The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21WAF-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.