Suppression of anti-microtubule agent-induced apoptosis by nitric oxide: possible mechanism of a new drug resistance.
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.
Ogura
T
T
Investigative Treatment Division, National Cancer Center Research Institute East, Kashiwa, Chiba.
DeGeorge
G
G
Tatemichi
M
M
Esumi
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D014750:Vincristine; D026423:S-Nitroso-N-Acetylpenicillamine; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D010396:Penicillamine; D017239:Paclitaxel