Journal Article

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

Allison A. Ellington, Mark Berhow and Keith W. Singletary

in Carcinogenesis

Volume 26, issue 1, pages 159-167
Published in print January 2005 | ISSN: 0143-3334
Published online January 2005 | e-ISSN: 1460-2180 | DOI:
Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins

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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.

Keywords: AVi, immature, non-degradative autophagic vacuoles; AVd, mature, degradative autophagic vacuoles; CDK-2, cyclin-dependant kinase 2; CDKI, cyclin-dependent kinase inhibitor; LC-3, microtubule-associated protein light chain 3; 3-MA, 3-methyladenine; MDC, monodansylcadaverine; PCD, programmed cell death

Journal Article.  5933 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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