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Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells
Author(s) -
Jaiswal Aruna S.,
Narayan Satya
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20156
Subject(s) - adenomatous polyposis coli , cell cycle , cell cycle checkpoint , colorectal cancer , cell growth , cancer research , biology , wild type , microbiology and biotechnology , cancer , chemistry , gene , mutant , biochemistry , genetics
In the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild‐type adenomatous polyposis coli (APC) protein at the post‐translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT‐116 cells (which express the wild‐type APC gene) after treatment with ZnCl 2 . Increased levels of wild‐type but not truncated APC proteins were required for the ZnCl 2 ‐mediated G 2 /M phase arrest in different colon cancer cell lines. We further tested whether serum‐stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl 2 ‐induced G 2 /M phase arrest of HCT‐116 cells. Results showed that in the HCT‐116 cells pretreated with ZnCl 2 , the serum‐stimulation neither changed the distribution of G 2 /M phase arrested cells nor the increased levels of APC protein. The G 2 /M phase arrest correlated with retarded growth of HCT‐116 cells. To further establish that wild‐type APC protein plays a role in ZnCl 2 ‐induced G 2 /M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl 2 treatment did not induce G 2 /M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E‐cadherin and α‐tubulin levels. These results suggest that ZnCl 2 inhibits the proliferation of colon cancer cells (which carry the wild‐type APC gene) through stabilization of the APC protein and cell cycle arrest in the G 2 /M phase. On the other hand, ZnCl 2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability. © 2004 Wiley‐Liss, Inc.