Joseph, Jeena and Wajapeyee, Narendra and Somasundaram, Kumaravel (2005) Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate. In: International Journal of Cancer, 115 (1). pp. 11-18.
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Histone deacetylases inhibitors (HDIs) induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, has been shown to cause a G(1) cell cycle arrest by inducing p21(WAF1/CIP1) in a p53-independent manner. In this report, we present evidence for activation of p53 pathway by NaBand its role in the NaB-mediated growth suppression. Addition of NaB increased the levels of p53 involving a p14(ARF)-dependent post-transcriptional mechanism. NaB induced p53 is functional as it activated p53-specific reporter, induced the level of p21(WAF1/CIP1),inhibited cellular DNA synthesis and induced apoptosis. By using HPV 16E6 stable transfectants as well as p53 null cancer cells, we show that NaB suppresses the growth of WT p53 containing cells more efficiently.NaB inhibited DNA synthesis to similar extent both in the presence and absence of p53. However, NaB treatment lead to a major G(2)/M arrest of cells in the presence of p53, while cells without wild-type p53 accumulated mainly in G, phase of the cell cycle. Furthermore,apoptosis induction by NaB is greatly reduced in the absence of p53.These results suggest that p53 pathway mediates in part growth suppression by NaB and the p53 status may be an important determinant of chemosensitivity in HDI based cancer chemotherapy.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to John Wiley and Sons.|
|Keywords:||Histone deacetylase inhibitors;sodium butyrate;p53;apoptosis;growth arrest|
|Department/Centre:||Division of Biological Sciences > Microbiology & Cell Biology|
|Date Deposited:||08 Jun 2005|
|Last Modified:||25 Jan 2012 10:15|
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