Suppression of Anti‐microtubule Agent‐induced Apoptosis by Nitric Oxide: Possible Mechanism of a New Drug Resistance

Abstract
The propensity of a cell to undergo apoptosis has been proposed to be a determinant of sensitivity to anti‐microtubule agents. The anti‐microtubule agents vincristine and paclitaxel induce key features of apoptosis, such as intranucleosomal DNA fragmentation and changes in nuclear morphology in the human neuroblastoma cell line, NB‐39‐nu. Nitric oxide (NO) generated from NO‐releasing drugs prevented anti‐microtubule agent‐induced apoptosis in this cell line. The mechanism of suppression of apoptosis by NO appears to be via the inhibition of an interleukin‐1β converting enzyme‐like protease cascade. This finding reveals a new biological function of NO, as well as a new molecular insight into resistance to chemotherapy with anti‐microtubule agents.