Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture.
A hormone- and growth factor-stimulated NADH oxidase of the mammalian plasma membrane, constitutively activated in transformed cells, was inhibited preferentially in HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells, all of human origin, by the naturally occurring quinone analog capsaicin (8-methyl-N-vanillyl-6-noneamide), compared with plasma membranes from human mammary epithelial, rat liver, normal rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. With cells in culture, capsaicin preferentially inhibited growth of HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells but was largely without effect on the mammary epithelial cells, rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. Inhibited cells became smaller and cell death was accompanied by a condensed and fragmented appearance of the nuclear DNA, as revealed by fluorescence microscopy with 4',6-diamidino-2-phenylindole, suggestive of apoptosis. The findings correlate capsaicin inhibition of cell surface NADH oxidase activity and inhibition of growth that correlate with capsaicin-induced apoptosis.
Morré
D J
DJ
Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907.
Chueh
P J
PJ
Morré
D M
DM
D000230:Adenocarcinoma; D000818:Animals; D001943:Breast Neoplasms; D002211:Capsaicin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008099:Liver / Q000201:enzymology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010051:Ovarian Neoplasms; D051381:Rats; D014407:Tumor Cells, Cultured
D009097:Multienzyme Complexes; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D002211:Capsaicin