Submitted to: Carcinogenesis
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/27/2004
Publication Date: 1/15/2005
Citation: Ellington, A.A., Berhow, M., Singletary, K.W. 2005. Induction of macroautophagy in human colon cancer cells by B-group soybean saponins. Carcinogenesis. 26:159-167. Interpretive Summary: Diets high in soybean products have been shown to lower the risk for getting certain chronic diseases such as cancer. The actual agents in soy that prevent these diseases have not yet been accurately determined. Soy contains a number of biologically active "nutriceuticals" which have not been examined for biological activity in human systems. One such group of nutriceuticals are the soy saponins. It was found in that treatment of cultured human colon cancer cells with soy saponin at levels found in a soy rich diet caused the cancer cells to go into a programmed "cell death." This indicates that diets rich in soy saponins may be able to slow or stop colon cancer development. Further work is needed to fully evaluate this observation.
Technical 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 B-group soybean 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-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 macro autophagy, 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 potentially induce macro autophagy, 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.