GENISTEIN POTENTIATES THE APOPTOTIC EFFECT OF 5-FLUOROURACYL IN COLON CANCER CELL LINES

Abstract

Transformation of normal cells, tumor progression and advanced metastasis involve a complex series of events such as genetic alterations, aberrant progression through cell cycle, induction of angiogenesis, inhibition of apoptosis and modification of cell adhesion. One of the most effective anticancer agents used to treat colon cancer is 5-Fluorouracyl (5-FU), but the resistance developed is an obstacle against the success of chemotherapy. Therefore, an emerging interest appeared in finding natural substances, such as genistein, for chemotherapeutic application in cancer. The purpose of this study was to determine whether different doses of genistein might increase the effects of 5-FU treatment on apoptosis in colon cancer cells and modulate the molecules involved. Real-time cell analysis (RTCA) by xCELLigence System was used to continuously monitor the compound-mediated cytotoxity effects in LoVo colon cancer cells. Flow cytometry assays were performed to evaluate cell cycle phases, apoptotic events and levels of nuclear antigen expression. In order to evaluate gene expression levels, isolated RNAs were reversed-transcribed, cDNAs amplified and assayed in Real Time PCR. Data obtained showed additional effects of GST to 5-FU treatments on the increase of apoptosis, and suggested alternative approaches to obtain a stronger anti-tumor response, when use lower concentrations of anti-cancer drugs.