Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells
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| collectionurl | https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection407072 |
| date | 2015-03-08 12:13:45 |
| format | Restricted Document |
| id | 11405 |
| institution | UniSZA |
| internalnotes | Aranovich A, Liu Q, Collins T, et al (2012). Differences in the mechanisms of proapoptotic BH3 proteins binding to Bcl-XL and Bcl-2 quantified in live MCF-7 cells. Molecular Cell, 45, 754-63. Bateman NW., Sun M, Hood BL, et al (2010). Defining central themes in breast cancer biology by differential proteomics: conserved regulation of cell spreading and focal adhesion kinase. J Proteome Res, 9, 5311-24. Boffa DJ, LuanF, Thomas D, et al (2004). Rapamycin inhibits the growth and metastatic progression of non-small cell lung cancer. Clin Cancer Res, 10, 293-300. Gelmann EP, Thompson EW, Sommers CL (1992). Invasive and metastatic properties of MCF-7 cells and rasH-transfected MCF-7 cell lines. Int J Cancer, 50, 665-9. Geoerger B, Kerr K, Tang CB, et al (2001). Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res, 61, 1527-32. Gibbons JJ, Abraham RT, Yu K (2009). Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol, 3, 3-17. Grünwald V, DeGraffenried L, Russel D, et al (2002). Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells. Cancer Res, 62, 6141-5. Guba M, von Breitenbuch P, Steinbauer M, et al (2002). Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nature Med, 8, 128-35. Hamelers IH, Van Schaik R, Sussenbach JS, Steenbergh PH (2003). 17β-Estradiol responsiveness of MCF-7 laboratory strains is dependent on an autocrine signal activating the IGF type I receptor. Cancer Cell Int, 3, 10. Hashemolhosseini S, Nagamine Y, Morley SJ, et al (1998). Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem, 273, 14424-9. Hidalgo M, Rowinsky EK (2000). The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene, 19, 6680-6. Hosoi H, Dilling MB, Shikata T, et al (1999). Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Cancer Res, 59, 886-94. Huang S, Liu LN, Hosoi H, et al (2001). p53/p21CIP1 cooperate in enforcing rapamycin-induced G1 arrest and determine the cellular response to rapamycin. Cancer Res, 61, 3373-81. Idris FM, Mansor WNAW, Irfan M, Jalal A, Jaafar H (2014). Rapamycin and PF4 induce apoptosis by upregulating Bax and down-regulating survivin in MNU-induced breast cancer. Asian Pac J Cancer Prev, 15, 3939-44. Kawamata S, Sakaida H, Hori T, et al (1998). The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines. Blood, 91, 561-9. Khemapech N, Pitchaiprasert S, Triratanachat S (2012). Prevalence and clinical significance of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) in clear cell carcinoma of the ovary. Asian Pac J Cancer Prev, 13, 6357-62. Lai D, Ho KC, Hao Y, Yang X (2011). Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res, 71, 2728-38. Law BK (2005). Rapamycin: an anti-cancer immunosuppressant? Crit Rev Oncol Hematol, 56, 47-60. Mahalati K, Kahan BD (2001). Clinical pharmacokinetics of sirolimus. Clin Pharmacokinetics, 40, 573-85. Noh WC, Mondesire WH, Peng J, et al (2004). Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res, 10, 1013-23. Rathmell WK, Wright TM, Rini BI (2005). Molecularly targeted therapy in renal cell carcinoma. Expert Rev Anticancer Ther, 5, 1031-40. Rizzieri DA, Feldman, E., DiPersio, J. F, et al (2008). A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res, 14, 2756-62. Sykes SM, Lane SW, Bullinger L, et al (2011). AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell, 146, 697-708. Soule H, Vazquez J, Long A, Albert S, Brennan M (1973). A human cell line from a pleural effusion derived from a breast carcinoma. J National Cancer Inst, 51, 1409-16. Thimmaiah KN, Easton JB, Houghton PJ (2010). Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling. Cancer Res, 70, 2000-9. Wang Y, Wang X, Zhao H, Liang B, Du Q (2012). Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer cells through NF-kappaB activation and Bcl-2 overexpression. J Chemotherapy, 24, 348-57. Wiedmann MW, Caca K (2005). Molecularly targeted therapy for gastrointestinal cancer. Current Cancer Drug Targets, 5, 171-93. Yaacob NS, Nasir R, Norazmi MN (2013). Influence of 17β-estradiol on 15-deoxy-Δ12, 14 prostaglandin J2-induced apoptosis in MCF-7 and MDA-MD-231 cells. Asian Pac J Cancer Prev, 14, 6761-7. Yu K, Toral-Barza L, Discafani C, et al (2001). mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocrine-Related Cancer, 8, 249-58. |
| originalfilename | 5638-01-FH02-FPSK-15-02626.jpg |
| person | UniSZA Unisza unisza |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=11405 |
| spelling | 11405 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=11405 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection407072 Restricted Document Article Journal UniSZA Unisza unisza image/jpeg inches 96 96 1417 63 63 749 2015-03-08 12:13:45 1417x749 5638-01-FH02-FPSK-15-02626.jpg UniSZA Private Access Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells Asian Pacific Journal of Cancer Prevention Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. MCF-7 cells were plated at a density of 15105 cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at 37oC, 5% CO2 and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The IC50 value of rapamycin on the MCF-7 cells was determined as 0.4μg/ml (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent. 15 24 10659-10663 Aranovich A, Liu Q, Collins T, et al (2012). Differences in the mechanisms of proapoptotic BH3 proteins binding to Bcl-XL and Bcl-2 quantified in live MCF-7 cells. Molecular Cell, 45, 754-63. Bateman NW., Sun M, Hood BL, et al (2010). Defining central themes in breast cancer biology by differential proteomics: conserved regulation of cell spreading and focal adhesion kinase. J Proteome Res, 9, 5311-24. Boffa DJ, LuanF, Thomas D, et al (2004). Rapamycin inhibits the growth and metastatic progression of non-small cell lung cancer. Clin Cancer Res, 10, 293-300. Gelmann EP, Thompson EW, Sommers CL (1992). Invasive and metastatic properties of MCF-7 cells and rasH-transfected MCF-7 cell lines. Int J Cancer, 50, 665-9. Geoerger B, Kerr K, Tang CB, et al (2001). Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res, 61, 1527-32. Gibbons JJ, Abraham RT, Yu K (2009). Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol, 3, 3-17. Grünwald V, DeGraffenried L, Russel D, et al (2002). Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells. Cancer Res, 62, 6141-5. Guba M, von Breitenbuch P, Steinbauer M, et al (2002). Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nature Med, 8, 128-35. Hamelers IH, Van Schaik R, Sussenbach JS, Steenbergh PH (2003). 17β-Estradiol responsiveness of MCF-7 laboratory strains is dependent on an autocrine signal activating the IGF type I receptor. Cancer Cell Int, 3, 10. Hashemolhosseini S, Nagamine Y, Morley SJ, et al (1998). Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem, 273, 14424-9. Hidalgo M, Rowinsky EK (2000). The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene, 19, 6680-6. Hosoi H, Dilling MB, Shikata T, et al (1999). Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Cancer Res, 59, 886-94. Huang S, Liu LN, Hosoi H, et al (2001). p53/p21CIP1 cooperate in enforcing rapamycin-induced G1 arrest and determine the cellular response to rapamycin. Cancer Res, 61, 3373-81. Idris FM, Mansor WNAW, Irfan M, Jalal A, Jaafar H (2014). Rapamycin and PF4 induce apoptosis by upregulating Bax and down-regulating survivin in MNU-induced breast cancer. Asian Pac J Cancer Prev, 15, 3939-44. Kawamata S, Sakaida H, Hori T, et al (1998). The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines. Blood, 91, 561-9. Khemapech N, Pitchaiprasert S, Triratanachat S (2012). Prevalence and clinical significance of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) in clear cell carcinoma of the ovary. Asian Pac J Cancer Prev, 13, 6357-62. Lai D, Ho KC, Hao Y, Yang X (2011). Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res, 71, 2728-38. Law BK (2005). Rapamycin: an anti-cancer immunosuppressant? Crit Rev Oncol Hematol, 56, 47-60. Mahalati K, Kahan BD (2001). Clinical pharmacokinetics of sirolimus. Clin Pharmacokinetics, 40, 573-85. Noh WC, Mondesire WH, Peng J, et al (2004). Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res, 10, 1013-23. Rathmell WK, Wright TM, Rini BI (2005). Molecularly targeted therapy in renal cell carcinoma. Expert Rev Anticancer Ther, 5, 1031-40. Rizzieri DA, Feldman, E., DiPersio, J. F, et al (2008). A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res, 14, 2756-62. Sykes SM, Lane SW, Bullinger L, et al (2011). AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell, 146, 697-708. Soule H, Vazquez J, Long A, Albert S, Brennan M (1973). A human cell line from a pleural effusion derived from a breast carcinoma. J National Cancer Inst, 51, 1409-16. Thimmaiah KN, Easton JB, Houghton PJ (2010). Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling. Cancer Res, 70, 2000-9. Wang Y, Wang X, Zhao H, Liang B, Du Q (2012). Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer cells through NF-kappaB activation and Bcl-2 overexpression. J Chemotherapy, 24, 348-57. Wiedmann MW, Caca K (2005). Molecularly targeted therapy for gastrointestinal cancer. Current Cancer Drug Targets, 5, 171-93. Yaacob NS, Nasir R, Norazmi MN (2013). Influence of 17β-estradiol on 15-deoxy-Δ12, 14 prostaglandin J2-induced apoptosis in MCF-7 and MDA-MD-231 cells. Asian Pac J Cancer Prev, 14, 6761-7. Yu K, Toral-Barza L, Discafani C, et al (2001). mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocrine-Related Cancer, 8, 249-58. |
| spellingShingle | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| summary | Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. MCF-7 cells were plated at a density of 15105 cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at 37oC, 5% CO2 and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The IC50 value of rapamycin on the MCF-7 cells was determined as 0.4μg/ml (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent. |
| title | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| title_full | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| title_fullStr | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| title_full_unstemmed | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| title_short | Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells |
| title_sort | effects of rapamycin on cell apoptosis in mcf-7 human breast cancer cells |