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Carcinogenesis Advance Access published online on October 7, 2004
Carcinogenesis, doi:10.1093/carcin/bgh297
© 2004 by Oxford University Press
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Received July 2, 2004
Revised August 26, 2004
Accepted September 27, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins

Allison A. Ellington 1, Mark Berhow 1, and Keith W. Singletary 2*

1 National Center for Agricultural Research Service, Peoria, IL
2 Department of Food Science and Human Nutrition, 905 South Goodwin Ave, 467 Bevier Hall, Urbana, IL, 61801

* To whom correspondence should be addressed. E-mail: kws{at}uiuc.edu.


  Abstract

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 ppm significantly reduced viable cell numbers after 24 and 48 hours of exposure. Treatment of cells with 25 and 100 ppm 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 approximate 4.5-fold increase in cell morphologies characteristic of Type II nonapoptotic 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.

Keywords: soyasaponins; macroautophagy; colon cancer; S-phase; diet.
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