Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins.
The impact of triterpenoid saponins isolated from soybeans on suppression of colon cancer cell proliferation was evaluated. Experiments were conducted to determine the effects of a purified soybean B-group saponin extract on cell proliferation, cell-cycle distribution and programmed cell death in cultures of human HCT-15 colon adenocarcinoma cells. Treatment of cells with the soyasaponins at concentrations of 25-500 p.p.m. significantly reduced viable cell numbers after 24 and 48 h of exposure. Treatment of cells with 25 and 100 p.p.m. of saponins also resulted in a transient accumulation of cells in the S-phase of the cell cycle that was associated with a significant reduction of cyclin-dependant kinase-2 (CDK-2) activity. More striking was that, when examined by transmission electron microscopy, soyasaponin-treated cells exhibited an approximately 4.5-fold increase in cell morphologies characteristic of Type II non-apoptotic programmed cell death (PCD) including numerous autophagic vacuoles, changes that collectively suggest autophagic cell death. In addition, the protein levels of microtubule-associated protein light chain 3 (LC-3), a specific marker of macroautophagy, increased substantially following soyasaponin treatment. Taken together these results thus indicate that soybean saponins, at physiologically relevant doses, can suppress HCT-15 colon cancer cell proliferation through S-phase cell-cycle delay, and can induce macroautophagy, the hallmark of Type II PCD. These findings suggest that B-group soyasaponins may be another colon-cancer suppressive component of soy that warrants further examination as a potential chemopreventive phytochemical.
Ellington
Allison A
AA
Department of Food Science and Human Nutrition, 905 South Goodwin Avenue, 467 Bevier Hall, Urbana, IL 61801, USA.
Berhow
Mark
M
Singletary
Keith W
KW
D000230:Adenocarcinoma / Q000473:pathology* / Q000648:ultrastructure; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D046529:Microscopy, Electron, Transmission; D012503:Saponins / Q000494:pharmacology*; D030262:Soybean Proteins / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry
D012503:Saponins; D030262:Soybean Proteins