ORIGINAL ARTICLE Apoptosis-Inducing Effect of Chemotherapeutic Agents Is

Abstract: Cancer chemotherapeutic strategies should be devised to provide higher tumor response and lower toxicity for combination chemotherapy. Genistein has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. The antitumor effects of genistein could be in part due to inac-tivation of NF-B activity. In contrast, chemotherapeutic agents in-advertently induce NF-B activity, which may lead to chemoresis-tance. In this study, we investigated whether the inactivation of NF-B by genistein would enhance the efficacy of chemotherapeutic agents. BxPC-3 pancreatic cancer cells were pretreated with 30 µmol/L genistein for 24 hours and then exposed to lower concentra-tions of chemotherapeutic agents for an additional 24 hours. Cell growth inhibition assay, apoptosis assay, and NF-B EMSA were performed. The combination of 30 µmol/L genistein with 1 nmol/L docetaxel or 100 nmol/L cisplatin elicited significantly greater inhi-bition of cell growth compared with either agent alone. The combi-nation treatment induced more apoptosis in BxPC-3 cells compared with single agents. Moreover, the NF-B activity was significantly increased within 2 hours of docetaxel or cisplatin treatment, and the NF-B–inducing activity of these agents was completely abrogated in cells pretreated with genistein. These results clearly suggest that genistein pretreatment, which inactivates NF-B activity, together with other cellular effects of genistein, may contribute to increased cell growth inhibition and apoptosis inducing effects of nontoxic doses of docetaxel and cisplatin, which could be a novel strategy for the treatment of pancreatic cancer