Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Hu, Lixia; Du, Yingying; Zhang, Ying; Pan, Yueyin

doi:10.7314/apjcp.2012.13.11.5903

Cited by 18 publications

(12 citation statements)

References 45 publications

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“…Therefore, the difference between aspirin and diclofenac against the fibroblast cell growth may be related to the concentration of the drug that deposited in fibroblast cells. The results of NSAIDs on the mammary cell growth do not agree the previous reports that showed aspirin induced breast cancer apoptosis in presence of over-expression of Bcl-2 gene (Choi et al, 2013; Hu et al, 2012). Therefore, NSAIDs inhibit the growth of breast cell cancer in specific experimental models, otherwise, their cytotoxic effect is missed.…”

Section: Discussioncontrasting

confidence: 95%

Antiproliferative effects of aspirin and diclofenac against the growth of cancer and fibroblast cells: In vitro comparative study

Al-Nimer

Hameed

Mahmood

2015

Saudi Pharmaceutical Journal

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Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the growth of several cancer cell lines. The aim of this study is to compare the cytotoxic effect of aspirin with diclofenac on the growth of HeLa cell, mammary cell carcinoma, rhabdomyosarcoma and fibroblast cell lines in the culture media. The cells are cultured in RPMI-1640 culture media supplemented with 5% fetal calf serum and antibiotics. Aspirin (5 mg/well) and diclofenac (0.625 mg/well) significantly inhibit the growth of HeLa, rhabdomyosarcoma and fibroblast cells. The cytotoxic effect of aspirin against rhabdomyosarcoma is significantly (p < 0.001) higher than that of diclofenac with a potency approximated 2.6. It concludes that aspirin and diclofenac inhibit the growth of fibroblast and cancer cell by inhibiting the up-regulation of cyclooxygenases enzymes in cancer cells. Aspirin is more effective than diclofenac against the growth of rhabdomyosarcoma cell line.

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Section: Discussioncontrasting

confidence: 95%

Antiproliferative effects of aspirin and diclofenac against the growth of cancer and fibroblast cells: In vitro comparative study

Al-Nimer

Hameed

Mahmood

2015

Saudi Pharmaceutical Journal

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“…There is increasing interest in cancer prevention and in the drugs that, used in low doses, either alone or in combination, which have different modes of action and low toxicity, act as chemopreventive agents (47). Therefore, the present study investigated other molecules, which are used for the treatment of well-known pathological diseases and have effects on cancer cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Shen

Yuan²,

et al. 2012

Molecular Medicine Reports

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Abstract. Breast carcinoma is the leading cause of cancer-associated mortality in female individuals worldwide. Previous studies have investigated the pro-apoptotic and antimetastatic effects of statins, and have demonstrated that simvastatin exhibits antitumor activity and potent chemopreventive effects. However, the mechanism underlying the effects of simvastatin in breast cancer remains to be elucidated. The present study demonstrated that simvastatin inhibited the proliferation of MDA-MB-231 human breast cancer cells in a dose-dependent manner, decreased the protein expression of B cell lymphoma 2 (Bcl-2) and increased the protein expression of Bcl-2-associated X protein in timeand dose-dependent manners. In addition, simvastatin arrested cells in the G 0 /G 1 phase of the cell cycle, downregulated the protein expression levels of cyclin D1 and cyclin-dependent kinase (CDK)2, mediated the mitochondria-dependent caspase cascade by increasing the protein expression levels of caspase-3, -8 and -9, and downregulated the protein expression of X-linked inhibitor of apoptosis, which induced cell apoptosis. In addition, simvastatin decreased the protein expression of matrix metalloproteinase (MMP)-2 and suppressed the activation of nuclear factor (NF)-κB in the MDA-MB-231 cells. Taken together, these results demonstrated that the antitumor effect of simvastatin in the human MDA-MB-231 breast cancer cell line was via the inhibition of cell proliferation, affecting the cell cycle, downregulating the expression levels of cyclin D1 and CDKs, inducing apoptosis and decreasing the expression of MMP-2, possibly by inhibiting the activation of NF-κB. Statin treatment may provide a novel therapeutic approach for the treatment of breast cancer.

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“…Therapeutic strategies using a combination of drugs in order to enhance the efficacy of cancer treatment have recently garnered attention. The drugs may act together synergistically to inhibit tumor progression through the regulation of various signaling pathways, or reverse the cancer-specific upregulated cell proliferation or evasion of apoptosis (23). The present study chose to evaluate combinations of statin drugs, based upon previously reported cytotoxic experience in breast cancer cell lines (24,25).…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of combined treatment with simvastatin and exemestane on MCF-7 human breast cancer cells

Shen

Zhang

et al. 2012

Molecular Medicine Reports

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Breast cancer is associated with high levels of incidence, morbidity and mortality; therefore, the identification of effective chemopreventive strategies is crucial. It is important for clinicians to be able to identify the populations at risk who would benefit from chemoprevention, and the interventions that are effective and safe. The aim of the present study was to investigate the combined effects of simvastatin and exemestane on MCF-7 human breast cancer cells. The anti-proliferative effects of simvastatin and exemestane, alone and in combination, on the growth of MCF-7 human breast cancer cells were assessed by MTT assay. The synergism between the two drugs was determined in vitro using the combination index (CI) analysis. Cell cycle distribution and apoptosis were analyzed by flow cytometry, and alterations to the signaling pathway in MCF-7 cells were examined by immunoblotting following treatment with various regimens. The results of the MTT assay indicated that the combined treatment of simvastatin and exemestane significantly decreased the viability of MCF-7 estrogen receptor-positive (ER+) human breast cancer cells, as compared with those that were treated with the individual drugs (CI<1). In addition, coadministration of exemestane and simvastatin was shown to result in marked inhibition of tumor cell proliferation, significant cell cycle arrest at G0/G1 phase and induction of apoptosis, as compared with that of the control and individual drug-treated cells. Furthermore, the results of the present study indicated that these synergistic effects may be associated with the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein apoptotic pathway and the mitogen-activated protein kinase/mammalian target of rapamycin/p70S6 kinase growth pathway. The combination of exemestane and simvastatin generated synergistic effects on MCF-7 ER+ breast cancer cells, indicating that the combination of these drugs may be a potential therapeutic strategy for the treatment of hormone-dependent breast cancer. The combination of the two inhibitors markedly increased the efficacy, as compared with the single-agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer. The results of the present study suggested that this combination of drugs has therapeutic potential, and requires further mechanistic and biomarker investigations in clinical trials.

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Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Cited by 18 publications

References 45 publications

Antiproliferative effects of aspirin and diclofenac against the growth of cancer and fibroblast cells: In vitro comparative study

Antiproliferative effects of aspirin and diclofenac against the growth of cancer and fibroblast cells: In vitro comparative study

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Synergistic effects of combined treatment with simvastatin and exemestane on MCF-7 human breast cancer cells

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