 xenografts from PEITC-treated mice and dorsolateral prostates from PEITC-fed TRAMP mice compared with respective control. Because Notch signaling is implicated in epithelial-mesenchymal transition and metastasis, the present study suggests that anti-metastatic effect of PEITC may be augmented by a combination regimen involving a Notch inhibitor.

  12. Determining the effect of DNA methylation on gene expression in cancer cells.

    Science.gov (United States)

    Lee, Chai-Jin; Evans, Jared; Kim, Kwangsoo; Chae, Heejoon; Kim, Sun

    2014-01-01

    DNA methylation, a DNA modification by adding methyl group to cytosine, has an important role in the regulation of gene expression. DNA methylation is known to be associated with gene transcription by interfering with DNA-binding proteins, such as transcription factors. DNA methylation is closely related to tumorigenesis, and the methylation state of some genes can be used as a biomarker for tumorigenesis. Aberrant DNA methylation of genomic regions, including CpG islands, CpG shores, and first exons, is related to the altered gene expression pattern characteristics of all human cancers. Subheading 1 surveys recent developments on DNA methylation and gene expressions in cancer. Then we provide analysis of DNA methylation and gene expression in 30 breast cancer cell lines representing different tumor phenotypes. This study conducted an integrated analysis to identify the relationship between DNA methylation in various genomic regions and expression levels of downstream genes, using MethylCapseq data (affinity purification followed by next-generation sequencing of eluted DNA) and Affymetrix gene expression microarray data. The goal of this study was to assess genome-wide methylation profiles associated with different molecular subtypes of human breast cancer (luminal, basal A, and basal B) and to comprehensively investigate the effect of DNA methylation on gene expression in breast cancer phenotypes. This showed that methylation of genomic regions near transcription start sites, CpG island, CpG shore, and first exon was strongly associated with gene repression, and the effects of the regions on gene expression patterns were different for different molecular subtypes of breast cancer. The results further indicated that aberrant methylation of specific genomic regions was significantly associated with different breast cancer subtypes.

  13. Effects of astragali radix on the growth of different cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Jiang Lin; Hui-Fang Dong; JJ Oppenheim; OM Howard

    2003-01-01

    AIM: To investigate the inhibitory effect of a Chinese herb medicine Astragali radix (AR) on growth of different cancer cell lines.METHODS: To observe the in vitro effects of AR on tumor cell proliferation by trypan blue exclusion, MTS method and tritium thymidine incorporation assay. Apoptosis was detected by DNA ladder method.RESULTS: The inhibition rates of AR on the cell respiration of AGS, KATOⅢ, HT29, MDA231, MEL7 and MEL14 were 68.25%, 62.36%, 22.8%, 27.69%, 2.85% and 5.14%respectively at the concentration of 100 ug/ml; it inhibited AGS DNA synthesis by 87.33% at the concentration of 50ug/ml. The inhibitory effect on AGS was time-and dosedependent. AR did not induce apoptosis in AGS cells.CONCLUSION: AR specifically inhibits gastric cancer cells growth in vitro and the mechanism is mainly cytostatic but not cytotoxic or inducing apoptosis.

  14. Maturation of dendritic cells by pullulan promotes anti-cancer effect

    Science.gov (United States)

    Xu, Li; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-01-01

    Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines. PMID:27341129

  15. Effect of diglycine mutant FAT10 on the proliferation and apoptosis of cervical cancer cells

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    Cui LI

    2015-01-01

    Full Text Available Objective To investigate the effects of FAT10ΔGG, a carboxyl-terminal diglycine deficient mutant, on the proliferation and apoptosis of cervical cancer cell line HeLa. Methods Specimens of cervical carcinoma in situ and normal cervix tissue, 5 each, were collected. The expressive levels of FAT10 protein in these specimens were detected by Western blotting. Sitedirected mutagenesis was applied to construct the mutant pcDNA3.0-flag-FAT10ΔGG plasmid. The HeLa cells were then transiently transfected with wild-type FAT10, FAT10ΔGG and empty vector (used as negative control, and the wild-type HeLa cells served as blank control. The transfection efficiency of FAT10 or FAT10ΔGG was detected by Western blotting, and cell proliferation was determined by CCK-8 assay. Cisplatin was used to induce cell apoptosis after cells were transfected for 24h, and the cell apoptotic rates of all groups were determined by flow cytometry. Results Western blotting showed a significantly increased expression of FAT10 protein in cervical carcinoma tissues compared with that in normal cervical tissue. Over-expression of wild FAT10 in HeLa cells obviously promoted cell proliferation, but this promotion was significantly inhibited in cells transfected with its diglycine mutant. Compared with blank control group (22.7%±4.2% and negative control group (24.1%±3.8%, the apoptotic rate was significantly reduced in wild FAT10 group (10.9%±2.0%, P0.05. Conclusion FAT10 can promote cell proliferation and inhibit cell apoptosis through its carboxyl-terminal diglycine motif, and it may play an essential role in carcinogenesis and development of cancer. DOI: 10.11855/j.issn.0577-7402.2014.12.01

  16. The effect of moderately halophilic bacteria supernatant on proliferation and apoptosis of cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Sarvari, S; Seyedjafari, E; Amoozgar, M A; Bakhshandeh, B

    2015-06-10

    Many drug discoveries and developing of their applications has originated from microbial metabolites. The most efforts in development of new drugs are concerned with anti—cancer agents that cause better treatment results, less side effects, and more economical production. Several anti—tumor drugs have been recently extracted from natural microbial products. Among these various microbial diversity, Marin bacteria and Archaea have been considered as important and efficient organisms to serve as manufacturers of diverse bioactive compounds. Moderately halophilic microorganisms isolated from saline ponds and lakes of Iran show high capability for production of bioactive compounds like enzymes, dyes and anti—cancer agents. In this research, nine moderately halophilic bacteria isolates were screened to evaluate their anti—cancer agent productivity. After five days of culture on suitable mediums, supernatant samples were tested for in vitro anti—proliferative activity against Human Umbilical Vein Endothelial Cells (HUVEC) while same concentrations of supernatants were examined for evaluating of proliferative activity against Adipose—derived Mesenchymal stem cells (MSCs). Both assessments were carried out by MTT assay and double PI and DAPI staining. GASX17, GBWy6 and GBPX3 isolates just induced HUVEC cell deaths and exhibited anti—proliferative activity while R2S12 not only reduced HUVEC cell proliferation but also enhanced proliferation of MSCs. R2S12 , GASX17, GBWy6 and GBPX3 isolates were characterized biochemically and six hydrophilic components were detected. This research established new bioactive compounds that could be used as an effective treatment in chemotherapy.

  17. Molecular mechanism underlying the antiproliferative effect of suppressor of cytokine signaling-1 in non-small-cell lung cancer cells.

    Science.gov (United States)

    Shimada, Kazuki; Serada, Satoshi; Fujimoto, Minoru; Nomura, Shintaro; Nakatsuka, Rie; Harada, Emi; Iwahori, Kota; Tachibana, Isao; Takahashi, Tsuyoshi; Kumanogoh, Atsushi; Kishimoto, Tadamitsu; Naka, Tetsuji

    2013-11-01

    Lung cancer (LC) is the major cause of death by cancer and the number of LC patients is increasing worldwide. This study investigated the therapeutic potential of gene delivery using suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of intracellular signaling pathways, for the treatment of LC. To examine the antitumor effect of SOCS-1 overexpression on non-small-cell lung cancer (NSCLC) cells, NSCLC cells (A549, LU65, and PC9) were infected with adenovirus-expressing SOCS-1 vector. The cell proliferation assay showed that A549 and LU65, but not PC9, were sensitive to SOCS-1 gene-mediated suppression of cell growth. Although JAK inhibitor I could also inhibit proliferation of A549 and LU65 cells, SOCS-1 gene delivery appeared to be more potent as SOCS-1 could suppress focal adhesion kinase and epidermal growth factor receptor, as well as the JAK/STAT3 signaling pathway. Enhanced phosphorylation of the p53 protein was detected by means of phospho-kinase array in SOCS-1 overexpressed A549 cells compared with control cells, whereas no phosphorylation of p53 was observed when JAK inhibitor I was used. Furthermore, treatment with adenoviral vector AdSOCS-1 in vivo significantly suppressed NSCLC proliferation in a xenograft model. These results suggest that the overexpression of SOCS-1 gene is effective for antitumor therapy by suppressing the JAK/STAT, focal adhesion kinase, and epidermal growth factor receptor signaling pathways and enhancing p53-mediated antitumor activity in NSCLC.

  18. The dual effects of polar methanolic extract of Hypericum perforatum L. in bladder cancer cells

    Science.gov (United States)

    Nseyo, U. O.; Nseyo, O. U.; Shiverick, K. T.; Medrano, T.; Mejia, M.; Stavropoulos, N.; Tsimaris, I.; Skalkos, D.

    2007-02-01

    Introduction and background: We have reported on the polar methanolic fraction (PMF) of Hypericum Perforatum L as a novel photosensitizing agent for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). PMF has been tested in human leukemic cells, HL-60 cells, cord blood hemopoietic progenitor cells, bladder cancers derived from metastatic lymph node (T-24) and primary papillary bladder lesion (RT-4). However, the mechanisms of the effects of PMF on these human cell lines have not been elucidated. We have investigated mechanisms of PMF + light versus PMF-alone (dark experiment) in T-24 human bladder cancer cells. Methods: PMF was prepared from an aerial herb of HPL which was brewed in methanol and extracted with ether and methanol. Stock solutions of PMF were made in DSMO and stored in dark conditions. PMF contains 0.57% hypericin and 2.52% hyperforin. The T24 cell line was obtained from American Type Culture Collection (ATCC). In PDT treatment, PMF (60μg/ml) was incubated with cells, which were excited with laser light (630nm) 24 hours later. Apoptosis was determined by DNA fragmentation/laddering assay. DNA isolation was performed according to the manufacture's instructions with the Kit (Oncogene Kit#AM41). Isolated DNA samples were separated by electrophoresis in 1.5% in agarose gels and bands were visualized by ethidium bromide labeling. The initial cell cycle analysis and phase distribution was by flow cytometry. DNA synthesis was measured by [3H] thymidine incorporation, and cell cycle regulatory proteins were assayed by Western immunoblot. Results: The results of the flow cytometry showed PMF +light induced significant (40%) apoptosis in T24 cells, whereas Light or PMF alone produced little apoptosis. The percentage of cells in G 0/G I phase was decreased by 25% and in G2/M phase by 38%. The main impact was observed on the S phase which was blocked by 78% from the specific photocytotoxic process. DNA laddering analysis showed that PMF (60

  19. Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells.

    Directory of Open Access Journals (Sweden)

    Yimiao Xu

    Full Text Available BACKGROUND: It was well known that the clinical use of chemotherapeutic drugs is restricted by severe adverse reactions and drug resistances. Thus it is necessary to figure out a strategy to increase the specific anti-tumor efficiency of chemotherapeutic drugs. Apigenin, a kind of flavonoids, has been reported to possess anticancer activities with very low cytotoxicity to normal tissue. METHODOLOGY/PRINCIPAL FINDINGS: Our results from cell viability assay, western-blots and TdT-mediated dUTP-biotin nick end labeling (TUNEL assay demonstrated the synergistic pro-apoptotic effects of a low dose of apigenin and paclitaxel in human cancer cell lines. To analyze the underlying mechanism, we examined reactive oxygen species (ROS staining after cells were treated with a combination of apigenin and paclitaxel, or each of them alone. Data from flow-cytometry showed that superoxides but not reduction of peroxides accumulated in HeLa cells treated with apigenin or a combination of apigenin and paclitaxel. Apigenin and paclitaxel-induced HeLa cell apoptosis was related to the level of ROS in cells. We further evaluated activity and protein level of superoxide dismutase (SOD. Apigenin significantly inhibited SOD activity but did not alter the SOD protein level suggesting that apigenin promoted ROS accumulation through suppressing enzyme activity of SOD. Addition of Zn(2+, Cu(2+ and Mn(2+ to cell lysates inhibited apigenin's effects on SOD activity. At the same time, data from caspase-2 over-expression and knocked-down experiments demonstrated that caspase-2 participated in apigenin and paclitaxel-induced HeLa cell apoptosis. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated that apigenin can sensitize cancer cells to paclitaxel induced apoptosis through suppressing SOD activity, which then led to accumulation of ROS and cleavage of caspase-2, suggesting that the combined use of apigenin and paclitaxel was an effective way to decrease the dose

  20. Effects of airborne particulate matter on alternative pre-mRNA splicing in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Buggiano, Valeria; Petrillo, Ezequiel; Alló, Mariano; Lafaille, Celina [Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires (Argentina); Redal, María Ana [Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires (Argentina); Alghamdi, Mansour A. [Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah (Saudi Arabia); Khoder, Mamdouh I. [Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah (Saudi Arabia); Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah (Saudi Arabia); Shamy, Magdy [Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah (Saudi Arabia); Muñoz, Manuel J., E-mail: mmunoz@fbmc.fcen.uba.ar [Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires (Argentina); and others

    2015-07-15

    Alternative pre-mRNA splicing plays key roles in determining tissue- and species-specific cell differentiation as well as in the onset of hereditary disease and cancer, being controlled by multiple post- and co-transcriptional regulatory mechanisms. We report here that airborne particulate matter, resulting from industrial pollution, inhibits expression and specifically affects alternative splicing at the 5′ untranslated region of the mRNA encoding the bone morphogenetic protein BMP4 in human colon cells in culture. These effects are consistent with a previously reported role for BMP4 in preventing colon cancer development, suggesting that ingestion of particulate matter could contribute to the onset of colon cell proliferation. We also show that the underlying mechanism might involve changes in transcriptional elongation. This is the first study to demonstrate that particulate matter causes non-pleiotropic changes in alternative splicing. - Highlights: • Airborne particulate matter (PM10) affects alternative splicing in colon cells. • PM10 upregulates one of the two mRNA variants of the growth factor BMP-4. • This variant has a longer 5′ unstranslated region and introduces an upstream AUG. • By regulating BMP-4 mRNA splicing PM10 inhibits total expression of BMP-4 protein. • BMP-4 downregulation was previously reported to be associated to colon cancer.

  1. Inhibitory effects of ginseng sapogenins on the proliferation of triple negative breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Kwak, Jin Ho; Park, Jun Yeon; Lee, Dahae; Kwak, Jae Young; Park, Eun Hwa; Kim, Ki Hyun; Park, Hye-Jin; Kim, Hyun Young; Jang, Hyuk Jai; Ham, Jungyeob; Hwang, Gwi Seo; Yamabe, Noriko; Kang, Ki Sung

    2014-12-01

    Because of poor prognosis, clinical treatment of triple-negative (TN) breast cancer remains the most challenging factor in cancer treatment. Extensive research into alternative cancer therapies includes studying the naturopathic effects of the medicinal herb ginseng. This study investigates the anti-neoplastic properties of ginseng sapogenins and the derivatives: (1) (20(S)-protopanaxadiol (PPD), (2) 20(S)-protopanaxatriol), (3) (20(S)-dihydroprotopanaxadiol, and (4) 20(S)-dihydroprotopanaxatriol). These compounds were found to prevent the proliferation of MDA-MB-231 human breast cancer cells. PPD was the most potent inhibitor, exhibiting an IC₅₀ (5.87 μM) comparable to that of the chemotherapeutic drug taxol. Furthermore, PPD induced dose-dependent cleavage of caspase-8, caspase-3, and PARP in MDA-MB-231 cells. Thus, we propose that PPD acts as anti-cancer agent by stimulating caspase-dependent apoptosis in breast cancer cells.

  2. Anticancer Effect of Ferulago Mughlea Peşmen (Apiaceae) on Cancer Cell Proliferation

    Science.gov (United States)

    Filiz, Bakar; Songül, Karakay; Bostanlık, Delimustafaoğlu; Gül, Fatma; Ceyda Sibel, Kılıç

    2016-01-01

    Ferulago W. Koch. (Apiaceae) genus is represented by approximately 50 taxa throughout the world. Ferulago species are known as “Çakşır” or “Çağşır” in Turkey and mostly known for their aphrodisiac effects. However recent reports emphasize the activity of various Ferulago species against cancer, as well. The aim of this study was to investigate the effect of lyophilized extract of F. mughlea Peşmen, a species endemic for Turkey, on cancer cell proliferation. For this purpose human prostate (PC-3) and colorectal (SW-480) carcinoma cells were used to evaluate the antiproliferative effects of Ferulago W. Koch and the measurements were performed via MTT test. Lyophilized extracts obtained from aerial parts and the roots exhibited potent inhibitor effects on cell proliferation. Aerial part of the plant inhibited the proliferation of SW-480 cell at 48th hour with a 0.119 mg/mL IC50 value. PMID:27980585

  3. Singlet oxygen mediated DNA degradation by copper nanoparticles: potential towards cytotoxic effect on cancer cells

    Directory of Open Access Journals (Sweden)

    Sengupta Tapas K

    2011-03-01

    Full Text Available Abstract The DNA degradation potential and anti-cancer activities of copper nanoparticles of 4-5 nm size are reported. A dose dependent degradation of isolated DNA molecules by copper nanoparticles through generation of singlet oxygen was observed. Singlet oxygen scavengers such as sodium azide and Tris [hydroxyl methyl] amino methane were able to prevent the DNA degradation action of copper nanoparticles confirming the involvement of activated oxygen species in the degradation process. Additionally, it was observed that the copper nanoparticles are able to exert cytotoxic effect towards U937 and Hela cells of human histiocytic lymphoma and human cervical cancer origins, respectively by inducing apoptosis. The growth characteristics of U937 and Hela cells were studied applying various concentrations of the copper nanoparticles.

  4. Effect of miR-296 on the Apoptosis of Androgen-independent Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Pei CHENG; Run-sheng LI; Biao-yang LIN; Wei-qun WANG; Yu-hua LI; Yan GUO; Wei LI

    2009-01-01

    Objective To investigate the miR-296's function in prostate carcinoma(PCa) cells. Methods In order to profile the miRNA expression in LNCaP cells, the cultured cells were stimulated with androgen after 48-h starvation, miRNA microarray analysis and Q-RT-PCR assay were performed. To characterize the effects of miR296 on PCa cells, CL-1 and PC-3 cells were transfected with miR-296 and antisense-miR-296, cell growth and apoptosis were then analyzed. Results The miR-296-5p expression was up-regulated by 2.22 folds in the CL-1 cells, which do not express significantly androgen receptor, than in LNCaP cells. Knockdown of miR-296-Sp induced apoptosis of CL-1 cells, but not LNCaP cells. However, knockdown of miR-296-Sp inhibited the growth rate of LNCaP cells cultured in absence of androgen. Conclusion MiR-296-5p could be irnportant for development of prostate cancer from androgen dependence to androgen independence.

  5. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    Science.gov (United States)

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    Cancer cells undergo an increased steady-state ROS condition compared to normal cells. Among the major metabolic differences between cancer cells and normal cells is the dependence of cancer cells on glycolysis as a major source of energy even in the presence of oxygen (Warburg effect). In Warburg effect, glucose is catabolized to lactate that is extruded through monocarboxylate transporters to the microenvironment of cancer cells, while in normal cells, glucose is metabolized into pyruvate that is not extruded. Pyruvate is a potent antioxidant, while lactate has no antioxidant effect. Pyruvate in normal cells may be further metabolized to acetyl CoA and then through Krebs cycle with production of antioxidant intermediates e.g. citrate, malate and oxaloacetate together with the reducing equivalents (NADH.H+). Through activity of mitochondrial transhydrogenase, NADH.H+ replenishes NADPH.H+, coenzyme of glutathione reductase which replenishes reduced form of glutathione (potent antioxidant). This enhances antioxidant capacities of normal cells, while cancer cells exhibiting Warburg effect may be deprived of all that antioxidant capabilities due to loss of extruded lactate (substrate for Krebs cycle). Although intrinsic oxidative stress in cancer cells is high, it may be prevented from reaching progressively increasing levels that are cytotoxic to cancer cells. This may be due to some antioxidant effects exerted by hexokinase II (HK II) and NADPH.H+ produced through HMP shunt. Glycolytic phenotype in cancer cells maintains a high non-toxic oxidative stress in cancer cells and may be responsible for their malignant behavior. Through HK II, glycolysis fuels the energetic arm of malignancy, the mitotic arm of malignancy (DNA synthesis through HMP shunt pathway) and the metastatic arm of malignancy (hyaluronan synthesis through uronic acid pathway) in addition to the role of phosphohexose isomerase (autocrine motility factor). All those critical three arms start with the

  6. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Johannes Klose

    Full Text Available Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0-10 µM, comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.

  7. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.

    Science.gov (United States)

    Klose, Johannes; Stankov, Metodi V; Kleine, Moritz; Ramackers, Wolf; Panayotova-Dimitrova, Diana; Jäger, Mark D; Klempnauer, Jürgen; Winkler, Michael; Bektas, Hüseyin; Behrens, Georg M N; Vondran, Florian W R

    2014-01-01

    Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC) cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH) likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0-10 µM), comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS) formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.

  8. Chemically unassisted phototherapy: dose effects via real-time optical monitoring of cancer cells

    Science.gov (United States)

    Landry, Sylvie; Keeler, Werden

    2010-03-01

    Ultraviolet (UV) light and short wavelength visible (VIS) light have been used to kill pathogens for many years. Although the adverse effects of UV radiation on living cells have been extensively studied using biochemical and biomolecular techniques, most of the light therapies used for medical treatment are chemically assisted (i.e., photodynamic therapy). However, the use of light alone could prove both cost and therapeutically effective as an alternative treatment modality for localized diseases. In this study, real-time oblique incidence reflection (OIR) microscopy and image analysis were used to visualize and quantify the effects of chemically unassisted light therapy on untagged live cancer cells in vitro. The incident radiation fluence (in mJ/cm^2) required to induce cell death was determined for selected quasi-monochromatic UV to VIS wavelengths ranging from 275nm to 460nm. A predictive mathematical equation quantifying the lethal fluence as a function of wavelength will be discussed.

  9. Regulation of the Warburg Effect in Early-Passage Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ian F. Robey

    2008-08-01

    Full Text Available Malignancy in cancer is associated with aerobic glycolysis (Warburg effect evidenced by increased trapping of [18F]deoxyglucose (FdG in patients imaged by positron emission tomography (PET. [18F]deoxyglucose uptake correlates with glucose transporter (GLUT-1 expression, which can be regulated by hypoxia-inducible factor 1 alpha (HIF-1α. We have previously reported in established breast lines that HIF-1α levels in the presence of oxygen leads to the Warburg effect. However, glycolysis and GLUT-1 can also be induced independent of HIF-1α by other factors, such as c-Myc and phosphorylated Akt (pAkt. This study investigates HIF-1α, c-Myc, pAkt, and aerobic glycolysis in low-passage breast cancer cells under the assumption that these represent the in vivo condition better than established lines. Similar to in vivo FdG-PET or primary breast cancers, rates of glycolysis were diverse, being higher in cells expressing both c-Myc and HIF-1α and lower in cell lines low or negative in both transcription factors. No correlations were observed between glycolytic rates and pAkt levels. Two of 12 cell lines formed xenografts in mice. Both were positive for HIF-1α and phosphorylated c-Myc, and only one was positive for pAkt. Glycolysis was affected by pharmacological regulation of c-Myc and HIF-1α. These findings suggest that c-Myc and/or HIF-1α activities are both involved in the regulation of glycolysis in breast cancers.

  10. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status.

    Science.gov (United States)

    DE Oliveira, Daiane Teixeira; Savio, Andre Luiz Ventura; Marcondes, Joao Paulo DE Castro; Barros, Tatiane Martins; Barbosa, Ludmila Correia; Salvadori, Daisy Maria Favero; DA Silva, Glenda Nicioli

    2017-03-01

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.

  11. The Antiproliferative Effect of Moringa oleifera Crude Aqueous Leaf Extract on Human Esophageal Cancer Cells.

    Science.gov (United States)

    Tiloke, Charlette; Phulukdaree, Alisa; Chuturgoon, Anil A

    2016-04-01

    Esophageal cancer (EC) is commonly diagnosed in South Africa (SA), with high incidences occurring in SA's black population. Moringa oleifera (MO), a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of ailments, including cancer. We investigated the antiproliferative effect of MO crude aqueous leaf extract (MOE) on a cancerous esophageal cell line (SNO). SNO cells were exposed to a range of MOE dilutions to evaluate cytotoxicity (MTT assay). Oxidative stress was determined using the TBARS assay. The comet assay was used to assess DNA damage. We then determined cell death mechanisms by measuring phosphatidylserine (PS) externalization (flow cytometry), caspase-3/7 and caspase-9 activities, and adenosine triphosphate (ATP) levels (luminometry). Protein expression of Smac/DIABLO and PARP-1 was determined by western blotting. SNO cells were treated with a range of MOE dilutions to obtain an IC50 value of 389.2 μg/mL MOE (24 h), which was used in all subsequent assays. MOE significantly increased lipid peroxidation (P < .05) and DNA fragmentation (P < .0001) in SNO cells. The induction of apoptosis was confirmed by the increase in PS externalization (P < .0001), caspase-9 (P < .05) and caspase-3/7 (P = .22) activities, and decreased ATP levels (P < .0001). MOE significantly increased both the expression of Smac/DIABLO protein and cleavage of PARP-1, resulting in an increase in the 24-kDa fragment (P < .001). MOE possesses antiproliferative effects on SNO EC cells by increasing lipid peroxidation, DNA fragmentation, and induction of apoptosis.

  12. Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell.

    Science.gov (United States)

    Fang, Lin; Cheng, Qian; Liu, Wenshun; Zhang, Jie; Ge, Yan; Zhang, Qi; Li, Liantao; Liu, Junjie; Zheng, Junnian

    2016-06-02

    ASBTARCT Adenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35-ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber-modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy.

  13. Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; De-Bing Xiang; Yu-Jun He; Zeng-Peng Li; Xiao-Hua Wu; Jiang-Hong Mou; Hua-Liang Xiao; Qing-Hong Zhang

    2005-01-01

    AIM: To study the effect of caffeic acid phenethyl ester (CAPE)on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116.METHODS: HCT116 cells were treated with CAPE at serial concentrations of 80, 40, 20, 10, 5, 2.5 mg/L. The proliferative status of HCT116 cells was measured by using methabenzthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method.β-catenin levels were determined by Western blotting.β-catenin localization in HCT116 was determined by indirect i mmunofluorescence.RESULTS: After HCT116 cells were exposed to CAPE (80,40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L)for 24 h. CAPE treatment was associated with decreased cytoplasmic β-catenin, nuclear β-catenin and a concurrent increase in β-catenin protein expression at cell-cell junctions.CONCLUSION: CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased β-catenin protein expression may mediate the anti-proliferative effects of CAPE.

  14. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Park, Sung-Bin; Kim, Byungtak; Bae, Hansol; Lee, Hyunkyung; Lee, Seungyeon; Choi, Eun H; Kim, Sun Jung

    2015-01-01

    Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  15. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Sung-Bin Park

    Full Text Available Cold atmospheric plasma (plasma has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05 by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  16. Growth inhibitory effects of Phyllanthus niruri extracts in combination with cisplatin on cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Raimundo Fernandes de Araújo Júnior; Luiz Alberto Lira Soares; Cínthia Raquel da Costa Porto; Ranniere Gurgel Furtado de Aquino; Hugo Gon(c)alo Guedes; Pedro Ros Petrovick; Tatiane Pereira de Souza

    2012-01-01

    AIM:To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cisplatin on two cancer cell lines.METHODS:Colorectal carcinoma (HT29) and human hepatocellular carcinoma (HepG2) cells were treated with spray-dried extracts of Phy//anthus niruri (SDEPN) either alone or in combination with cisplatin at different concentrations (0.5 mg/mL and 1 mg/mL) for 4 h and 24 h.To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability,we stained the cells with propidium iodide and assessed them by flow cytometry.The percentage of cells in different cell cycle phases was quantified and data were expressed as histograms.Significant differences between groups were determined using analysis of variance and Bonferroni's test,as indicated.A value of P < 0.05 was considered to be statistically significant.RESULTS:SDEPN had significantly different cytotoxic effects on HT29 (2.81 ± 0.11 vs 3.51 ± 1.13,P > 0.05) and HepG2 (5.07 ± 0.3 vs 15.9 ± 1.04,P <0.001) cells when compared to control cells for 4 h.SDEPN also had significantly different cytotoxic effects on HT29 (1.91 ± 0.57 vs 4.53 ± 1.22,P > 0.05) and HepG2 (14.56 ± 1.6 vs 35.67 ± 3.94,P < 0.001) cells when compared to control cells for 24 h.Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells (HepG2 cells for 4 h:10.78 ± 1.58 vs 53.89 ± 1.53,P < 0.001; 24 h:8.9 ± 1.43 vs 62.78 ± 1.87,P < 0.001 and HT29 cells for 4 h:9.52 ± 0.913 vs 49.86 ± 2.89,P < 0.001; 24 h:11.78 ± 1.05 vs 53.34 ± 2.65,P < 0.001).In HT29 cells,pretreatment with SDEPN and subsequent treatment with cisplatin resulted in a greater number of cells being killed (12.78 ± 1.01 vs 93.76 ± 1.6,P < 0.001).HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin (12.87±2.78 vs 78.8 ± 3.02,P < 0.001).CONCLUSION:SDEPN is selectively toxic

  17. The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines.

    Science.gov (United States)

    Abdel-Latif, Ghada A; Al-Abd, Ahmed M; Tadros, Mariane G; Al-Abbasi, Fahad A; Khalifa, Amany E; Abdel-Naim, Ashraf B

    2015-07-09

    Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in HER-2 receptor positive and HER-2 receptor negative breast cancer cell lines (T47D and MCF-7 cell lines, respectively). The IC50's of herceptin in T47D and MCF-7 were 0.133 ± 0.005 ng/ml and 23.3795 ± 1.99 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.052 ± 0.001 and 0.0365 ± 0.001 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of BCL-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of HER-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the contrary, herceptin/didox combination had no significant effect on HER-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following all treatments. In conclusion, herceptin/resveratrol and herceptin/didox combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.

  18. Effect of ionizing radiation on transcription of colorectal cancer MDR1 gene of HCT-8 cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Li; Lin Ma; Jing Lu; Li-Xia Kong; Xiao-Hua Long; Su-Huan Liao; Bao-Rong Chi

    2013-01-01

    Objective: To discuss effect of ionizing radiation on transcription of colorectal cancer multidrug resistance (MDR) 1 gene of HCT-8 cells. Methods: Total RNA was extracted by guanidine thiocyanate one-step method. Northern blot was applied to detect transcription level of MDR1 gene. The expression of P-gp protein was detected by flow cytometry. Results: The expression of MDR1 of normal colorectal cancer HCT-8 cells was low. It was increased by 8.35 times under stimulus with 2 Gy. When treated with low doses in advance, high expressed MDR was decreased significantly under 0.05, 0.1 Gy, which was 69.00%, 62.89% in 2 Gy group and 5.77 times, 5.25 times in sham irradiation group. No obvious difference was detected between (0.2+2) Gy group and 2 Gy group. Compared with sham irradiation group, the percentage of P-gp positive cells after radiation of a high 2 Gy dose was increased significantly (P<0.01). When treated with high radiation dose following low radiation dose (0.05 Gy, 0.1 Gy) in advance, the percentage of P-gp positive cells were also increased significantly. The percentage of P-gp positive cells were increased obviously in 0.2 Gy and 2 Gy groups. Compared with simple high radiation 2 Gy group, the percentage of P-gp positive cells was decreased significantly (P<0.05). Conclusions:Low radiation dose can reverse multidrug resistance of colorectal cancer cells caused by high radiation dose.

  19. Chemotherapeutic activities of Carthami Flos and its reversal effect on multidrug resistance in cancer cells.

    Science.gov (United States)

    Wu, Jimmy Yiu-Cheong; Yu, Zhi-Ling; Fong, Wang-Fun; Shi, Yi-Qian

    2013-01-01

    Multidrug-resistance (MDR) represents a major cause of failure in cancer chemotherapy. The need for a reduction in MDR by natural-product-based drugs of low toxicity led to the current investigation of applying medicinal herbs in future cancer adjuvant therapy. Carthami Flos (CF), the dried flower of safflower (Carthamus tinctorius L.), is one of the most popular traditional Chinese medicinal herbs used to alleviate pain, increase circulation, and reduce blood-stasis syndrome. The drug resistance index of the total extract of CF in MDR KB-V1 cells and its synergistic effects with other chemotherapeutic agents were studied. SRB cell viability assays were used to quantify growth inhibition after exposure to single drug and in combinations with other chemotherapeutic agents using the median effect principle. The combination indexes were then calculated according to the classic isobologram equation. The results revealed that CF showed a drug resistance index of 0.096. In combination with other chemotherapeutic agents, it enhanced their chemo-sensitivities by 2.8 to 4.0 folds and gave a general synergism in cytotoxic effect. These results indicate that CF could be a potential alternative adjuvant antitumour herbal medicine representing a promising approach to the treatment of some malignant and MDR cancers in the future.

  20. Interaction between the cytostatic effects of quercetin and 5-fluorouracil in two human colorectal cancer cell lines

    NARCIS (Netherlands)

    Boersma, H H; Woerdenbag, H J; Bauer, Joseph; Scheithauer, W; Kampinga, H H; Konings, A W

    1994-01-01

    Therapy with 5-fluorouracil (5-FU) as a single agent has only limited success in palliative treatment of cancer of the large bowel. In the current study, the effect of quercetin on the action of 5-FU in the human colorectal cancer cell lines COLO 320 DM and COLO 205 was evaluated using the MTT and c

  1. Apoptosis-Inducing Effect of Three Medicinal Plants on Oral Cancer Cells KB and ORL-48

    Directory of Open Access Journals (Sweden)

    Mohd Zabidi Majid

    2014-01-01

    Full Text Available Brucea javanica, Azadirachta indica, and Typhonium flagelliforme are medicinal plants commonly used to treat conditions associated with tumour formation. This study aimed to determine the antiproliferative activity of these plants extracts on KB and ORL-48 oral cancer cell lines and to suggest their mode of cell death. The concentration producing 50% cell inhibition (IC50 was determined and the activity was examined under an inverted microscope. Immunohistochemistry fluorescent staining method (TUNEL was performed to indicate the mechanism of cell death and the fragmented DNA band pattern produced was obtained for verification. Compared to Azadirachta sp. and Typhonium sp., the antiproliferative activity of Brucea sp. extract was the most potent on both KB and ORL-48 cells with IC50 of 24.37 ± 1.75 and 6.67 ± 1.15 µg/mL, respectively. Signs of cell attrition were observed 24 hr after treatment. Green fluorescent spots indicating cell death by apoptosis were observed in images of both cells following treatment with all the three extracts. DNA fragments harvested from Brucea-treated cells produced bands in a ladder pattern suggesting the apoptotic effect of the extract. It is thus concluded that Brucea sp. extract exhibited cytotoxic activity on ORL-48 cells and their action mechanism is via apoptosis.

  2. Effect of free fatty acids and lysolipids on cellular uptake of doxorubicin in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Rasmussen, Nicolaj; Andersen, Jonas; Jespersen, Henrik

    2010-01-01

    Several fatty acids and lysolipids have been shown earlier to increase the permeability of membranes of artificial liposomes, thereby increasing the release of drugs such as doxorubicin (Dox) contained within them. Free fatty acids can also inhibit cancer cell growth in vitro, and it has been......, the liposome could deliver membrane permeability enhancers in addition to the drug to increase the targeted anticancer effect. In this study, we examined the effect on Dox uptake in the breast cancer cell lines MDA-MB-231, MCF7, and MCF7-MDR when incubated with a large panel of different free fatty acids...... and lysolipids. Dox uptake was quantified by flow cytometry and fluorescence microscopy. We observed no increased Dox uptake in any of the breast cancer cell lines, suggesting that growth inhibitory effects observed earlier subsequent to the addition of free fatty acids to cancer cells are not caused...

  3. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    C. E. Storniolo

    2016-12-01

    Full Text Available The mediterranean diet (MD reduced the risk of colorectal cancer (CRC, and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development.

  4. Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Su-Gang Shen; Dong Zhang; Heng-Tong Hu; Jun-Hui Li; Zheng Wang; Qing-Yong Ma

    2008-01-01

    AIM: To discuss the expression of α-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of α1- and α2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro.METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of α1- and α2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR).The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleoticlyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM).RESULTS: PC-2 expressed rnRNA in α1- and α2-adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However,exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine.Cell proliferation was inhibited by yohimbine via apoptosis induction.CONCLUSION: The expression of α1-and α2-adrenoreceptors is different in PC-2 and PC-3 cell lines,which might be indicative of their different functions. Theα2-adrenoceptor antagonist, yohimbine, can inhibit the proliferation of both cell lines and induce their apoptosis,suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells.

  5. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Science.gov (United States)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  6. Chemical constituents and antiproliferative effects of cultured Mougeotia nummuloides and Spirulina major against cancerous cell lines.

    Science.gov (United States)

    Erenler, Ramazan; Pabuccu, Koksal; Yaglioglu, Ayse Sahin; Demirtas, Ibrahim; Gul, Fatih

    2016-03-01

    In this study, the effect of Mougeotia nummuloides and Spirulina major on Vero cells (African green monkey kidney), C6 cells (rat brain tumor cells) and HeLa cells (human uterus carcinoma) was investigated in vitro. The antiproliferative effect of the methanol extract of M. nummuloides and S. major compared with 5-fluorourasil (5-FU) and cisplatin was tested at various concentrations using the BrdU Cell Proliferation ELISA. Both M. nummuloides and S. major extracts significantly inhibited the proliferation of Vero, HeLa and C6 cancer cell lines with IC50 and IC75 values. The M. nummuloides extract exhibited higher activity than 5-FU and cisplatin on Vero and C6 cells at high concentrations. The S. major extract revealed better antifproliferative activity than standards against Vero cells at 500 μg/mL. The compounds of methanol extracts were determined by GC-MS after the silylation process. Trehalose, monostearin and 1-monopalmitin were detected as major products in the M. nummuloides extract where as in the S. major extract; monostearin, 1-monopalmitin and hexyl alcohol were the main constituents.

  7. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status

    Indian Academy of Sciences (India)

    DAIANE TEIXEIRA DE OLIVEIRA; ANDRÉ LUIZ VENTURA SÁVIO; JOÃO PAULO DE CASTRO MARCONDES; TATIANE MARTINS BARROS; LUDMILA CORREIA BARBOSA; DAISY MARIA FAVERO SALVADORI; GLENDA NICIOLI DA SILVA

    2017-03-01

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness forpreventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activityof silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used:RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates,genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 andmiR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutatedcells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survivalassay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 andmiR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion,despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR,AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role ofsilibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.

  8. Generation of Novel Thyroid Cancer Stem-Like Cell Clones: Effects of Resveratrol and Valproic Acid.

    Science.gov (United States)

    Hardin, Heather; Yu, Xiao-Min; Harrison, April D; Larrain, Carolina; Zhang, Ranran; Chen, Jidong; Chen, Herbert; Lloyd, Ricardo V

    2016-06-01

    Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies.

  9. Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Toshiyuki Ishiwata; Yoko Matsuda; Zenya Naito

    2011-01-01

    Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

  10. The Effects of High Concentrations of Vitamin C on Cancer Cells

    Directory of Open Access Journals (Sweden)

    Seyeon Park

    2013-09-01

    Full Text Available The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25–1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation.

  11. Effects of bleomycin and antioxidants on the fatty acid profile of testicular cancer cell membranes.

    Science.gov (United States)

    Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A

    2016-02-01

    Bleomycin is used in chemotherapy regimens for the treatment of patients having testicular germ-cell tumor (TGCT). There is no study in the literature investigating the effects of bleomycin on membrane lipid profile in testicular cancer cells. We investigated membrane fatty acid (FA) profiles isolated, derivatized and analyzed by gas chromatography of NTera-2 testicular cancer cells incubated with bleomycin (Bleo) for 24 h in the absence and presence of N-Acetyl-L-Cysteine (NAC) and curcumin (Cur) as commonly used antioxidant adjuvants. At the same time the MAPK pathway and EGFR levels were followed up. Bleomycin treatment increased significantly saturated fatty acids (SFA) of phospholipids at the expense of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Bleomycin also led to a significant increase in the trans lipid isomers of oleic and arachidonic acids due to its free radical producing effect. Incubation with bleomycin increased the p38 MAPK and JNK levels and downregulated EGFR pathway. Coincubation of bleomycin with NAC reversed effects caused by bleomycin. Our results highlight the important role of membrane fatty acid remodeling occurring during the use of bleomycin and its concurrent use with antioxidants which can adjuvate the cytotoxic effects of the chemotherapeutic agents.

  12. Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells.

    Directory of Open Access Journals (Sweden)

    Loredana Alberti

    Full Text Available Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites or CTCFL (CTCF-like is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1 and cancer stem cell markers (ABCG2, CD44 and ALDH1 genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7. Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells.

  13. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake

    DEFF Research Database (Denmark)

    Lund, E L; Quistorff, B; Spang-Thomsen, M;

    1998-01-01

    The effect of oral ubiquinone (Q10) intake on the in vivo response of tumors to single dose radiotherapy was examined. The human small-cell lung cancer (SCLC) line CPH 054A, which is sensitive to relatively low doses of X-radiation, was grown as subcutaneous transplants in the flanks of nude nu...... radiation dose of 5 Gy, using a 300 kV therapeutic unit. The macroscopic growth pre- and posttreatment was analyzed according to a transformed Gompertz algorithm using the software program GROWTH. Treatment with Q10 or soy oil alone had no effect on tumor growth compared with untreated controls. Groups...

  14. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Matthew A Ingersoll

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

  15. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Muniyan, Sakthivel; D’Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G.; Bu, Xiu R.; Batra, Surinder K.; Lin, Ming-Fong

    2015-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents. PMID:26121643

  16. Cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells

    Directory of Open Access Journals (Sweden)

    Sajjadi Seyed Ebrahim

    2015-01-01

    Full Text Available Introduction: Little information is available about phytochemical and biological properties of Cousinia genus. In a primary study, seven Cousinia species including C. verbascifolia showed cytotoxic activity ranged between 18.4 ± 0.59 to 87.9 ± 0.58 μg/mL. To the best of our knowledge, no other biological studies have been conducted on this plant. Therefore, in this study the cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells was evaluated. Methods: Filtration and in vacuo concentration of methanol extract resulted in a green gum which was subjected on reverse column chromatography. Semi polar fraction (41.3 g eluted with water: methanol (20:80, was then subjected on a silica gel column chromatography using hexane/acetone and resulted in 11 fractions. Finally, cytotoxic activities against ovarian and colon cancer cells were determined at a wavelength of 570 nm by Matrix metalloproteinase protein (MTT standard method. Results: None of the fractions showed highly cytotoxic activity. Based on NCI, fractions Fr. 1, Fr. 2, Fr. 4, Fr. 5, Fr. 6, Fr. 8 and Fr. 10 showed moderately cytotoxicity with IC50 values ranged between 119 to 190 μg/mL against OVCAR-3 cells. Fractions Fr. 1, Fr. 2, Fr. 6, Fr. 7 and Fr. 8 showed moderately cytotoxic activity ranged between 118 to 194 μg/mL against HT-29 cells. Fr. 10 and Fr. 11 showed no cytotoxic activity. Conclusion: Due to the inhibitory properties of extract and its fractions on cancer cells, identification of responsible compounds possessing cytotoxic effects for generating possible new approach in medicinal chemistry are recommended.

  17. Synergistic antitumor effect of TRATL and doxorubicin on colon cancer cell line SW480

    Institute of Scientific and Technical Information of China (English)

    Li-Hong Xu; Chang-Sheng Deng; You-Qing Zhu; Shi-Quan Liu; Dong-Zhou Liu

    2003-01-01

    AIM: TRAIL (tumor necrosis factor-related apoptosisinducing ligand) has been reported to specifically induce apoptosis of cancer cells although only a small percentage of cell lines were sensitive to it. Cell lines not responding to TRAIL in vitro were said to be more prone to apoptosis when TRAIL was combined with another anticancer agent.Generally, factors affecting drug-sensitivity involve many apoptosis-related proteins, including p53. The expression of wild-type p53 gene was proposed as an important premise for tumor cells responding to chemotherapy. The present study was to investigate the cell killing action of TRAIL on colon cancer cell line SW480, its synergistic effect with doxorubicin, and the possible mechanisms. METHODS: SW480 cells were cultured in the regular condition and incubated with different levels of agents.Morphologic changes in these cells after treatment were observed under phase-contrast microscope and cytotoxicity by TRAIL alone and in combination with doxorubicin was quantified by a 1-day microculture tetrazolium dye (MTT)assay. In addition, flow cytometry assay (FCM) and transmission electron microscopy were used to detectapoptosis among these cells. Variation of p53 protein level among different groups according to concentrations of agents was measured by Western blot assay.RESULTS: (1) SW480 cells were not sensitive to TRAIL,with IC50>1 mg@L1 and dose-independent cytotoxicity. (2)SW480 cells were sensitive to doxorubicin at a certain degree,with dose-dependent cytotoxicity and IC50=65.25+3.48μmol@L-1. (3) TRAIL could synergize with doxorubicin to kill SW480 cells effectively, which was represented by the boosted killing effect of doxorubicin on theses cells. IC50 of doxorubicin against SW480 cells sharply reduced when it was combined with TRAIL. (4) Subtoxic TRAIL (100 μg.L-1),combined with subtoxic doxorubicin (0.86 μmol@L1), could kill SW480 cells sufficiently. Cytotoxicity by MTT assay arrived at 80.12+2.67%, which was

  18. Antiproliferative effects of copper(II)-polypyridyl complexes in breast cancer cells through inducing apoptosis.

    Science.gov (United States)

    Salimi, Mona; Abdi, Khatereh; Kandelous, Hirsa Mostafapour; Hadadzadeh, Hassan; Azadmanesh, Kayhan; Amanzadeh, Amir; Sanati, Hassan

    2015-04-01

    Although cisplatin has been used for decades to treat human cancer, some toxic side effects and resistance are observed. Previous investigations have suggested copper complexes as a novel class of tumor-cell apoptosis inducers. The present study aimed to evaluate the anti-breast cancer activities of two polypyridyl-based copper(II) complexes, [Cu(tpy)(dppz)](NO3)2 (1) and [Cu(tptz)2](NO3)2 (2) (tpy = 2,2':6',2″-terpyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine, tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine), using human breast adenocarcinoma cell line (MCF-7). The ability of the complexes to cleave supercoiled DNA in the presence and absence of external agents was also examined. The apoptotic activities of the complexes were assessed using flow cytometry, fluorescence microscope and western blotting analysis. Our results indicated the high DNA affinity and nuclease activity of complexes 1 and 2. The cleavage mechanisms between the complexes and plasmid DNA are likely to involve a singlet oxygen or singlet oxygen-like entity as the reactive oxygen species. Complexes 1 and 2 also significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner (IC50 values = 4.57 and 1.98 μM at 24 h, respectively). Complex 2 remarkably induced MCF-7 cells to undergo apoptosis, which was demonstrated by cell morphology, annexin-V and propidium iodide staining. The caspase cascade was activated as shown by the proteolytic cleavage of caspase-3 after treatment of MCF-7 cells with complex 2. Additionally, complex 2 significantly increased the expression of the Bax-to-Bcl-2 ratio to induce apoptosis. In conclusion, these results revealed that complex 2 may be a potential and promising chemotherapeutic agent to treat breast cancer.

  19. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype

    Institute of Scientific and Technical Information of China (English)

    Jing Ye; Yun-Lin Wu; Shu Zhang; Zi Chen; Li-Xia Guo; Ruo-Yu Zhou; Hong Xie

    2005-01-01

    AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901)and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism,and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells.METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay.RESULTS: Telomerase activity was detected in well,moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively).Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 μmol/L, and was entirely inhibited at 10 μmol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901gastric cancer cell lines (the inhibition ratio was 40.89%and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0

  20. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells

    Science.gov (United States)

    Cha, Jae Hoon; Kim, Woo Kyoung; Ha, Ae Wha; Kim, Myung Hwan

    2017-01-01

    BACKGROUND/OBJECTIVES Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and 30 µM lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B (NF-κB), inhibitor kappa B (IκB), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) were determined via enzyme-linked immunosorbent assays. RESULTS In cells treated with lycopene and LPS, the mRNA expression of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P cancer cells.

  1. Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

    Science.gov (United States)

    Benavente, Micaela Andrea; Bianchi, Carolina Paula; Imperiale, Fernanda; Aba, Marcelo Alfredo

    2016-01-01

    Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient’s overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 103 and 8 × 103 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 103 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 103 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 103 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 103 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis. PMID:28083539

  2. Effects of Curcumin on Invasion and Metastasis in the Human Cervical Cancer Cells Caski

    Institute of Scientific and Technical Information of China (English)

    Fang XU; Xiao-ling MU; Jing ZHAO

    2009-01-01

    Objective: To explore the effects of curcumin on invasion and metastasis in the human cervical cancer cells Caski.Methods: Caski cells were treated with 10, 25, 50μmol/L curcumin for 24, 48, 72 h. Proliferation of Caski cells was measured with MTT assay. When treated with 50μmol/L curcumin for 72 h, the expressions of MMP-2, MT1-MMP and NF-κB of cells were detected by Western-blot, and invasion and metastasis of Caski cells were evaluated with transwell chamber.Results: After being treated with 10μmol/L, 25μmol/L, 50μmol/L curcumin for 24, 48 and 72 h, the proliferation of Caski cells was inhibited in a dose-and time-dependent manner. The expression of MMP-2, MT1-MMP and NF-κB were decreased when being treated with 50μmol/L curcumin for 72 h. After treatment with 50μmol/L curcumin, in invasion assay, the number of cells in curcumin treated group to migrate to filter coated with Matrigel was reduced compared with control group(P<0.05). Meanwhile, in migration assay, the number of cells in curcumin treated group to migrate to filter was also decreased compared with control group (P<0.05).Conclusion: Curcumin could affect the invasion and metastasis of the human cervical cancer cells Caski. Inhibiting the expression of MMP-2, MT1-MMP and NF-κB was probably one of its molecular mechanisms.

  3. TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.

    Directory of Open Access Journals (Sweden)

    V'yacheslav Lehen'kyi

    Full Text Available Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007. However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enhances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies.

  4. Potential Anti-proliferative and Immunomodulatory Effects of Marine Microalgal Exopolysaccharide on Various Human Cancer Cells and Lymphocytes In Vitro.

    Science.gov (United States)

    Park, Geon-Tae; Go, Ryeo-Eun; Lee, Hae-Miru; Lee, Geum-A; Kim, Cho-Won; Seo, Jeong-Woo; Hong, Won-Kyung; Choi, Kyung-Chul; Hwang, Kyung-A

    2017-02-04

    Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment. Alterations in immunoreactivity by the microalgal EPS were examined by measuring its influence on the growth of T and B lymphocytes and cytokine production of T cells. In cell viability assay, the microalgal EPS inhibited cancer cell growth at the lowest concentration of 10(-11) dilution and in a dose-responsive manner within the range of dilution of 10(-11)~10(-3). In addition, the protein expression of cell cycle progression genes such as cyclin D1 and E in these cancer cell lines was significantly reduced by the microalgal EPS in a dose- and a time-dependant manner. In cell proliferation assay using T and B cells, the microalgal EPS induced B cell proliferation even at the lowest dilution of 10(-11), but not T cells. In cytokine assay, the microalgal EPS decreased the formation of IL-6 and INF-γ at 10(-3) dilution compared to the control and had no significant effects on TNF-α. Collectively, these findings suggest that the EPS derived from microalgae Thraustochytriidae sp. GA has an anti-proliferative activity against cancer cells and an immunomodulatory effect by having an influence on B cell proliferation and cytokine secretion of T cells.

  5. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an a

  6. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Abhilash Samykutty

    Full Text Available Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP. Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these

  7. Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.

    Science.gov (United States)

    Chang, Kee-Lung; Cheng, Hsiao-Ling; Huang, Li-Wen; Hsieh, Bau-Shan; Hu, Yu-Chen; Chih, Tsai-Tung; Shyu, Huey-Wen; Su, Shu-Jem

    2009-04-08

    Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

  8. Time course of effects of chemotherapy and radiotherapy on a human pancreatic cancer cell line (SUIT-2) in vitro

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    Wakasugi, Hideyuki; Seo, Yohsuke; Yamada, Yukio; Hata, Kazuo; Higuchi, Kaoru; Kohno, Akira [National Kyushu Cancer Center, Fukuoka (Japan)

    1995-03-01

    In order to investigate time course of effects of chemotherapy and radiotherapy on pancreatic cancer, we used the monolayer culture of a human pancreatic cancer cell line, SUIT-2 which produces CEA and CA19-9. Into the culture various kinds of anti-cancer drugs (MMC, ADR, FAR, 5FU, FT, CDDP, CPT-11) were administered for a period of 2 days, followed by irradiation with {sup 60}Co. Observation period was 20 days, during which we measured LDH, CEA and Ca19-9 in medium, DNA, protein, CEA and CA19-9 in cells in addition to observation of cells through microscope. Effects of anti-cancer drugs on pancreatic cancer cells were greater than those of irradiation when doses of anti-cancer drugs were enough. By using a lot of anti-cancer drugs, LDH value in medium increased at early time and decreased later. CEA and Ca19-9 values in medium decreased with the lapse of time, while they were increased later when small doses of the drugs had been administered. DNA, protein, CEA and Ca19-9 values in cells showed a decrease in accordance with increased doses of the drugs. Effects of FT and CPT-11 were marginal compared with the other drugs. (author).

  9. Effects of HMGA2 on malignant degree, invasion, metastasis, proliferation and cellular morphology of ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Ni Xi; Xiao-Yan Xin; Hong-Mei Ye

    2014-01-01

    Objective: To analyze effects of high mobility group AT-hook 2 (HMGA2) on malignant degree, invasion, metastasis, proliferation and cellular morphology of ovarian cancer cells. Methods:Three methods were applied to observe the effect on HMGA2 expression in ovarian cancer cells and ovarian epithelial cells. Results: After the application of siRNA-HMGA2, number of T29A2-cell clones was decreased, there was significant difference compared with the negative control Block-iT. After application of let-7c, number of T29A2+ cell clones was decreased significantly, however, after the application of Anti-let-7, the number of clones restored, and there was no significant difference compared with the negative control group. After interference, the number of T29A2- cells which passed through Matrigel polycarbonate membrane were significantly lower than the negative control group. After the treatment of siRNA-HMGA2, let-7c and sh-HMGA2 respectively, growth and proliferation of T29A2-, T29A2+ and SKOV3 were slower, and the phenomenon was most obvious in SKOV3. Stable interference of HMGA2 induced mesenchymal-epithelial changes in the morphology of SKOV3-sh-HMGA2. Conclusions: HMGA2 can promote malignant transformation of ovarian cancer cells, enhance cell invasion and metastasis, and promote cell growth and proliferation of ovarian cancer cells, which can cause ovarian cancer to progress rapidly and affect the quality of life.

  10. Expression of nucleostemin in prostate cancer and its effect on the proliferation of PC-3 cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Nucleostemin is essential for the proliferation and survival of stem and cancer cells,but it is unknown whether this newly identified molecule is involved in prostate cancer pathogenesis.Methods Total RNA and protein were extracted from prostate cancer tissues and PC-3,LNCap and DU145 cell lines.The nucleostemin mRNA and protein expression were measured by RT-PCR and Western blot.Immunohistochemistry was also used to detect the nucleostemin protein expression in prostate cancer tissues and PC-3 cells.A nucleostemin specific,short hairpin RNA,expression plasmid was used to transfect PC-3 cells.The changes of nucleostemin gene were detected and the proliferative capacity of the cells was determined.Results Nucleostemin was highly expressed in prostate cancer tissues and cell lines.Nucleostemin expression level in the silencer group PC-3 cells remarkably reduced.The proliferation rate of silencer group PC-3 cells decreased and the percentage of G1 stage cells increased.The neoplasm forming capacity in nude mice of the silencer group PC-3 cells decreased significantly.Conclusions Nucleostemin is highly expressed in prostate cancer tissues and cell lines.The proliferative capacity of PC-3 cells is remarkably reduced after silencing nucleostemin gene expression.

  11. Combination Effects of Docetaxel and Doxorubicin in Hormone-Refractory Prostate Cancer Cells

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    Eleftheria Tsakalozou

    2012-01-01

    Full Text Available Combination effects of docetaxel (DOC and doxorubicin (DOX were investigated in prostate cancer cells (PC3 and DU145. Combination indices (CIs were determined using the unified theory in various concentrations and mixing ratios (synergy: CI1.1. DOC showed a biphasic cytotoxicity pattern with the half maximal inhibitory concentration (IC50 at the picomolar range for PC3 (0.598 nM and DU145 (0.469 nM, following 72 h drug exposure. The IC50s of DOX were 908 nM and 343 nM for PC3 and DU145, respectively. Strong synergy was seen when PC3 was treated with DOC at concentrations lower than its IC50 values (0.125~0.5 nM plus DOX (2~8 times IC50. Equipotent drug combination treatments (7×7 revealed that the DOC/DOX combination leads to high synergy and effective cell death only in a narrow concentration range in DU145. This study provides a convenient method to predict multiple drug combination effects by the estimated CI values as well as cell viability data. The proposed DOC/DOX mixing ratios can be used to design combination drug cocktails or delivery systems to improve chemotherapy for cancer patients.

  12. CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

    Science.gov (United States)

    Siddiqui, Y H; Kershaw, R M; Humphreys, E H; Assis Junior, E M; Chaudhri, S; Jayaraman, P-S; Gaston, K

    2017-01-01

    PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion. PMID:28134934

  13. Inhibitive effect of IL-24 gene on CD133+laryngeal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jin-Zhang Cheng; Dan Yu; Hui Zhang; Chun-Shun Jin; Yan Liu; Xue Zhao; Xin-Meng Qi; Xueshi-Bojie Liu

    2014-01-01

    Objective:To explore the inhibitive and apoptosis inductive effect of IL-24 genes on CD133+laryngeal cancer cells in Hep-2 line. Methods: Human peripheral blood monocytes were isolated. The total RNA was extracted by using Trizol method and reverse transcripted into cDNA using RT-PCR method. Primers P1 and P2 was designed for the amplification of human IL-24 genes. After confirmation of agarose gel electrophoresis tests, TA was cloned into pMD19-T simple vector. NheⅠand XhoⅠdouble digesting human IL-24 and pIRES2-ZsGreen1 and eukaryotic expression vector were used to establish the pIRES2-ZsGreen1-hIL-24 vector, and detected by enzyme digestion and gene sequencing methods. Flow cytometry (FCM) was used to isolate CD133+cells from Hep-2 cells. CD133+cells were transfected with pIRES2-ZsGreen1-hIL-24 through liposome 2000. After detection, MTT and FCM were used to observe the effect of IL-24 gene on CD133+laryngeal cancer Hep-2 cells. Results: Lipotin mediated transfection of recombinant pIRES2-ZsGreen1-hIL-24 plasmid into CD133+Hep-2 could expressed IL-24 gene in cells stably. MTT results showed that IL-24 transfected group was significantly suppressed compared to empty vector group and control group (P<0.05); FCM results showed that the apoptosis rate of experimental group increased significantly compared to empty vector group and control group (P<0.05). Conclusions:IL-24 gene expressions can inhibit proliferation of CD133+laryngeal cells in Hep-2 line and promote their apoptosis.

  14. Effect of Estrogen on Telomerase Activity in Human Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    高金波; 陈道达; 田元; 张锦辉; 蔡开琳

    2003-01-01

    To investigate the effects of estrogen(E2 ) on telomerase activity and its mechanism inhuman breast cancer cells, estrogen receptor positive MCF-7 cells were treated with different con-centrations of E2. Telomerase activity was measured by using TRAP-ELISA method, the cell cyclephases analyzed by using flow cytometry, and the expression of Cyclin D1 detected by using immu-nohistochemistry method. The results showed that telomerase activity levels were increased inMCF-7 cells treated with 10-8 mol/L E2 during the observed period (P<0.05), and E2 increasedtelomerase activity levels in a dose-dependent manner(10-10- 10-8 mol/L); Simultaneously, thecell cycle phases of MCF-7 cells treated with 10-8 mol/L E2 were changed significantly: G0/G1phase decreased from 60.52% to 50. 93%, S phase increased from 29.03% to 30.83%; However,the expression of Cyclin D1 was decreased. It was concluded that estrogen can upregulate telomeraseactivity of MCF-7 cells, and the effect can be blocked by antiestrogen tamoxifen. Its mechanismmay be closely associated with modulation of cell cycle phases.

  15. FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review).

    Science.gov (United States)

    Katoh, Masaru

    2016-07-01

    Fibroblast growth factor (FGF)2, FGF4, FGF7 and FGF20 are representative paracrine FGFs binding to heparan-sulfate proteoglycan and fibroblast growth factor receptors (FGFRs), whereas FGF19, FGF21 and FGF23 are endocrine FGFs binding to Klotho and FGFRs. FGFR1 is relatively frequently amplified and overexpressed in breast and lung cancer, and FGFR2 in gastric cancer. BCR-FGFR1, CNTRL-FGFR1, CUX1-FGFR1, FGFR1OP-FGFR1, MYO18A-FGFR1 and ZMYM2-FGFR1 fusions in myeloproliferative neoplasms are non-receptor-type FGFR kinases, whereas FGFR1-TACC1, FGFR2-AFF3, FGFR2-BICC1, FGFR2-PPHLN1, FGFR3-BAIAP2L1 and FGFR3-TACC3 fusions in solid tumors are transmembrane-type FGFRs with C-terminal alterations. AZD4547, BGJ398 (infigratinib), Debio-1347 and dovitinib are FGFR1/2/3 inhibitors; BLU9931 is a selective FGFR4 inhibitor; FIIN-2, JNJ-42756493, LY2874455 and ponatinib are pan-FGFR inhibitors. AZD4547, dovitinib and ponatinib are multi-kinase inhibitors targeting FGFRs, colony stimulating factor 1 receptor (CSF1R), vascular endothelial growth factor (VEGF)R2, and others. The tumor microenvironment consists of cancer cells and stromal/immune cells, such as cancer-associated fibroblasts (CAFs), endothelial cells, M2-type tumor-associating macrophages (M2-TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells. FGFR inhibitors elicit antitumor effects directly on cancer cells, as well as indirectly through the blockade of paracrine signaling. The dual inhibition of FGF and CSF1 or VEGF signaling is expected to enhance the antitumor effects through the targeting of immune evasion and angiogenesis in the tumor microenvironment. Combination therapy using tyrosine kinase inhibitors (FGFR or CSF1R inhibitors) and immune checkpoint blockers (anti-PD-1 or anti-CTLA-4 monoclonal antibodies) may be a promising choice for cancer patients. The inhibition of FGF19-FGFR4 signaling is associated with a risk of liver toxicity, whereas the activation of FGF23-FGFR4 signaling

  16. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Directory of Open Access Journals (Sweden)

    Abeer M Mahmoud

    Full Text Available Blocking the androgen receptor (AR activity is the main goal of therapies for advanced prostate cancer (PCa. However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  17. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Science.gov (United States)

    Mahmoud, Abeer M; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C

    2013-01-01

    Blocking the androgen receptor (AR) activity is the main goal of therapies for advanced prostate cancer (PCa). However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent) activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A) mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L) stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  18. Effects of MSH2 gene re-expression on estrogen induced-apoptosis of colon cancer cells LOVO

    Institute of Scientific and Technical Information of China (English)

    吕晨曦

    2014-01-01

    Objective To observe the effects of MSH2 gene reexpression on estrogen-induced apoptosis of colon cancer cells LOVO,and to explore its mechanisms.Methods According to different plasmid and whether with estradiol intervention,colon cancer LOVO cells were divided into empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with

  19. Inhibitory effect of schisandrin B on gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the inhibitory effect and possible mechanism of action of schisandrin B in SC-B on gastric cancer cells in vitro.METHODS: SC-B consisted of schisandrin B, aloeemodin, and Astragalus polysaccharides. Exponentially growing human gastric cancer SGC-7901 cells were divided into six treatment groups: (1) control group (RPMI 1640 medium); (2) negative control group (2% DMSO);(3) positive control group (50 mg/L 5-Fluorouracil,5-FU); (4) low-dose group (LSC, final concentration of schisandrin B, 25 mg/L); (5) moderate-dose group (MSC,final concentration of schisandrin B, 50 mg/L); (6) high-dose group (HSC, final concentration of schisandrin B,100 mg/L). Follow-up was done at 12-48 h. An MTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was used to examine the inhibitory effect of SC-B on gastric cancer cells. The mitosis index was assessed using an inverted microscope. Flow cytometry was used to visualize the cell cycle. An RT-PCR (Reverse transcription-Polymerase chain reaction) -based assay was used to detect mRNA expression for cyclin D1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).RESULTS: The MTT assay showed that the number of living cells in the LSC, MSC and HSC groups was significantly smaller than that in the DMSO-treated group (P < 0.05) at 12-48 h. The inhibitory rate (IR) of the LSC group was 41.15% ± 3.86%, 59.24% ± 5.34% and 69.93% ± 7.81% at 12, 24 and 48 h, respectively. The IR of the MSC group was 42.82% ± 4.94%, 62.68% ± 7.58% and 71.79% ± 8.12% at 12, 24 and 48 h,respectively. The IR of the HSC group was 37.50% ± 3.21%, 40.34% ± 2.98% and 61.99% ± 4.88% at 12,24 and 48 h, respectively. These results suggested that a moderate dosage had the most obvious inhibitory efficacy at 48 h. Compared to the DMSO group, the mitosis index of the LSC, MSC, HSC groups was greatly decreased (P < 0.05) at all time points. Any dose of SC-B suppressed mitosis within 12-48 h. Compared to the DMSO group, the percentage of cells

  20. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy

    Directory of Open Access Journals (Sweden)

    Zhang XF

    2016-08-01

    Full Text Available Xi-Feng Zhang,1 Sangiliyandi Gurunathan2 1College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of China; 2Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul, South Korea Abstract: Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16–20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL, which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination

  1. Effect of Trastuzumab on Notch-1 Signaling Pathway in Breast Cancer SK-BR3 Cells

    Institute of Scientific and Technical Information of China (English)

    Ming Han; Hua-yu Deng; Rong Jiang

    2012-01-01

    Objective:To investigate the effects and mechanisms of trastuzumab on Notch-1 pathway in breast cancer cells,recognizing the significance of Notch-1 signaling pathway in trastuzumab resistance.Methods:Immunocytochemistry staining and Western blotting were employed to justify the expression of Notch-1 protein in HER2-overexpressing SK-BR3 cells and HER2-non-overexpressing breast cancer MDA-MB-231 cells.Western blotting and reverse transcription PCR (RT-PCR) were used to detect the activated Notch-1 and Notch-1 target gene HES-1 mRNA expression after SK-BR3 cells were treated with trastuzumab.Double immunofluorescence staining and co-immunoprecipitation were used to analyze the relationship of Notch-1 and HER2 proteins.Results:The level of Notch-1 nuclear localization and activated Notch-1 proteins in HER2-overexpressing cells were significantly lower than in HER2-non-overexpressing cells (P<0.01),and the expressions of activated Notch-1 and HES-1 mRNA were obviously increased after trastuzumab treatment (P<1.05),but HER2 expression did not change significantly for trastuzumab treating (P>0.05).Moreover,Notch-1 was discovered to co-localize and interact with HER2 in SK-BR3 cells.Conclusion:Overexpression of HER2 decreased Notch-1 activity by the formation of a HER2-Notch1 complex,and trastuzumab can restore the activity of Notch-1 signaling pathway,which could be associated with cell resistance to trastuzumab.

  2. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  3. Expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xuan-Hong Yi; Jing Wang

    2016-01-01

    Objective:To study the expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines.Methods:Cancer tissue and adjacent normal lung tissue were collected and mRNA contents of Klf8 were detected; lung cancer A549 cell lines were cultured, and after transfection of Klf8 siRNA, cell cycle, cell invasion and epithelial-mesenchymal transition were detected.Results:mRNA contents of Klf8 in lung cancer tissue were higher than those in adjacent normal lung tissue; after transfection of Klf8 siRNA, Klf8 mRNA inhibition rate was 74.31%; G0/G1 phase ratio of Klf8 siRNA group was higher than that of negative control siRNA group; ratios of S-phase and G2/M phase cells, mRNA contents of Cyclin D1 and number of cells invading to the outer side of the transwell microporous membrane were lower than those of negative control siRNA group; mRNA contents of CDH1 and CK18 as well as Snail and Slug of Klf8 siRNA group were higher than those of negative control siRNA group; mRNA contents of VIM and N-cadherin were lower than those of negative control siRNA group.Conclusion:The expression of Klf8 in lung cancer tissue abnormally elevates; downregulation of Klf8 expression in lung cancer cell lines can inhibit malignant biological effect of cells, manifested as cell cycle arrest as well as the inhibition of cell invasion and epithelial-mesenchymal transition processes.

  4. Morphological changes of apoptosis and cytotoxic effects induced by Caffeic acid phenethyl ester in AGS human gastric cancer cell line

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    Amini-Sarteshnizi Nematollah

    2014-04-01

    Full Text Available Introduction: Gastric cancer is the fourth prevalent cancer and the second reason for cancer-associated mortalities worldwide. Caffeic acid phenethyl ester (CAPE is one of the main medicinal components of propolis. The aim of this study was to investigate the morphological apoptotic changes and cytotoxic effects of CAPE in human gastric adenocarcinoma cell line (AGS cell. Methods: AGS human gastric cancer cell line was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM medium in vitro. Cytotoxic effects and morphological changes induced by 72 h treatment with CAPE at different concentrations on AGS cells were investigated by MTT assay test and inverted microscope, respectively. Results: CAPE in a concentration dependent fashion reduced viability of AGS cells. IC50 was obtained approximately 10 μM at 72 h treatment. Also, CAPE induced concentration-dependent morphological apoptotic changes and promoted complete apoptosis program in AGS human gastric cancer cell line. Conclusion: Our results strongly suggest that CAPE stimulates apoptotic process and leads to cell death. Therefore, CAPE could be useful in developing chemotherapeutic agents for treating human gastric cancer.

  5. Effect of ginsenoside Rh-2 via activation of caspase-3 and Bcl-2-insensitive pathway in ovarian cancer cells.

    Science.gov (United States)

    Kim, Jin Hee; Choi, Jae-Sun

    2016-12-13

    Ginsenoside has been reported to have therapeutic effects for some types of cancer, but its effect on ovarian cancer cells has not been evaluated. In this study, we monitored the effects of ginsenoside-Rh2 (Rh2) on the inhibition of cell proliferation and the apoptotic process in the ovarian cancer cell line SKOV3 using an MTT assay and TUNEL assay. We found that Rh2 inhibited cell proliferation and significantly induced apoptosis. We confirmed the apoptotic effects of Rh2 using western blot analysis of apoptosis-related proteins. Specifically, the levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 significantly increased in SKOV3 cells treated with Rh2. Therefore, Rh2 clearly suppressed the growth of SKOV3 cells in vitro, which was associated with induction of the apoptosis pathway. Moreover, the migration assay showed that Rh2 inhibited the invasive ability of SKOV3 cells. Taken together, our results suggest that Rh2 has anticancer effects in SKOV3 cells through inhibition of cell proliferation and induction of apoptosis. Considering the therapeutic potential of Rh2, more studies should be carried out to facilitate the future application of this natural product as a potential anti-cancer agent.

  6. Anti-tumor effect of bisphosphonate (YM529 on non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Date Hiroshi

    2007-01-01

    Full Text Available Abstract Background YM529 is a newly developed nitrogen-containing bisphosphonate (BP classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC. Methods Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157 were measured by MTS assay and calculated inhibition concentration 50 % (IC50 values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method. We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819. Conclusion Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

  7. Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Khanitta Srimuangwong; Chainarong Tocharus; Pornphrom Yoysungnoen Chintana; Apichart Suksamrarn; Jiraporn Tocharus

    2012-01-01

    AIM:To investigate the ability of hexahydrocurcumin (HHC) to enhance 5-fluorouracil (5-FU) in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase (COX)-2 expression.METHODS:Antiproliferative effects of HHC and 5-FU,alone and in combination,on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide (MTT) reduction assay.In combination treatment,low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxicity and side effects of 5-FU.The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis.RESULTS:MTT reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control.Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor.This finding was supported by the observation that HHC significantly down-regulates COX-2 mRNA expression compared to the control (control:100.05% ± 0.03% vs HHC:61.01% ± 0.35%,P < 0.05)but does not alter COX-1 mRNA.In combined treatment,addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy.Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 μmol/L in combination with HHC at the concentration of 25 μmol/L significantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone (HHC + 5-FU:31.93% ± 5.69%,5-FU:100.66%± 4.52% vs HHC:61.01% ± 0.35%,P < 0.05).CONCLUSION:HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.

  8. Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool for cancer cell imaging, targeted drug delivery and synergistic effect of drug and hyperthermia mediated cancer therapy.

    Science.gov (United States)

    Sivakumar, Balasubramanian; Aswathy, Ravindran Girija; Sreejith, Raveendran; Nagaoka, Yutaka; Iwai, Seiki; Suzuki, Masashi; Fukuda, Takahiro; Hasumura, Takashi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthikumar, Dasappan Nair

    2014-06-01

    Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria that have garnered considerable attention and have remarkable potential in various fields, including biomedical research. The necessity of biocompatible materials to coat and stabilize nanoparticles is highly recommended for successful application of the same in biomedical regime. In our study we have coated magnetic nanoparticles (MNPs) with two bacterial EPS-mauran (MR) and gellan gum (GG). The biocompatibility of EPS coated MNPs was enhanced and we have made it multifunctional by attaching targeting moiety, folate and with encapsulation of a potent anticancerous drug, 5FU. We have conjugated an imaging moiety along with nanocomposite to study the effective uptake of nanoparticles. It was also observed that the dye labeled folate targeted nanoparticles could effectively enter into cancer cells and the fate of nanoparticles was tracked with Lysotracker. The biocompatibility of EPS coated MNPs and synergistic effect of magnetic hyperthermia and drug for enhanced antiproliferation of cancer cells was also evaluated. More than 80% of cancer cells was killed within a period of 60 min when magnetic hyperthermia (MHT) was applied along with drug loaded EPS coated MNPs, thus signifying the combined effect of drug loaded MNPs and MHT. Our results suggests that MR and GG coated MNPs exhibited excellent biocompatibility with low cell cytotoxicity, high therapeutic potential, and superparamagnetic behavior that can be employed as prospective candidates for bacterial EPS based targeted drug delivery, cancer cell imaging and for MHT for killing cancer cells within short period of time.

  9. Effects of ELF magnetic fields on protein expression profile of human breast cancer cell MCF7

    Institute of Scientific and Technical Information of China (English)

    LI Han; ZENG Qunli; WENG Yu; LU Deqiang; JIANG Huai; XU Zhengping

    2005-01-01

    Extremely Low Frequency Magnetic Fields (ELF MF) has been considered as a "possible human carcinogen" by International Agency for Research on Cancer (IARC) while credible mechanisms of its carcinogenicity remain unknown. In this study, a proteomics approach was employed to investigate the changes of protein expression profile induced by ELF MF in human breast cancer cell line MCF7, in order to determine ELF MF-responsive proteins. MCF7 cells were exposed to 50 Hz, 0.4 mT ELF MF for 24 h and the changes of protein profile were examined using two dimensional electrophoresis. Up to 6 spots have been statistically significantly altered (their expression levels were changed at least 5 fold up or down) compared with sham-exposed group. 19 ones were only detected in exposure group while 19 ones were missing. Three proteins were identified by LC-IT Tandem MS as RNA binding protein regulatory subunit、Proteasome subunit beta type 7 precursor and Translationally Controlled Tumor Protein. Our finding showed that 50 Hz, 0.4 mT ELF MF alternates the protein profile of MCF7 cell and may affect many physiological functions of normal cell and 2-DE coupled with MS is a promising approach to elucidating cellular effects of electromagnetic fields.

  10. The prophylactic effect of probiotic Enterococcus lactis IW5 against different human cancer cells

    Directory of Open Access Journals (Sweden)

    YOUSEF eNAMI

    2015-11-01

    Full Text Available Enterococcus lactis IW5 was obtained from human gut and the potential probiotic characteristics of this organism were then evaluated. Results showed that this strain was highly resistant to low pH and high bile salt and adhered strongly to Caco-2 human epithelial colorectal cell lines. The supernatant of E. lactis IW5 strongly inhibited the growth of several pathogenic bacteria and decreased the viability of different cancer cells, such as HeLa, AGS, HT-29, and MCF-7. Conversely, E. lactis IW5 did not inhibit the viability of normal FHs-74 cells. This strain did not generate toxic enzymes, including β-glucosidase, β-glucuronidase, and N-acetyl-β-glucosaminidase and was highly susceptible to ampicillin, gentamycin, penicillin, vancomycin, clindamycin, sulfamethoxazol, and chloramphenicol but resistant to erythromycin and tetracyclin. This study provided evidence for the effect of E. lactis IW5 on cancer cells. Therefore, E. lactis IW5, as a bioactive therapeutics, should be subjected to other relevant tests to verify the therapeutic suitability of this strain for clinical applications.

  11. Apoptotic effects of cooked and in vitro digested soy on human prostate cancer cells.

    Science.gov (United States)

    Dong, Xin; Xu, Wenqing; Sikes, Robert A; Wu, Changqing

    2012-12-01

    Previous laboratory and animal studies reported that soy isoflavones were major bioactive compounds in soy to exert chemoprotection of prostate cancer. However, these studies cannot reflect the realistic effects that soy may induce through diets, and little is known about the bioavailability of isoflavones from whole soy food and their bioactivities after cooking and digestion. In this study, cooking and in vitro digestion were used to prepare soy extracts and the effects of cooking and digestion on the isoflavone contents and bioactivities of the whole soy extracts were examined. The cooking procedure generally increased the amount of daidzin, genistin and daidzein, but decreased that of genistein. Digestion process significantly lowered contents of daidzin and genistin in 60min cooked sample, while increased the contents of daidzin and daidzein and decreased the content of genistein in the uncooked sample. Antioxidant activities of soy extracts increased after cooking and in vitro digestion, while no consistent increase of the four soy isoflavones was determined. The apoptotic effects of soy extracts on both LNCaP and C4-2B cells were generally in a dose-dependent manner. Compared to purified single isoflavones, cooked and digested soy were more effective on induction of prostate cancer cell apoptosis, which indicated synergistic interactions between various bioactive compounds in the whole soy.

  12. Inhibitory effect of Polo-like kinase 1 depletion on mitosis and apoptosis of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xue-Hua Chen; Bin Lan; Ying Qu; Xiao-Qing Zhang; Qu Cai; Bing-Ya Liu; Zheng-Gang Zhu

    2006-01-01

    AIM: Polo-like kinase 1 (PLK1) serine/threonine kinase plays a vital role in multiple phases of mitosis in gastric cancer cells. To investigate the effect of PLK1 depletion on mitosis and apoptosis of gastric cancer cells.METHODS: PLK1 expression was blocked by small RNA interference(siRNA). The expression levels of PLK1, cdc2, cyclin B and caspase 3 were detected by Western blotting. Then, PLK1 depletion, cdc2 activity,cell proliferation, cell cycle phase distribution, mitotic spindle structure, and the rate of apoptosis of the PLK1knockdown cells were observed.RESULTS: PLK1 gene knockdown was associated with increased cyclin B expression, increased cdc2 activity (but not with the expression levels), accumulation of gastric cancer cells at G2/M, improper mitotic spindle formation,delayed chromosome separation and delayed or arrested cytokinesis. Moreover, PLK1 depletion in gastric cancer cells was associated with decreased proliferation,attenuated pro-caspase 3 levels and increased apoptosis.CONCLUSION: Blockage of PLK1 expression may lead to decreased mitosis or even apoptosis in gastric cancer cells, indicating that PLK1 may be a valuable therapeutic target for gastric cancer.

  13. Cancer stem cell theory and the warburg effect, two sides of the same coin?

    Science.gov (United States)

    Pacini, Nicola; Borziani, Fabio

    2014-05-19

    Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific "metabolic sign" has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific "metabolic sign" reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

  14. Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

    Directory of Open Access Journals (Sweden)

    Nicola Pacini

    2014-05-01

    Full Text Available Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

  15. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska

    2013-08-01

    Full Text Available Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  16. Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李占东; 高非; 张莹; 孙红; 李萍萍

    2009-01-01

    Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs...

  17. Cytotoxic, genotoxic and apoptotic effects of naringenin-oxime relative to naringenin on normal and cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Abdurrahim Kocyigit; Ismail Koyuncu; Murat Dikilitas; Fatemeh Bahadori; Baki Turkkan

    2016-01-01

    Objective: To assess and compare the cytotoxic, genotoxic, apoptotic and reactive oxygen species (ROS) generating effects of naringenin (NG) and its new derived compound naringenin-oxime (NG-Ox) on MCF-7, HT-29, PC-12 cancer and L-929 normal cell lines. Methods: The cells were incubated with different doses of NG-Ox and NG (50–1 000 mmol/L) for 24 h. The cell viability was assessed based on ATP cell viability assay. Intracellular accumulation of ROS was determined using the fluorescent probes 2070-dichlorodihydrofluorescin diacetate. Genotoxic effects were evaluated by alkaline single cell gel electrophoresis assay (comet assay) and, the apoptotic effect was evaluated by acridine orange staining at below the IC50 levels. Results: Both NG-Ox and NG exhibited cytotoxic, genotoxic and apoptotic effects and resulted in increased ROS values in a dose-dependent manner. The effects were more pronounced on cancer cell lines. The cytotoxic, genotoxic and apoptotic effects of NG-Ox were higher than that of NG in all cell lines. Significant correlations were observed be-tween cell viability, DNA damage, apoptosis and ROS, in all cell lines exposed to either NG-Ox or NG. Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.

  18. Cancer stem cells in human gastrointestinal cancer.

    Science.gov (United States)

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  19. Effect of Helicobacter pylori VacA on gene expression of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Wang; Zhen-Hong Li; Jian-Ping Yuan; Wei Zhao; Xiao-Dong Shi; Shan-Qing Tong; Xiao-Kui Guo

    2005-01-01

    AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells.METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA+ and VacA- Hpylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy.RESULTS: A total of 16 000 cDNA clones were detected.The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA+ BCS reached 5%,compared with that challenged by Vac A- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels.Host of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton,apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA+ BCS showed collapsed and disrupted microtubular cytoarchitecture.CONCLUSION: VacA+ BCS can disrupt cytoskeletal architecture,likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors.VacA+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.

  20. The Apoptotic Effects of the P300 Activator on Breast Cancer and Lung Fibroblast Cell Lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Salahshoor

    2013-10-01

    Full Text Available Background: P300 is an enzyme that acetylates histones during stress. It alsoacetylates several non-histone proteins, including P53 which is the most important tumorsuppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby,this study describes the potency of cholera toxin B subunit as a P300 activator to induceapoptosis in a breast cancer cell line (MCF-7 and a lung fibroblast cell line (MRC-5as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with orwithout cholera toxin B subunit at the concentration of 85.43 μmol/L, based on the half-maximal inhibitory concentration index at different times (24, 48 and 72 h. Thepercentage of apoptotic cells was measured by flow cytometry. Real-time quantitativeRT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with cholera toxin B subunit at different times. We used the ELISA and Bradford proteintechniques to detect levels of total and acetylated P53 protein generated in MCF-7 andMRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively andsignificantly induced more apoptosis in MCF-7 compared to MRC-5. We showed thatexpression of P300 up-regulated by increasing the time of the cholera toxin B subunittreatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53protein levels increased more in MCF-7 cells than in MRC-5 cells.Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, butit could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can besuggested as an anti-cancer agent.

  1. Cytotoxic and apoptogenic effects of Strobilanthes crispa Blume extracts on nasopharyngeal cancer cells.

    Science.gov (United States)

    Koh, Rhun Yian; Sim, Yi Chi; Toh, Hwee Jin; Liam, Liang Kuan; Ong, Rachael Sze Lynn; Yew, Mei Yeng; Tiong, Yee Lian; Ling, Anna Pick Kiong; Chye, Soi Moi; Ng, Khuen Yen

    2015-10-01

    The chemotherapeutic agents used to treat nasopharyngeal cancer (NPC) exhibit low efficacy. Strobilanthes crispa Blume is widely used for its anticancer, diuretic and anti‑diabetic properties. The present study aimed to determine the cytotoxic and apoptogenic effects of S. crispa on CNE‑1 NPC cells. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5 diphenyl tetrazolium bromide assay was used to evaluate the cytotoxic effects of S. crispa against CNE‑1 cells. The rate of apoptosis was determined using propidium iodide staining and caspase assays. Ethyl acetate, hexane and chloroform extracts of S. crispa leaves all exhibited cytotoxic effects on CNE‑1 cells, at a half maximal inhibitory concentration (IC50) of 119, 123.5 and 161.7 µg/ml, respectively. In addition, hexane, chloroform and ethyl acetate extracts of S. crispa stems inhibited CNE‑1 cell proliferation, at a IC50 of 49.4, 148.3 and 163.5 µg/ml, respectively. Flow cytometric analysis revealed an increased proportion of cells in the sub G1 phase and a decreased proportion of cells in the G2/M phase, following treatment with the extracts. However, the extracts did not alter the activities of caspase ‑3/7, ‑8 and ‑9. No cytotoxic effect was observed when the cells were treated with the methanol and water extracts of S. crispa stems and leaves. In conclusion, the S. crispa extracts were cytotoxic against CNE‑1 cells and these extracts were able to induce apoptosis, independent of caspase activation.

  2. Antitumor Effects of Saffron-Derived Carotenoids in Prostate Cancer Cell Models

    Directory of Open Access Journals (Sweden)

    Claudio Festuccia

    2014-01-01

    Full Text Available Crocus sativus L. extracts (saffron are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE and crocin (CR exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT, and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1 which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

  3. Effect of pseudolaric acid B on gastric cancer cells: Inhibition of proliferation and induction of apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ke-Shen Li; Xue-Feng Gu; Ping Li; Yong Zhang; Ya-Shuang Zhao; Zhen-Jiang Yao; Nai-Qiang Qu; Bin-You Wang

    2005-01-01

    AIM: To examine the effect of pseudolaric acid B on the growth of human gastric cancer cell line, AGS, and its possible mechanism of action.METHODS: Growth inhibition by pseudolaric acid B was analyzed using MTT assay. Apoptotic cells were detected using Hoechst 33258 staining, and confirmed by DNA fragmentation analysis. Western blot was used to detect the expression of apoptosis-regulated gene Bcl-2, caspase 3, and cleavage of poly (ADP-ribose)polymerase-1 (PARP-1).RESULTS: Pseudolaric acid B inhibited the growth of AGS cells in a time- and dose-dependent manner by arresting the cells at G2/M phase, which was accompanied with a decrease in the levels of cdc2.AGS cells treated with pseudolaric acid B showed typical characteristics of apoptosis including chromatin condensation and DNA fragmentation. Moreover,treatment of AGS cells with pseudolaric acid B was also associated with decreased levels of the anti-apoptotic protein Bcl-2, activation of caspase-3, and proteolytic cleavage of PARP-1.CONCLUSION: Pseudolaric acid B can dramatically suppress the AGS cell growth by inducing apoptosis after G2/M phase arrest. These findings are consistent with the possibility that G2/M phase arrest is mediated by the down-regulation of cdc2 levels. The data also suggest that pseudolaric acid B can trigger apoptosis by decreasing Bcl-2 levels and activating caspase-3 protease.

  4. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells

    Science.gov (United States)

    Liu, P; Brown, S; Goktug, T; Channathodiyil, P; Kannappan, V; Hugnot, J-P; Guichet, P-O; Bian, X; Armesilla, A L; Darling, J L; Wang, W

    2012-01-01

    Background: Glioblastoma multiforme (GBM) cells are resistant to anticancer drugs. Cancer stem cells (CSCs) are a key mediator of chemoresistance. We have reported that disulfiram (DS), an aldehyde dehydrogenase (ALDH) inhibitor, targets breast CSC-like cells. In this study, the effect of DS and combination of DS and gemcitabine (dFdC) on GBM cells and GBM stem-like cells was investigated. Methods: 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)-isobologram, western blot, luciferase reporter gene assay, electrophoretic mobility-shift assay and ALDH analysis were used in this study. Results: Disulfiram is cytotoxic in GBM cell lines in a copper (Cu)-dependent manner. Disulfiram/copper enhances the cytotoxicity of dFdC. Combination index-isobologram analysis indicates a synergistic effect between DS/Cu and dFdC. Disulfiram/copper induces reactive oxygen species (ROS), activates JNK and p38 pathways and inhibits nuclear factor-kappa B activity in GBM cell lines. Disulfiram/copper may trigger intrinsic apoptotic pathway via modulation of the Bcl2 family. Disulfiram/copper abolishes stem-like cell population in GBM cell lines. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu and the enhancing effect of DS/Cu on the cytotoxicity of dFdC in GBM stem-like cells may be caused by induction of ROS and inhibition of both ALDH and the NFkB pathway. Both DS and dFdC can traverse the blood–brain barrier. Further study may lead them into GBM chemotherapy. PMID:23033007

  5. NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation.

    Science.gov (United States)

    Yoshinaga, Ayana; Kajiya, Natsuki; Oishi, Kazuki; Kamada, Yuko; Ikeda, Asami; Chigwechokha, Petros Kingstone; Kibe, Toshiro; Kishida, Michiko; Kishida, Shosei; Komatsu, Masaharu; Shiozaki, Kazuhiro

    2016-07-05

    Naringin, which is one of the flavonoids contained in citrus fruits, is well known to possess various healthy functions to humans. It has been reported that naringin suppresses cancer cell growth in vitro and in vivo, although the underlying mechanisms are not fully understood. Recently, the roles of glycoconjugates, such as gangliosides, in cancer cells have been focused because of their regulatory effects of malignant phenotypes. Here, to clarify the roles of naringin in the negative-regulation of cancer cell growth, the alteration of glycoconjugates induced by naringin exposure and its significance on cell signaling were investigated. Human cancer cells, HeLa and A549, were exposed to various concentrations of naringin. Naringin treatment induced the suppression of cell growth toward HeLa and A549 cells accompanied with an increase of apoptotic cells. In naringin-exposed cells, GM3 ganglioside was drastically increased compared to the GM3 content prior to the treatment. Furthermore, naringin inhibited NEU3 sialidase, a GM3 degrading glycosidase. Similarly, NEU3 inhibition activities were also detected by other flavanone, such as hesperidin and neohesperidin dihydrocalcone, but their aglycones showed less inhibitions. Naringin-treated cancer cells showed suppressed EGFR and ERK phosphorylation levels. These results suggest a novel mechanism of naringin in the suppression of cancer cell growth through the alteration of glycolipids. NEU3 inhibitory effect of naringin induced GM3 accumulation in HeLa and A549 cells, leading the attenuation of EGFR/ERK signaling accompanied with a decrease in cell growth.

  6. Analysis of resveratrol and radiation effects in lung cancer cells by micronucleus assay

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina S.; Santos, Dymes R.A.; Vieira, Daniel P.; Rogero, Sizue O.; Rogero, Jose R., E-mail: carolina_sm@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Sakuraba, Roberto K.; Weltman, Eduardo [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Cruz, Aurea S.; Santos, Rezolina P. [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2015-07-01

    Mucoepidermoid lung carcinoma is frequently manifested by obstructive trachea symptoms. Radiation and drugs combinations are commonly used in the lung cancer treatment. Currently there is a strong tendency to develop therapeutic strategies focused at the administration of high potential compounds to improve the ionizing radiation treatments, so as to increase the radiation effects on tumor cell while minimizing these effects to surrounding normal tissues. Resveratrol is a polyphenolic phytoalexin compound present in wines and several plants. This compound has a broad spectrum of biological activities such as antioxidant, anticarcinogenic, and induction of cell cycle arrest effects. Analysis of biological effects of ionizing radiation in the presence of resveratrol in different cell cultures has been the subject of many studies. To verify the genotoxic effects in cells exposed to ionizing radiation many methods have been proposed. The cytokinesis-block micronucleus technique is one of the preferred methods. The main of this study was to detect and quantify radioinduced DNA damage in mucoepidermoid lung carcinoma cells (NCI-H292) by cytokinesis-block micronucleus technique using cytocalasin-B. The cell culture was irradiated at a single fraction from a TrueBeam® linear accelerator (0, 0.8, 5, and 10 Gy), in the absence or presence of different resveratrol concentrations (0, 15, 30, and 60 μM). The results showed that resveratrol (15 and μM) induced significant increase frequency (p<0.05) of micronucleus formation in NCI-H292 cell culture non-irradiated and exposed at 5 Gy dose. Moreover, resveratrol (30 μM) induced micronucleus formation at 0.8 Gy dose. (author)

  7. Growth-inhibitory Effects of Curcumin on Ovary Cancer Cells and Its Mechanisms

    Institute of Scientific and Technical Information of China (English)

    郑丽端; 童强松; 吴翠环

    2004-01-01

    Summary: To study the growth-inhibitory ettects ot curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 μmol/L-50 μmol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl-2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41% -28.48% (P<0.01). The expression of bcl-2 and p53 was decreased, which depended on the action time (P<0.01). There were no obvious changes in MDM2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of its molecular mechanisms.

  8. Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose on human esophageal cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Hong Lu; Yun Zhou; Liang Qiao; Rui Ji; Ai-Qing Wang; Wei-Min Liu; Qun-Ji Xue

    2004-01-01

    AIM: To determine whether 2-(3-carboxy-1-oxopropy1)amino-2-deoxy-D-glucose (COPADG), a derivative of Damino-glucose, inhibited the growth of human esophageal cancer cell line Eca-109.METHODS: Effects of COPADG on Eca-109 cells cultured in RPMI 1640 medium were examined by a tetrazoliumbased colorimetric assay (MTT assay).RESULTS: COPADG inhibited the growth of Eca-109 cells in a dose- and time-dependent manner; the maximum inhibition rate was 83.75%.CONCLUSION: COPADG can directly inhibit the proliferation of Eca-109 cells, which may serve as the experimental evidence for development of new drugs for esophageal cancer therapy.

  9. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jie Xiao

    2016-09-01

    Full Text Available The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC, we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  10. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  11. The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells In vitro.

    Science.gov (United States)

    Brown, Amy C; Reitzenstein, Jonathan E; Liu, Jessie; Jadus, Martin R

    2005-09-01

    Hawaiians tend to have lower incidence rates of colorectal cancer and it was hypothesized that this may be due to ethnic differences in diet, specifically, their consumption of poi, a starchy paste made from the taro (Colocasia esulenta L.) plant corm. Soluble extracts of poi were incubated at 100 mg/mL in vitro for antiproliferative activity against the rat YYT colon cancer cell line. (3)H-thymidine incorporation studies were conducted to demonstrate that the poi inhibited the proliferation of these cancer cells in a dose-dependent manner. The greatest suppression of YYT colon cancer growth occurred when 25% concentration was used. When poi was incubated with the YYT cells after 2 days, the YYT cells underwent apoptotic changes as evidenced by a positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Poi enhanced the proliferation of normal mouse splenocyte control cells, suggesting that poi is not simply toxic to all cells but even has a positive immunostimulatory role. By flow cytometry, T cells (CD4+ and CD8+) were predominantly activated by the poi. Although numerous factors can contribute to the risk of colon cancer, perhaps poi consumption may contribute to the lower colon cancer rates among Hawaiians by two distinct mechanisms. First, by inducing apoptosis within colon cancer cells; second, by non-specifically activating lymphocytes, which in turn can lyse cancerous cells. Our results suggest for the first time that poi may have novel tumor specific anti-cancer activities and future research is suggested with animal studies and human clinical trials.

  12. Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol(®)-resistant ovarian cancer.

    Science.gov (United States)

    Shen, Yao-An; Li, Wai-Hou; Chen, Po-Hung; He, Chun-Lin; Chang, Yen-Hou; Chuang, Chi-Mu

    2015-01-01

    Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

  13. Inhibitory effects of small molecular peptides from Spirulina (Arthrospira) platensis on cancer cell growth.

    Science.gov (United States)

    Wang, Zhujun; Zhang, Xuewu

    2016-02-01

    In this study, the whole proteins of Spirulina (Arthrospira) platensis were extracted, hydrolysis with three proteases (trypsin, alcalase and papain) was performed, and gel filtration chromatography was employed to separate hydrolysates. Totally, 15 polypeptides were isolated, which showed anti-proliferation activities on five cancer cells (HepG-2, MCF-7, SGC-7901, A549 and HT-29), with the IC50 values between <31.25 and 336.57 μg mL(-1). Moreover, a new peptide YGFVMPRSGLWFR was identified from papain-digested hydrolysates. It also exhibited inhibitory activities on cancer cells, and the best activity was observed on A549 cancer cells (IC50 values 104.05 μg mL(-1)). In other words, these polypeptides exhibited anti-proliferation activities on cancer cells, and low toxicity or stimulatory activity on normal cells, suggesting that they are promising ingredients in food and pharmaceutical applications.

  14. The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression.

    Science.gov (United States)

    Ho, Nelson; Morrison, Jodi; Silva, Andreza; Coomber, Brenda L

    2016-01-06

    Cancer cells heavily rely on the glycolytic pathway regardless of oxygen tension. Hexokinase II (HKII) catalyses the first irreversible step of glycolysis and is often overexpressed in cancer cells. 3-Bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of altering critical metabolic pathways in cancer cells. Abnormal vasculature within tumours leads to heterogeneous microenvironments, including glucose availability, which may affect drug sensitivity. The aim of the present study was to elucidate the mechanisms by which 3BP acts on colorectal cancer (CRC) cells with focus on the HKII/Akt signalling axis. High HKII-expressing cell lines were more sensitive to 3BP than low HKII-expressing cells. 3BP-induced rapid Akt phosphorylation at site Thr-308 and cell death via both apoptotic and necrotic mechanisms. Cells grown under lower glucose concentrations showed greater resistance towards 3BP. Cells with HKII knockdown showed no changes in 3BP sensitivity, suggesting the effects of 3BP are independent of HKII expression. These results emphasize the importance of the tumour microenvironment and glucose availability when considering therapeutic approaches involving metabolic modulation.

  15. Targeting stemness is an effective strategy to control EML4-ALK+ non-small cell lung cancer cells.

    Science.gov (United States)

    Oh, Se Jin; Noh, Kyung Hee; Lee, Young-Ho; Hong, Soon-Oh; Song, Kwon-Ho; Lee, Hyo-Jung; Kim, Soyeon; Kim, Tae Min; Jeon, Ju-Hong; Seo, Jae Hong; Kim, Dong-Wan; Kim, Tae Woo

    2015-11-24

    The fusion between anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) is a causative factor in a unique subset of patients with non-small cell lung carcinoma (NSCLC). Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS. Cancer stem cell (CSC) theory provides a plausible explanation for acquisition of tumorigenesis and resistance. However, the question as to whether EML4-ALK-driven tumorigenesis is linked with the stem-like property and whether the stemness is an effective target in controlling EML4-ALK+ NSCLC including crizotinib-resistant NSCLC cells has not been addressed. Here, we report that stem-like properties stem from ALK activity in EML4-ALK+ NSCLC cells. Notably, treatment with rapamycin, a CSC targeting agent, attenuates stem-like phenotypes of the EML4-ALK+ cells, which increased capability of tumor formation and higher expression of stemness-associated molecules such as ALDH, NANOG, and OCT4. Importantly, combinational treatment with rapamycin and crizotinib leads to synergistic anti-tumor effects on EML4-ALK+ NSCLC cells as well as on those resistant to crizotinib. Thus, we provide a proof of principle that targeting stemness would be a novel strategy to control intractable EML4-ALK+ NSCLC.

  16. Presence of CCK-A, B receptors and effect of gastrin and cholecystokinin on growth of pancreatobiliary cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Jin-Young Jang; Sun-Whe Kim; Ja-Lok Ku; Yong-Hyun Park; Jae-Gahb Park

    2005-01-01

    AIM: To investigate the effects of gastrin and cholecystokinin (CCK) and their specific antagonists on the growth of pancreatic and biliary tract cancer cell lines.METHODS: Five pancreatic and 6 biliary cancer cell lines with 2 conrtol cells were used in this study. Cell proliferation study was done using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test and direct cell count method. Reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization were performed to examine and quantify the expression of hormonal receptors in these cell lines.RESULTS: SNU-308 showed a growth stimulating effect by gastrin-17, as did SNU-478 by both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260for gastrin and L-364, 718 for CCK). Other cell lines did not respond to gastrin or CCK. In RT-PCR, the presence of CCK-A receptor and CCK-B/gastrin receptor mRNA was detected in all biliary and pancreatic cancer cell lines. In slot blot hybridization, compared to the cell lines which did not respond to hormones, those that responded to hormones showed high expression of receptor mRNA.CONCLUSION: Gastrin and CCK exert a trophic action on some of the biliary tract cancers.

  17. Co-cultivation of pancreatic cancer cells with orthotopic tumor-derived fibroblasts: fibroblasts stimulate tumor cell invasion via HGF secretion whereas cancer cells exert a minor regulative effect on fibroblasts HGF production.

    Science.gov (United States)

    Qian, Li-Wu; Mizumoto, Kazuhiro; Maehara, Naoki; Ohuchida, Kenoki; Inadome, Naoki; Saimura, Michiyo; Nagai, Eishi; Matsumoto, Kunio; Nakamura, Toshikazu; Tanaka, Masao

    2003-02-10

    The intensive stromal reaction is one of characteristics of pancreatic exocrine carcinoma. The mutual interaction between pancreatic cancer cells and orthotopic tumor-derived fibroblasts have not been clarified yet. In this study, we sought to elucidate the mechanism underlying the tumor-stromal interaction with an in vitro coculture experimental system. Considerable strong c-Met expression was detected in seven out ten lines of human pancreatic carcinoma cells, as determined by Western blotting. For hepatocyte growth factor (HGF)-production, however, none or only trace amounts of HGF could be detected in those ten cell lines. Of the two lots of tumor-derived fibroblasts obtained from two pancreatic cancer patients, the fibroblasts capable to produce HGF could initiate an apparent invasion-stimulating response in strong c-Met-expressed Suit-2 and Panc-1 cells but not in faint expressed Mia PaCa-2 and BxPC-3 cells. A specialized HGF antagonist, NK4 would effectively inhibit the fibroblast-mediated invasive growth, thus proving the key role of the paracrine-fashioned HGF/c-Met pathway in the tumor-stromal interaction. On the other hand, the regulative action of cancer cells on HGF expression of fibroblasts was also investigated using direct or indirect coculture systems. For the fibroblasts that originally did not produce HGF, cancer cells failed to show any HGF-inductive effect. For the HGF-producing fibroblasts, despite of somewhat upregulation or downregulation in fibroblast HGF expression, the feedback regulation by studied pancreatic cancer cells in both coculture modes were relatively limited. This in vitro study sketched out the interaction between cancerous and stromal compartments with an emphasis on HGF/c-Met signal pathway, thus possibly helping to unveil the more complicated mutual modulation in vivo between pancreatic cancer and host mesenchymal tissues.

  18. Inhibitive effect of 3-bromopyruvic acid on human breast cancer MCF-7 cells involves cell cycle arrest and apoptotic induction

    Institute of Scientific and Technical Information of China (English)

    LIU Xiao-hong; ZHENG Xue-fang; WANG Yong-li

    2009-01-01

    Background Breast cancer is one of the most common malignancies in women and is highly resistant to chemotherapy. Due to its high tumour selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism has been proposed as a specific anticancer agent. The present study determined the effect of 3-BrPA on proliferation, cell cycle and apoptosis in the human breast cancer MCF-7 cell line and other antitumour mechanisms. Methods MCF-7 cells were treated with various concentrations of 3-BrPA for 1-4 days, and cell growth was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. Marked morphological changes in MCF-7 cells after treatment with 3-BrPA were observed using transmission electron microscopy. The distributions of the cell cycle and apoptosis were analyzed by flow cytometry. Immunohistochemistry was used to indicate the changes in the expression of Bcl-2, c-Myc, and mutant p53. Results 3-BrPA (25 μg/ml) significantly inhibited the proliferation of MCF-7 cells in a time-dependent manner. The MCF-7 cells exposed to 3-BrPA showed the typical morphological characteristics of apoptosis, including karyopycnosis, nuclear condensation and oversize cytoplasmic particles. In addition, flow cytometric assay also showed more apoptotic cells after 3-BrPA stimulation. The cells at the GO and G1 phases were dramatically decreased while cells at the S and G2/M phases were increased in response to 3-BrPA treatment after 48 hours. Furthermore, 3-BrPA stimulation decreased the expressions of Bcl-2, c-Myc and mutant p53, which were strongly associated with the programmed cell death signal transduction pathway. Conclusion 3-BrPA inhibits proliferation, induces S phase and G2/M phase arrest, and promotes apoptosis in MCF-7 cells, which processes might be mediated by the downregulation of the expressions of Bcl-2, c-Myc and mutant p53.

  19. Effects of 5-FU combined compound Ginseng and Astragalus on biological behavior of human gastric cancer MGC-803 cells

    Institute of Scientific and Technical Information of China (English)

    韦尉元

    2013-01-01

    Objective To observe the in vitro effects of 5-fluorouracil(5-FU) combined Compound Ginseng and Astragalus(CGA) on the biological behaviors such as the proliferation,the cloning,apoptosis and migration of human gastric cancer MGC-803 cells. Methods The cell proliferation inhibition rate was detected by MTT assay,

  20. Chemopreventive Effects of Peucedanum praeruptorum DUNN and Its Major Constituents on SGC7901 Gastric Cancer Cells

    Directory of Open Access Journals (Sweden)

    Qingshan Li

    2010-11-01

    Full Text Available In this study, the effects of Peucedanum praeruptorum DUNN methanolic extract (PPME and its major constituents on SGC7901 human gastric cancer cells were evaluated. Two pyranocoumarins, namely, (± praeruptorin A (PA and (± praeruptorin B (PB, were isolated from PPME. A high performance liquid chromatographic (HPLC method was developed to determine the contents of PA and PB in PPME. The antiproliferative and cytotoxic actions of PPME were observed using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and release of lactate dehydrogenase (LDH assays. At 300 µg/mL, PPME inhibited cell growth by 51.2% (P < 0.01, probably linked to the high concentration of PA and PB. Both PA and PB exhibited antiproliferative and cytotoxic activities on the SGC7901 cells. Furthermore, the active principle compound, PA, also enhanced the actions of doxorubincin (DOX on SGC7901 cells. Cell growth decreased higher with the combined treatment of PA and DOX than that with the chemotherapy agent applied alone, suggesting that PA could reduce the dose of DOX for the desired effects.

  1. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Energy Technology Data Exchange (ETDEWEB)

    Uma Suganya, K.S. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Govindaraju, K., E-mail: govindtu@gmail.com [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Ganesh Kumar, V. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Prabhu, D.; Arulvasu, C. [Department of Zoology, University of Madras, Guindy campus, Chennai 600 025 (India); Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India)

    2016-05-15

    Highlights: • Biosynthesis of stable and well dispersed predominantly spherical gold nanoparticles of size around ∼12.5 nm. • Anticancer assessment of gold nanoparticles on MDA-MB-231 and MCF-7 cell lines. • AuNPs were found non toxic to normal HMEC cells. • Flow cytometry results revealed significant arrest in cell proliferation in early G0/G1 to S phase. - Abstract: Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G{sub 0}/G{sub 1} to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  2. Preliminary investigations of Spirulina effect on cancer cells: interest for long-term manned space missions

    Science.gov (United States)

    Baatout, S.; Bekaert, S.; Hendrickx, L.; Derradji, H.; Mergeay, M.

    Background In view of long haul space exploration missions the development of regenerative life support systems is of crucial importance to increase the crew autonomy and decrease the cost associated to the mass embarked Therefore in the late 80 s the European Space Agency initiated the MELiSSA project Micro-Ecological Life Support System Alternative MELiSSA has been conceived as a micro-organisms and higher plant process enabling high recycling efficiency The cyanobacteria Arthrospira sp is occupying one of the MELiSSA compartments Its genome is now being sequenced and this will help to better understand or improve its food value as well as to have a look at its putative toxic potential Aim In this study we were interested in studying the threshold of intrinsic cytotoxic effects of Spirulina dry extract from Sigma containing washed and lyophilized mixed Arthrospira strains on human cancer cells and its cell type dependency Method For that purpose we used flow cytometry to estimate cell death apoptosis and necrosis in three human leukaemic cell lines HELA cervix carcinoma IM-9 multiple myeloma K562 chronic myelogenous leukaemia Cells were cultured in the presence of an aqueous extract of Spirulina concentrations ranging from 0 to 500 mu g ml for 15 to 40 hours Apoptosis and necrosis were evaluated by annexin-V-PI staining cell size and granularity Early apoptosis was monitored by analysing the maintenance of mitochondrial membrane potential DioC 6 3 and the

  3. Cadmium effects on p38/MAPK isoforms in MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Casano, Caterina; Agnello, Maria; Sirchia, Rosalia; Luparello, Claudio

    2010-02-01

    Emerging evidence seems to indicate that the heavy metal cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in normal and pathological eukaryotic cells, also affecting intracellular signalization events. Human p38 is a family of mitogen-activated protein kinases consisting of four isoforms (alpha, beta, gamma and delta) which mediate signal transduction cascades controlling several aspects of cell physiology. In this study we examined whether exposure of MDA-MB231 tumor cells from the human breast to Cd may exert some effect on p38 isoform expression and accumulation, as well as on p38 activation. Employing a combination of proliferation tests, conventional and semiquantitative multiplex (SM)-polymerase chain reaction (PCR) and Western blot assays, we report that the treatment of breast cancer cells with 5 microM CdCl(2) induces a diversified modulation of the transcription patterns of p38 isoform genes and of the accumulation of the related protein products, which are, on the other hand, also affected by alpha and beta isoform functional inactivation induced by SB203580. Our findings suggest the existence of so far unexplored mechanisms of gene regulation in our model system and validate that MDA-MB231 cell line is a suitable in vitro model for further and more detailed studies on the intracellular mechanisms underlying the control of p38 expression, synthesis and activation in mammary tumor cells exposed to different stresses.

  4. Probiotic potential and biotherapeutic effects of newly isolated vaginal Lactobacillus acidophilus 36YL strain on cancer cells.

    Science.gov (United States)

    Nami, Yousef; Abdullah, Norhafizah; Haghshenas, Babak; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari

    2014-08-01

    Lactobacillus acidophilus is categorized as a probiotic strain because of its beneficial effects in human health and prevention of disease transmission. This study is aimed to characterize the probiotic potential of L. acidophilus 36YL originally isolated from the vagina of healthy and fertile Iranian women. The L. acidophilus 36YL strain was identified using 16S rDNA gene sequencing and characterized by biochemical methodologies, such as antibiotics susceptibility, antimicrobial activity, and acid and bile resistance. The bioactivity of the secretion of this strain on four human cancer cell lines (AGS, HeLa, MCF-7, and HT-29) and one normal cell line (HUVEC) was evaluated by cytotoxicity assay and apoptosis analysis. This newly isolated strain was found to exhibit notable probiotic properties, such as admirable antibiotic susceptibility, good antimicrobial activity, and favorable resistance to acid and bile salt. The results of bioactivity assessment demonstrated acceptable anticancer effects on the four tested cancer cell lines and negligible side effects on the assayed normal cell line. Our findings revealed that the anticancer effect of L. acidophilus 36YL strain secretions depends on the induction of apoptosis in cancer cells. L. acidophilus 36YL strain is considered as a nutraceutical alternative or a topical medication with a potential therapeutic index because of the absence of cytotoxicity to normal cells, but effective toxicity to cancer cell lines.

  5. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  6. Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

    Directory of Open Access Journals (Sweden)

    Sachiko Hirai

    Full Text Available Up-regulated sirtuin 1 (SIRT1, an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53. Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5. In the KatoIII cell line (TP53-null, DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.

  7. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549

    Science.gov (United States)

    Lee, W. D.; Liang, Y. J.; Chen, B. H.

    2016-12-01

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  8. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy.

    Science.gov (United States)

    Zhang, Xi-Feng; Gurunathan, Sangiliyandi

    2016-01-01

    Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs) using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16-20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal) is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC)-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL), which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination treatment increased the therapeutic potential and demonstrated the relevant targeted therapy for the treatment of ovarian cancer. Furthermore, we provide, for the first time, a mode of action for Sal and AgNPs in ovarian cancer cells: enhanced apoptosis and autophagy.

  9. THE CYTOTOXIC EFFECTS OF LOW INTENSITY VISIBLE AND INFRARED LIGHT ON HUMAN BREAST CANCER (MCF7 CELLS

    Directory of Open Access Journals (Sweden)

    P Peidaee

    2013-03-01

    Full Text Available A concept of using low intensity light therapy (LILT as an alternative approach to cancer treatment is at early stages of development; while the therapeutic effects of LILT as a non-invasive treatment modality for localized joint and soft tissue wound healing are widely corroborated. The LEDs-based exposure system was designed and constructed to irradiate the selected cancer and normal cells and evaluate the biological effects induced by light exposures in visible and infrared light range. In this study, human breast cancer (MCF7 cells and human epidermal melanocytes (HEM cells (control were exposed to selected far infrared light (3400nm, 3600nm, 3800nm, 3900nm, 4100nm and 4300nm and visible and near infrared wavelengths (466nm, 585nm, 626nm, 810nm, 850nm and 950nm. The optical intensities of LEDs used for exposures were in the range of 15µW to 30µW. Cellular morphological changes of exposed and sham-exposed cells were evaluated using light microscopy. The cytotoxic effects of these low intensity light exposures on human cancer and normal cell lines were quantitatively determined by Lactate dehydrogenase (LDH cytotoxic activity and PrestoBlueTM cell viability assays. Findings reveal that far-infrared exposures were able to reduce cell viability of MCF7 cells as measured by increased LDH release activity and PrestoBlueTM assays. Further investigation of the effects of light irradiation on different types of cancer cells, study of possible signaling pathways affected by electromagnetic radiation (EMR and in vivo experimentation are required in order to draw a firm conclusion about the efficacy of low intensity light as an alternative non-invasive cancer treatment.

  10. The Cytotoxic Effects of Low Intensity Visible and Infrared Light on Human Breast Cancer (MCF7 cells

    Directory of Open Access Journals (Sweden)

    P Peidaee

    2013-03-01

    Full Text Available A concept of using low intensity light therapy (LILT as an alternative approach to cancer treatment is at early stages of development; while the therapeutic effects of LILT as a non-invasive treatment modality for localized joint and soft tissue wound healing are widely corroborated. The LEDs-based exposure system was designed and constructed to irradiate the selected cancer and normal cells and evaluate the biological effects induced by light exposures in visible and infrared light range. In this study, human breast cancer (MCF7 cells and human epidermal melanocytes (HEM cells (control were exposed to selected far infrared light (3400nm, 3600nm, 3800nm, 3900nm, 4100nm and 4300nm and visible and near infrared wavelengths (466nm, 585nm, 626nm, 810nm, 850nm and 950nm. The optical intensities of LEDs used for exposures were in the range of 15µW to 30µW. Cellular morphological changes of exposed and sham-exposed cells were evaluated using light microscopy. The cytotoxic effects of these low intensity light exposures on human cancer and normal cell lines were quantitatively determined by Lactate dehydrogenase (LDH cytotoxic activity and PrestoBlueTM cell viability assays. Findings reveal that far-infrared exposures were able to reduce cell viability of MCF7 cells as measured by increased LDH release activity and PrestoBlueTM assays. Further investigation of the effects of light irradiation on different types of cancer cells, study of possible signaling pathways affected by electromagnetic radiation (EMR and in vivo experimentation are required in order to draw a firm conclusion about the efficacy of low intensity light as an alternative non-invasive cancer treatment.

  11. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Martin Weiss

    Full Text Available One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP, is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS. In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH. Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  12. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Science.gov (United States)

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  13. Chemosensitizing effects of carbon-based nanomaterials in cancer cells: enhanced apoptosis and inhibition of proliferation as underlying mechanisms

    Science.gov (United States)

    Erdmann, Kati; Ringel, Jessica; Hampel, Silke; Rieger, Christiane; Huebner, Doreen; Wirth, Manfred P.; Fuessel, Susanne

    2014-10-01

    Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight (EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation, clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion, the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel

  14. Anti-Cancer Effect of Lambertianic Acid by Inhibiting the AR in LNCaP Cells

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    Myoung-Sun Lee

    2016-07-01

    Full Text Available Lambertianic acid (LA is known to have anti-allergic and antibacterial effects. However, the anticancer activities and mechanism of action of LA have not been investigated. Therefore, the anticancer effects and mechanism of LA are investigated in this study. LA decreased not only AR protein levels, but also cellular and secretory levels of PSA. Furthermore, LA inhibited nuclear translocation of the AR induced by mibolerone. LA suppressed cell proliferation by inducing G1 arrest, downregulating CDK4/6 and cyclin D1 and activating p53 and its downstream molecules, p21 and p27. LA induced apoptosis and the expression of related proteins, including cleaved caspase-9 and -3, c-PARP and BAX, and inhibited BCl-2. The role of AR in LA-induced apoptosis was assessed by using siRNA. Collectively, these findings suggest that LA exerts the anticancer effect by inhibiting AR and is a valuable therapeutic agent in prostate cancer treatment.

  15. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Reem T. Attia

    2016-06-01

    Full Text Available Background. Glufosfamide (GLU is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to the β-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects. The main objective of the current study is to assess the cytotoxic potential of GLU for the first time in prostate cancer (PC cells representing different stages of the tumor. Furthermore, this study examined the potential synergistic activity of GLU in combination with docetaxel (DOC. Methods. Two different cell lines were used, LNCaP and PC-3. Concentration-response curves were assessed. The tested groups per cell line were, control, GLU, DOC and combination. Treatment duration was 72 h. Cytotoxicity was assessed using sulforhodamine B (SRB assay and half maximal inhibitory concentration (IC50 was calculated. Synergy analyses were performed using Calcusyn®software. Subsequent mechanistic studies included β-glucosidase activity assay, glucose uptake and apoptosis studies, namely annexin V-FITC assay and the protein expression of mitochondrial pathway signals including Bcl-2, Bax, Caspase 9 and 3 were assessed. Data are presented as mean ± SD; comparisons were carried out using one way analysis of variance (ANOVA followed by Tukey-Kramer’s test for post hoc analysis. Results. GLU induced cytotoxicity in both cell lines in a concentration-dependent manner. The IC50 in PC-3 cells was significantly lower by 19% when compared to that of LNCaP cells. The IC50 of combining both drugs showed comparable effect to DOC in PC-3 but was tremendously lowered by 49% compared to the same group in LNCaP cell line. β-glucosidase activity was higher in LNCaP by about 67% compared to that determined in PC-3 cells while the glucose uptake in PC-3 cells was almost 2 folds that found in LNCaP cells. These results were directly correlated to the efficacy of GLU in each cell line. Treatment of PC cells with GLU as single

  16. Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship

    DEFF Research Database (Denmark)

    Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna

    2015-01-01

    -induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. CONCLUSION: As exercise training may have the potential to ameliorate...... and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship......., are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment...

  17. Dual effect of metformin on growth inhibition and oestradiol production in breast cancer cells.

    Science.gov (United States)

    Rice, S; Pellat, L; Ahmetaga, A; Bano, G; Mason, H D; Whitehead, S A

    2015-04-01

    Evidence has been accumulating for a role for metformin in reducing breast cancer risk in post-menopausal women. It inhibits growth of breast cancer cells via several mechanisms, primarily the AMPK/mTOR signalling pathway. Another possible protective mechanism may be the ability of metformin to inhibit aromatase activity. In the present study, we investigated the effects of metformin on the basal growth of MCF-7 cells, after oestradiol (E2) stimulation and after the inhibition of mTOR by rapamycin. Secondly, we investigated the effects of metformin on the activity of a number of steroidogenic enzymes and the mRNA expression of aromatase and steroid sulphatase (STS). High doses of metformin significantly inhibited both basal and oestrogen-stimulated cell division. Low-dose rapamycin (10-10 M) did not inhibit growth, but the addition of metformin induced a significant reduction in growth. High-dose rapamycin (10-8 M) inhibited growth, and this was further attenuated by the addition of metformin. Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17β-hydroxysteroid dehydrogenase/sulphatase to E2. This attenuation was via a downregulation in the expression of total aromatase mRNA and promoter II, whilst the expression of sulphatase was unaffected by metformin. In conclusion, plasma levels of metformin have a dual therapeutic action, first by directly inhibiting cell proliferation which can be augmented by rapamycin analogues, and secondly, by inhibiting aromatase activity and reducing the local conversion of androgens to E2.

  18. Apoptosis Effect of Girinimbine Isolated from Murraya koenigii on Lung Cancer Cells In Vitro

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    Syam Mohan

    2013-01-01

    Full Text Available Murraya koenigii Spreng has been traditionally claimed as a remedy for cancer. The current study investigated the anticancer effects of girinimbine, a carbazole alkaloid isolated from Murraya koenigii Spreng, on A549 lung cancer cells in relation to apoptotic mechanistic pathway. Girinimbine was isolated from Murraya koenigii Spreng. The antiproliferative activity was assayed using MTT and the apoptosis detection was done by annexin V and lysosomal stability assays. Multiparameter cytotoxicity assays were performed to investigate the change in mitochondrial membrane potential and cytochrome c translocation. ROS, caspase, and human apoptosis proteome profiler assays were done to investigate the apoptotic mechanism of cell death. The MTT assay revealed that the girinimbine induces cell death with an IC50 of 19.01 μM. A significant induction of early phase of apoptosis was shown by annexin V and lysosomal stability assays. After 24 h treatment with 19.01 μM of girinimbine, decrease in the nuclear area and increase in mitochondrial membrane potential and plasma membrane permeability were readily visible. Moreover the translocation of cytochrome c also was observed. Girinimbine mediates its antiproliferative and apoptotic effects through up- and downregulation of apoptotic and antiapoptotic proteins. There was a significant involvement of both intrinsic and extrinsic pathways. Moreover, the upregulation of p53 as well as the cell proliferation repressor proteins, p27 and p21, and the significant role of insulin/IGF-1 signaling were also identified. Moreover the caspases 3 and 8 were found to be significantly activated. Our results taken together indicated that girinimbine may be a potential agent for anticancer drug development.

  19. Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells.

    Science.gov (United States)

    Cai, Hao; Zhang, Yunhui; Han, Tianxiang Kevin; Everett, Ruth S; Thakker, Dhiren R

    2016-05-01

    The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation-selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation-selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3-BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT-20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.

  20. Killing effect of different doses of preoperative iodine 131 therapy on thyroid cancer cells and its effect on salivary gland function

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zheng; Tao Pu; Yi Luo; Xing-An Zhang; Zu-Mao Li

    2015-01-01

    Objective:To study the killing effect of different doses of preoperative iodine 131 therapy on thyroid cancer cells and its effect on salivary gland function.Methods:Patients diagnosed with thyroid cancer in our hospital from May 2013 to June 2014 were enrolled for study, given preoperative iodine 131 therapy and randomly divided into control group, low dose group, middle dose group and high dose group. Then cell apoptotic rate, cell cycle, cancer promoting gene and cancer suppressor gene expression in thyroid carcinoma tissue as well as salivary gland function were detected.Results: (1) cancer cell killing effect: compared with control group, cell apoptotic rates and number of cells in G0/G1 phase of low dose group, middle dose group and high dose group increased, number of cells in S and G2/M phase decreased, BRAF, Livin, MCM7 and CDK2 expression decreased, CCNG2 and PTEN expression increased; cell killing effect of middle dose group and high dose group were better than that of low dose group, and cell killing effect of middle dose group and high dose group had no differences; (2) salivary gland function: compared with control group, UI and SR in bilateral parotid and bilateral submandibular glands of low dose group, middle dose group and high dose group decreased; salivary gland damage effect of low dose group and middle dose group were weaker than that of high dose group, and salivary gland damage effect of low dose group and middle dose group had no differences.Conclusion:Middle dose of iodine 131 can take the killing effect on cancer cells and the protective effect on salivary glands into account; it’s an ideal dosage for preoperative iodine 131 internal radiation therapy of thyroid cancer patients.

  1. Effect of melamine on [Ca(2+)]i and viability in PC3 human prostate cancer cells.

    Science.gov (United States)

    Yu, Chia-Cheng; Chou, Chiang-Ting; Sun, Te-Kung; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Wang, Jue-Long; Tseng, Hui-Wen; Kuo, Chun-Chi; Chen, Fu-An; Kuo, Daih-Huang; Shieh, Pochuen; Jan, Chung-Ren

    2014-11-01

    Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca(2+)]i rises concentration-dependently. Melamine-evoked Ca(2+) entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin inhibited melamine-evoked [Ca(2+)]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca(2+)]i rise. Melamine at 500-800μM decreased cell viability, which was not reversed by pretreatment with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca(2+)]i rises by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum, and Ca(2+) entry via protein kinase C-regulated store-operated Ca(2+) entry. Melamine also caused Ca(2+)-independent cell death.

  2. Silencing overexpression of FXYD3 protein in breast cancer cells amplifies effects of doxorubicin and γ-radiation on Na(+)/K(+)-ATPase and cell survival.

    Science.gov (United States)

    Liu, Chia-Chi; Teh, Rachel; Mozar, Christine A; Baxter, Robert C; Rasmussen, Helge H

    2016-01-01

    FXYD3, also known as mammary tumor protein 8, is overexpressed in several common cancers, including in many breast cancers. We examined if such overexpression might protect Na(+)/K(+)-ATPase and cancer cells against the high levels of oxidative stress characteristic of many tumors and often induced by cancer treatments. We measured FXYD3 expression, Na(+)/K(+)-ATPase activity and glutathionylation of the β1 subunit of Na(+)/K(+)-ATPase, a reversible oxidative modification that inhibits the ATPase, in MCF-7 and MDA-MB-468 cells. Expression of FXYD3 was suppressed by transfection with FXYD3 siRNA. A colorimetric end-point assay was used to estimate cell viability. Apoptosis was estimated by caspase 3/7 (DEVDase) activation using a Caspase fluorogenic substrate kit. Expression of FXYD3 in MCF-7 breast cancer cells was ~eightfold and ~twofold higher than in non-cancer MCF-10A cells and MDA-MB-468 cancer cells, respectively. A ~50 % reduction in FXYD3 expression increased glutathionylation of the β1 Na(+)/K(+)-ATPase subunit and reduced Na(+)/K(+)-ATPase activity by ~50 %, consistent with the role of FXYD3 to facilitate reversal of glutathionylation of the β1 subunit of Na(+)/K(+)-ATPase and glutathionylation-induced inhibition of Na(+)/K(+)-ATPase. Treatment of MCF-7 and MDA-MB- 468 cells with doxorubicin or γ-radiation decreased cell viability and induced apoptosis. The treatments upregulated FXYD3 expression in MCF-7 but not in MDA-MB-468 cells and suppression of FXYD3 in MCF-7 but not in MDA-MB-468 cells amplified effects of treatments on Na(+)/K(+)-ATPase activity and treatment-induced cell death and apoptosis. Overexpression of FXYD3 may be a marker of resistance to cancer treatments and a potentially important therapeutic target.

  3. Pharmacological levels of Withaferin A (Withania somnifera trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Katarzyna Szarc vel Szic

    Full Text Available Withaferin A (WA isolated from Withania somnifera (Ashwagandha has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8, cell adhesion molecules (integrins, laminins, pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1. In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors

  4. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

    2015-06-16

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

  5. Inflammation and cancer stem cells.

    Science.gov (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.

  6. Cytotoxic effect of silver nanoparticles synthesized from Padina tetrastromatica on breast cancer cell line

    Science.gov (United States)

    Gnana Selvi, B. Clara; Madhavan, J.; Santhanam, Amutha

    2016-09-01

    In recent years researchers were attracted towards marine sources due to the presence of active components in it. Seaweeds were widely used in pharmaceutical research for their known biological activities. The biological synthesis method of silver nanoparticles (AgNPs) using Padina tetrastromatica seaweed extract and their cytotoxicity against breast cancer MCF-7 cells was reported in this study. The synthesized AgNPs using seaweed extract were subjected to x-ray diffraction, UV-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscope, energy dispersive x-ray, zeta potential to elucidate the structural, morphology, size as well as surface potential parameters. An absorption peak at 430 nm in UV-visible spectrum reveals the excitation and surface plasmon resonance of AgNPs. FE-SEM micrographs exhibits the biosynthesized AgNPs, which are pre-dominantly round shaped and the size ranges between 40-50 nm. The zeta potential value of -27.6 mV confirms the stable nature of biosynthesized silver nanoparticles. Furthermore, the biological synthesized Ag NPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and the inhibitory concentration (IC50) was found for AgNPs against MCF-7 at 24 h incubation. Biological method of synthesizing silver nanoparticles shows a environmental friendly property which helps in effective electrifying usage in many fields.

  7. Gemcitabine-loaded smart carbon nanotubes for effective targeting to cancer cells.

    Science.gov (United States)

    Singh, Ravendra; Mehra, Neelesh Kumar; Jain, Vikas; Jain, Narendra Kumar

    2013-07-01

    Carbon nanotubes (CNTs) are the three-dimensional sp(2) hybridized nano-containers that have attracted considerable interest in drug delivery by offering potential advantages such as biocompatibility, non-immunogenicity, high loading efficiency, intrinsic stability and low toxicities. The aim of the present investigation was to assess the potential of gemcitabine-loaded folic acid (FA) conjugated multi-walled CNTs (GEM/FA-NT) for targeting to breast cancer cells. Pristine MWCNTs was functionalized by FA followed by carboxylation, acylation and amidation and characterized by electron microscopy, FT-IR spectroscopy, X-ray diffraction, entrapment efficiency, cytotoxicity and in vivo studies. FDA-approved GEM was loaded to the purified (GEM-NT) and GEM/FA-NT, and % entrapment efficiency was found to be approximately 71.60 ± 0.25 and 79.60 ± 0.45, respectively. The developed formulation GEM/FA-NT was found to have significantly less hemolytic toxicity (8.23 ± 0.65) as compared to free GEM (17.34 ± 0.56). The in vitro release was found to be in sustained pattern at the lysosomal pH, which depicts more cytotoxic response on human breast cancer cell line (MCF-7). It may be interpreted that the GEM/FA-NT formulation is capable to carry drug and deliver it selectively at the tumor site while minimizing side effects and thus holds promise in chemotherapy.

  8. TJ-41 Induces Apoptosis and Potentiates the Apoptotic Effects of 5-FU in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Suresh Volate

    2009-01-01

    Full Text Available Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer cells lines. TJ-41 inhibited the proliferation of human breast cancer cell lines dose dependently. Flow cytometric analysis showed that this decrease in DNA synthesis is to be associated with induction of apoptosis. In both cell lines, apoptosis was abolished by caspase-9 inhibitor Z-LEHD-fmk but was weakly inhibited by caspase-8 inhibitor Z-IETD-fmk, indicating that caspase-9 activation was involved in TJ-41 induced apoptosis. Additionally, TJ-41 stimulated phosphorylation of c-Jun NH2-terminal kinase (JNK and pretreatment of breast cancer cells with JNK inhibitor SP600125 completely abolished TJ-41 induced apoptosis. Our data also demonstrate that combined treatment of TJ-41 and 5-FU significantly potentiates the apoptotic effects of 5-FU in both breast cancer cell lines. Taken together, these data suggest that TJ-41 might provide a novel chemotherapeutic treatment for breast cancer.

  9. Effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients’ prognosis

    Institute of Scientific and Technical Information of China (English)

    Xin-Cheng Shu; Ping Gao; Xin-Jua Zuo

    2016-01-01

    Objective:To study the effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients' prognosis.Methods:A total of78 cases of patients with colon cancer who received radical surgery of colon cancer assisted by postoperative chemotherapy in our hospital from May 2012 to December 2014 were selected for treatment and randomly divided into two groups, combined treatment group received chemotherapy combined with cascade primed immune cell therapy, simple chemotherapy group received FOLFOX chemotherapy, and then serum tumor marker contents and angiogenesis molecule contents as well as red blood cell immune function indicators in peripheral blood were detected.Results:Serum tumor markers CCSA-2, CCSA-3, CCSA-4, PTN, NGAL and sMICA as well as angiogenesis molecules VEGF, FGF10, sICAM-1, sVCAM-1, Musashi1 and Dkk1 contents of combined treatment group were lower than those of conventional chemotherapy group; the proportion of CR1, CR3, CD58 and CD59 as well as the rosette formation rates of red blood cell C3b receptor and immune complex in peripheral blood of combined treatment group were significantly higher than those of conventional chemotherapy group.Conclusions:Chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy helps to kill tumor cells and inhibit angiogenesis while enhance red blood cell immune function, and it can improve the prognosis of radical surgery of colon cancer.

  10. Effect of surgical wound fluids after intraoperative electron radiotherapy on the cancer stem cell phenotype in a panel of human breast cancer cell lines

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    Zaleska, Karolina; Suchorska, Wiktoria Maria; Przybyła, Anna; Murawa, Dawid

    2016-01-01

    The wound healing process after surgery alters the area surrounding the original tumor and around the scar, and the modified microenvironment is more favorable for tumor recurrence. Intraoperative radiotherapy (IORT) is one of the more novel strategies in breast cancer (BC) treatment. Irradiation during surgery has effects on the tumor microenvironment, abrogating the proliferative cascade induced by surgical wound healing. The aim of the present study was to determine the effect of surgical wound fluids from IOERT treatment (RT-WF) compared with wound fluids from conservative-breast surgery only (WF) on the cancer stem cell phenotype in a panel of BC cell lines. Post-operative wound fluids were derived from patients with BC who underwent a tumor resection (quadrantectomy) plus intraoperative electron radiotherapy using a single dose of ≤10 Gy on the tumor bed and surrounding tissues, or from those who underwent a tumor resection without IOERT. Cell lines were incubated with 10% wound fluids, and after 4 days, the cluster of differentiation (CD)44+/CD24−/low phenotype and aldehyde dehydrogenase 1 (ALDH1) activity were determined by flow cytometry. The two types of fluid each affected the CD44+/CD24−/low phenotype. The results varied markedly between each cell line, even for the same histological subtypes. RT-WF decreased the CD44+/CD24−/low populations in the basal-like BT-549 and MDA-MB-468 cell lines, whereas in the luminal type MCF7 cell line, the two fluids inhibited these populations. The HER-OE subtypes harbored a minimal CD44+/CD24−/low population, but the growth of SK-BR-3 was stimulated by the two post-operative fluids. WF exhibited a stronger effect on ALDH1 activity compared with RT-WF. The stimulatory effect was dependent on the histological subtype of the cell line and the strongest dependence was observed in luminal subtypes characterized by low dehydrogenase activity in the control group. The present results enable a better understanding of

  11. Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells.

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    Shin, Ji-Ae; Shim, Jung-Hyun; Choi, Eun-Sun; Leem, Dae-Ho; Kwon, Ki Han; Lee, Syng-Ook; Safe, Stephen; Cho, Nam-Pyo; Cho, Sung-Dae

    2011-09-01

    Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC6H5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway.

  12. Immunology in the clinic review series; focus on cancer: double trouble for tumours: bi-functional and redirected T cells as effective cancer immunotherapies.

    Science.gov (United States)

    Marr, L A; Gilham, D E; Campbell, J D M; Fraser, A R

    2012-02-01

    Cancer is one of the most important pathological conditions facing mankind in the 21st century, and is likely to become the most important cause of death as improvements continue in health, diet and life expectancy. The immune response is responsible for controlling nascent cancer through immunosurveillance. If tumours escape this control, they can develop into clinical cancer. Although surgery and chemo- or radiotherapy have improved survival rates significantly, there is a drive to reharness immune responses to treat disease. As T cells are one of the key immune cells in controlling cancer, research is under way to enhance their function and improve tumour targeting. This can be achieved by transduction with tumour-specific T cell receptor (TCR) or chimaeric antigen receptors (CAR) to generate redirected T cells. Virus-specific cells can also be transduced with TCR or CAR to create bi-functional T cells with specificity for both virus and tumour. In this review we outline the development and optimization of redirected and bi-functional T cells, and outline the results from current clinical trials using these cells. From this we discuss the challenges involved in generating effective anti-tumour responses while avoiding concomitant damage to normal tissues and organs.

  13. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice

    Science.gov (United States)

    Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

    2017-01-01

    Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer. PMID:28252027

  14. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells.

    Science.gov (United States)

    Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  15. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

    Directory of Open Access Journals (Sweden)

    Vladimir Tolstikov

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  16. Anti-proliferation effects of benzimidazole derivatives on HCT-116 colon cancer and MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Al-Douh, Mohammed Hadi; Sahib, Hayder B; Osman, Hasnah; Abd Hamid, Shafida; Salhimi, Salizawati M

    2012-01-01

    Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an IC50 value of 16.2 ± 3.85 μg/mL and benzimidazole 1 a value of 28.5 ± 2.91 μg/mL, while that for benzimidazole 4 was 24.08 ± 0.31 μg/mL. In the MCF-7 cell line, benzimidazole 4 had an IC50 value of 8.86 ± 1.10 μg/mL, benzimidazole 2 a value of 30.29 ± 6.39 μg/mL, and benzimidazole 1 a value of 31.2 ± 4.49 μg/mL. Benzimidazole 3 exerted no cytotoxicity in either of the cell lines, with IC50 values >50 μg/mL. The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers.

  17. Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK.

    Science.gov (United States)

    Zhang, Bei; Wang, Xueya; Cai, Fengfeng; Chen, Weijie; Loesch, Uli; Bitzer, Johannes; Zhong, Xiao Yan

    2012-12-01

    This study investigated the anticancer effect and mechanism of salinomycin, a selective inhibitor of cancer stem cell, on human ovarian cancer cell line OV2008 in vitro and in vivo. The growth inhibitory effect of salinomycin on ovarian cancer cell line OV2008 was determined by measuring cell viability using the resazurin reduction assay. Apoptotic nuclear morphology was visualized by 4,6-diamino-2-phenylindole staining technique. The percentages of apoptotic cells and cell cycle parameters were detected by flow cytometry. The activity of p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Bio-Plex phosphoprotein assay. In vivo activity of salinomycin was assayed through tumor growth. Salinomycin caused concentration- (0.01-200 μM) and time-dependent (24-72 h) growth inhibitory effects in OV2008. Cell nuclear morphology observations showed that salinomycin-treated OV2008 cells displayed typical apoptotic characteristics. Salinomycin significantly increased the percentages of apoptotic cells in OV2008, showing a concentration- and time-dependent manner. There was no cell cycle arrest in the G1/G0, S, and G2/M phases between salinomycin-treated cells and control cells. Salinomycin also enhanced the phosphorylation of p38 MAPK. Moreover, salinomycin significantly inhibited the growth of the ovarian xenograft tumors. Salinomycin exhibited significant growth inhibition and induction of apoptosis in the human ovarian cancer cell line OV2008. The data suggested that salinomycin-induced apoptosis in OV2008 might be associated with activating p38 MAPK and merits further investigations.

  18. Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ming-Quan Song; Jin-Shui Zhu; Jin-Lian Chen; Long Wang; Wei Da; Li Zhu; Wei-Ping Zhang

    2007-01-01

    AIM:To investigate the synergistic effect of oxymatrine (OM) and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cell lines SGC-7901,MKN-45,MKN-74.METHODS:Human gastric cancer lines SGC-7901,MKN-45,MKN-74 were treated with OM in the absence and presence of NM-3. The inhibitory rates were detected by MTT assay. Synergistic effect of OM and NM-3 on the growth of survivin,bcl-2,bax and p53 in SGC-7901 cells were examined by semiquantitative RT-PCR and Western blotting,and their growth inhibitory effects were also observed on SGC-7901 tumor xenograft in nude mice.RESULTS:OM combined with NM-3 exhibited a synergistic inhibitory effect on the growth of SGC-7901,MKN-45 and MKN-74 cells in a time-dependent manner. Twenty-four hours after treatment with OM,NM-3 alone and their combination,mRNA expression of survivin and bcl-2 in SGC-7901 cells decreased,p53 mRNA expression increased. OM (4 g/L) combined with NM-3 significantly increased the expression of p53 mRNA and decreased the expression of survivin and bcl-2 compared with either agent alone (193% ± 34% vs 129% ± 12%; 44% ± 18% vs 92% ± 18%; 36 ± 17% vs 93% ± 23%, P<0.05). Western blotting showed that the synergistic effect of OM and NM-3 on protein translation of survivin, bcl-2 and p53 was in accordance with their mRNAs. Furthermore, OM/NM-3 combination obviously exhibited antitumor growth effect in xenografted human gastric cancer cells SGC-7901 compared with either agent alone.CONCLUSION:OM combined with NM-3 has synergistic inhibitory effects on human gastric cancer cells in vitroand can suppress the growth of xenografted human gastric cancer cells SGC-7901 in vivo.

  19. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  20. Effect of D-allose on prostate cancer cell lines: phospholipid profiling by nanoflow liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Jeong, Rae Ung; Lim, Sangsoo; Kim, Myoung Ok; Moon, Myeong Hee

    2011-08-01

    D-Allose, a rare, naturally occurring monosaccharide, is known to exert anti-proliferative effects on cancer cells. The effects of D-allose on the cellular membranes of hormone-refractory prostate cancer cell line (DU145), hormone-sensitive prostate cancer cell line (LNCaP), and normal prostate epithelial cells (PrEC) were studied at the molecular level by phospholipid (PL) profiling using a shotgun lipidomic method. The molecular structures of 85 PL species including 23 phosphatidylcholines, 12 phosphatidylethanolamines (PEs), 11 phosphatidylserines (PSs), 16 phosphatidylinositols, 9 phosphatidic acids (PAs), and 14 phosphatidylglycerols (PGs) were identified by data-dependent collision-induced dissociation of nanoflow liquid chromatography-tandem mass spectrometry, and the PL amounts were quantified. The addition of D-allose to prostate cancer cell lines during their growth phases had negligible or decreased effects on the relative regulation of PL species, but several new PS molecules (two for DU145 and three for LNCaP) emerged. In contrast, experiments on the PrEC cell line revealed that some high abundant species (14:0/14:0-PE, 16:2/16:0-PG, and 20:6/18:1-PA) showed significant increases in concentration. These findings support a mechanism for the anti-proliferative effect of D-allose on prostate cancer cell lines that involves the induction of programmed cell death since PS molecules are known to induce apoptosis. Principal component analysis was carried out to examine differences in PL distributions among the three cell lines promoted by D-allose.