Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb/c mice.

Abstract

It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo. In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells. The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis. Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c-Myc, E2F1 and Phos p38 MAP kinase. Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase in mouse colon cancer MC26 cells. When the MC26 cells were transplanted to their immune-competent Balb/c mice, methylselenol-treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells. Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth.

• Authors: Huawei Zeng, Wen-Hsing Cheng, Luann K Johnson
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 24 Issue 5 Pg. 776-80 (May 2013) ISSN: 1873-4847 [Electronic] United States
• PMID: 22841391 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013. Published by Elsevier Inc.

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Organoselenium Compounds
• Tumor Suppressor Protein p53
• methaneselenol
• p38 Mitogen-Activated Protein Kinases
• Methanol

Topics

• Animals
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, genetics, pathology)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• G1 Phase (drug effects)
• G2 Phase (drug effects)
• HCT116 Cells
• Humans
• Male
• Methanol (analogs & derivatives, pharmacology)
• Mice
• Mice, Inbred BALB C
• Organoselenium Compounds (pharmacology)
• S Phase (drug effects)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Xenograft Model Antitumor Assays
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)