Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining.In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10？μM. Increasing concentration up to 30？μM increased the number of cell death. Whilst genistein alone at low concentration (≤10？μM) induced cell proliferation, addition of genistein (20？μM) 16？h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50？μM) induced necrotic cells.Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method could potentially be developed as an alternative strategy for treatment of p53 defective cancer cells.Most of chemotherapeutic drugs such as etoposide, cisplastin, doxorubicin and camptotechin induce DNA damage on cancer cells. These DNA (deoxy nucleid acid) damaging agents arrest or delay cell cycle progression, allowing time for DNA repair. This mechanism of repair functions to ensure that division only occur on cells carrying complete DNA, not mutated or damage. If the damage is beyond repair, the cells may permanently enter cellular senescence or undergo apoptosis [1,2]. The mechanism of cell cycle arrest is mediated by ATM (ataxia telangiectasia-mutated protein kinase) or ATR (ATM and Rad3-related protein kinase) through the activation of Ser/Thr kinases checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2). The activation of Chk1 and Chk2 in turn modulates phosphorylation events such as phosphorylation of cdc25 pho