Carcinogenesis Advance Access originally published online on August 19, 2005
Carcinogenesis 2006 27(2):298-306; doi:10.1093/carcin/bgi214
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis Vol.27 no.2 © Oxford University Press 2005; all rights reserved.
Inhibition of Akt signaling and enhanced ERK1/2 activity are involved in induction of macroautophagy by triterpenoid B-group soyasaponins in colon cancer cells
Department of Food Science and Human Nutrition, University of Illinois, 905 South Goodwin Avenue, Bevier Hall, Urbana, IL 61801, USA and 1 National Center for Agricultural Research Service, Peoria, IL 61601, USA
* To whom correspondence should be addressed. Tel: +1 217 333 5549; Fax: +1 217 265 0925; Email: kws{at}uiuc.edu
Triterpenoid B-group soyasaponins have been found to induce macroautophagy in human colon cancer cells at concentrations obtainable through consumption of legume foodstuffs. In the present studies the mechanism(s) for this autophagy-inducing action of soyasaponins was evaluated by measuring changes in signal transduction pathways associated with autophagy. Specifically, inhibition of the Akt signaling pathway and enhanced activity of ERK1/2 have previously been implicated in controlling induction of macroautophagy in mammalian cancer cells. Here we show that these pathways are also involved in B-group soyasaponin-induced macroautophagy, as changes in enzyme activities preceded significant increases in autophagic activity. The autophagic capacity of HCT-15 cells was significantly increased by 6 h post-saponin exposure, which led us to measure alterations in signaling events that preceded this time point. We determined that exposure to B-group soyasaponins suppressed Akt activity maximally by 50%, which was associated with a reduction in the activating phosphorylation of the Akt-serine473 residue. In addition, ERK1/2 activity was significantly increased by 60%, and was determined to be necessary for B-group soyasaponin-induced autophagy. The raf-1 kinase has been identified as a potential point of cross-talk between the Akt and ERK1/2 signaling cascades. Following B-group soyasaponin treatment activity of raf-1 was significantly increased by a maximal 200%, suggesting that this enzyme in part modulates the enhanced ERK1/2 activity. These results provide new insights into the signaling events that control induction of autophagy by B-group soyasaponins in human colon cancer cells and suggest that soyasaponins warrant further study as potential colon cancer chemopreventive agents.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Bartholomeusz, D. Rosen, C. Wei, A. Kazansky, F. Yamasaki, T. Takahashi, H. Itamochi, S. Kondo, J. Liu, and N. T. Ueno PEA-15 Induces Autophagy in Human Ovarian Cancer Cells and Is Associated with Prolonged Overall Survival Cancer Res., November 15, 2008; 68(22): 9302 - 9310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Singletary and J. Milner Diet, Autophagy, and Cancer: A Review Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1596 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kovsan, R. Ben-Romano, S. C. Souza, A. S. Greenberg, and A. Rudich Regulation of Adipocyte Lipolysis by Degradation of the Perilipin Protein: NELFINAVIR ENHANCES LYSOSOME-MEDIATED PERILIPIN PROTEOLYSIS J. Biol. Chem., July 27, 2007; 282(30): 21704 - 21711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aoki, Y. Takada, S. Kondo, R. Sawaya, B. B. Aggarwal, and Y. Kondo Evidence That Curcumin Suppresses the Growth of Malignant Gliomas in Vitro and in Vivo through Induction of Autophagy: Role of Akt and Extracellular Signal-Regulated Kinase Signaling Pathways Mol. Pharmacol., July 1, 2007; 72(1): 29 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M.Y. Tin, C.-H. Cho, K. Chan, A. E. James, and J. K.S. Ko Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft Carcinogenesis, June 1, 2007; 28(6): 1347 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Minsavage and J. F. Dillman III Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor {kappa}B Responses and Cell Death Are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 202 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-h. Zhu, C. Horbinski, F. Guo, S. Watkins, Y. Uchiyama, and C. T. Chu Regulation of Autophagy by Extracellular Signal-Regulated Protein Kinases During 1-Methyl-4-Phenylpyridinium-Induced Cell Death Am. J. Pathol., January 1, 2007; 170(1): 75 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-L. Kuo, Y.-L. Hsu, and C.-Y. Cho Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells Mol. Cancer Ther., December 1, 2006; 5(12): 3209 - 3221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Herman-Antosiewicz, D. E. Johnson, and S. V. Singh Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome c and Apoptosis in Human Prostate Cancer Cells Cancer Res., June 1, 2006; 66(11): 5828 - 5835. [Abstract] [Full Text] [PDF]
|
|