Inhibition of apoptosis as a mechanism of tumor promotion.
Recent evidence supports the concept that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis. This study tested the hypothesis that a common property shared by known or suspected tumor promoters is the ability to block the process of apoptosis. A total of 10 tumor promoters were tested and all were found to inhibit DNA fragmentation and cell death of 7 different cell lines triggered into apoptosis by diverse agents. Resistance to apoptosis could be induced rapidly (within 1 h) by treating with relatively high concentrations of promoters. However, low physiological concentrations of promoters could also induce complete resistance to apoptosis after prolonged exposure (5-15 days of culture). Like tumor promotion in vivo, promoter-induced resistance to apoptosis was reversible after culturing in the absence of promoter. These findings provide new insight into the mechanism of tumor promotion and suggest a novel in vitro screening assay to detect new tumor-promoting agents in the environment.
Wright
S C
SC
Palo Alto Institute of Molecular Medicine, Mountain View, California 94043.
Zhong
J
J
Larrick
J W
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002273:Carcinogens / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D007941:Leukemia P388; D015473:Leukemia, Promyelocytic, Acute; D016403:Lymphoma, Large B-Cell, Diffuse; D051379:Mice; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D012439:Saccharin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D002273:Carcinogens; D004054:Diethylstilbestrol; D003634:DDT; D012439:Saccharin; D013755:Tetradecanoylphorbol Acetate