Antioxidants enhance the susceptibility of colon carcinoma cells to 5-fluorouracil by augmenting the induction of the bax protein

5 Fluorouracil (5 FU), the most effective systemic chemotherapeutic agent i n the management of advanced colorectal carcinoma acts by inducing apoptosi s. Response rates, approximately 20% is improved by folinic acid. This stud y investigates similar modulation of 5 FU-induced apoptosis by oxidant quen ching. A five-fold reduction of intracellular oxidant levels by antioxidant s N-acetylcysteine and vitamin E did not induce apoptosis, it however augme nted pro-apoptotic bar protein expression, and apoptotic response to a non- toxic dose of 5 EU in the colorectal cancer cell lines cole 201 and cole 20 5. This suggests that reduction of intracellular levels of reactive oxygen species enhance susceptibility to 5 FU (apoptotic stimuli) by augmentation of bar expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.