The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21(WAF-1)) and anti-apoptotic protein (bcl-2) in breast cancer cells.
Cyclophosphamide (CYC), epirubicin (EPI) and 5-fluorouracil (5FU) are commonly used cytotoxic drugs for the treatment of breast cancer. The efficacy of these drugs in the induction of caspases (CPP-32), pro-apoptotic (p21(WAF-1)) and anti-apoptotic (bcl-2) proteins is tested in vitro on breast cancer cells lines MDA-MB-231 and MCF-7. The cell proliferation rate and the levels of CPP-32, p21(WAF-1) and bcl-2 are measured at 3, 6, 12 and 24 h. For MDA-MB-231 all three drugs caused significant inhibition in cell growth. CYC produces significant induction of CPP-32 at 3-6 h for MCF-7 only. For MDA-MB-231 and MCF-7, respectively, EPI induces CPP-32 at significant levels at 12-24 h and 6-12 h while 5FU creates induction for MDA-MB-231 at 3 h and for MCF-7 at 3-12 h. The levels of expression of p21(WAF-1) and bcl-2 for all test groups were significantly different from their respective control groups. In the case of MDA-MB-231, regression analysis reveals that changes in CPP-32 levels and p21(WAF-1) levels have a significant positive relationship. In all likelihood, other mechanisms of cell death are implicated in the antitumor effect of these drugs, beyond the activation of CPP-32 and p21(WAF-1) as described in this paper.
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis* / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis* / Q000096:biosynthesis; D003520:Cyclophosphamide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000032:analysis*; D004792:Enzyme Precursors / Q000032:analysis* / Q000096:biosynthesis; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D015251:Epirubicin; D003520:Cyclophosphamide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005472:Fluorouracil