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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #231588
Title: Deoxycholic Acid and Selenium Metabolite Methylselenol Exert Common and Distinct Effects on Cell Cycle, Apoptosis, and MAP Kinase Pathway in HCT116 Human Colon Cancer Cells

Author
item Zeng, Huawei
item Botnen, James
item Briske Anderson, Mary

Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/4/2009
Publication Date: 1/10/2010
Citation: Zeng, H., Botnen, J.H., Briske Anderson, M.J. 2010. Deoxycholic Acid and Selenium Metabolite Methylselenol Exert Common and Distinct Effects on Cell Cycle, Apoptosis, and MAP Kinase Pathway in HCT116 Human Colon Cancer Cells. Nutrition and Cancer. 62(1):85-92.

Interpretive Summary: A typical part of the Western diet is a high fat intake that leads to increased levels of fecal bile acids, and these bile acids, primarily deoxycholic acid (DCA) in humans, have been believed to be tumor promoters of colon cancer. There is increasing evidence suggests that they may exert their tumor promoting activity by modulating cellular signaling and gene expression, which ultimately alters colon cell proliferation. It has been suggested that cell growth inhibition induced by DCA may cause compensatory hyperproliferation of a subpopulation of colonic epithelial cells resistant to DCA’s inhibitory effect (4). These surviving cells are somehow mutated and are resistant to the bile acid- induced cell cycle arrest and apoptosis, and consequently increase cancer risk. However, the mechanism by which DCA and other bile acids promote colon tumorigenesis remains to be characterized. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as cancer-chemopreventive compounds. Methylselenol has been hypothesized to be a critical selenium metabolite for anticancer activity in vivo. In this study, we demonstrated that methylselenol may have the potential to inhibit the growth of DCA-resistant colon cells via its unique molecular targets. The information will be useful information for scientists and health-care professionals who are interested in nutrition and cancer prevention.

Technical Abstract: Bile acid deoxycholic acid (DCA) is a known tumor promoter in colon tumor development. The cell growth inhibition induced by DCA may cause compensatory hyperproliferation of colonic epithelial cells and provide selection for subpopulations of cells resistant to DCA’s inhibitory effect. These surviving cells are somehow mutated and are resistant to the bile acid, and consequently increase cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as cancer-chemopreventive compounds. Methylselenol has been hypothesized to be a critical selenium metabolite for anticancer activity in vivo. In this study, we demonstrated that, both 75 - 300 µmol/L DCA and methylselenol generated by incubating 40 U/L METase with 1.25 - 5 µmol/L SeMet, inhibited colon cancer cell proliferation by up to 64%. Cell cycle analyses revealed that DCA induced an increase in only G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA but not methylselenol induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data suggest that methylselenol may have the potential to inhibit the growth of DCA-resistant colon cells via its unique molecular targets.