Suppression of anti-microtubule agent-induced apoptosis by nitric oxide: possible mechanism of a new drug resistance

Japanese Journal of Cancer Research : Gann
T OguraH Esumi

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-1beta 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.

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Citations

Aug 24, 2005·Nitric Oxide : Biology and Chemistry·Gabriela Di VenosaAlcira Batlle
Nov 28, 2002·International Journal of Cancer. Journal International Du Cancer·Yoshiyuki IshiiHiroyasu Esumi
May 17, 2000·Journal of Hematotherapy & Stem Cell Research·T KajiumeN Kataoka

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis