Carcinogenesis Advance Access originally published online on October 7, 2004
Carcinogenesis 2005 26(1):159-167; doi:10.1093/carcin/bgh297
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Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.
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Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins
1 National Center for Agricultural Research Service, Peoria, Illinois, USA and 2 Department of Food Science and Human Nutrition, 905 South Goodwin Avenue, 467 Bevier Hall, Urbana, IL 61801, USA
3 To whom correspondence should be addressed Email: kws{at}uiuc.edu
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 
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.
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