Curcumin Induces Human Colon Cancer Cell death via p62/SQSTM1 Degradation, Phospho-ERK Up-regulation and Ceramide Generation

Order of Publishing in Issue: 
3
Volume :6
Issue :4
October, 2012
Page No: 
407-417
Authors: 
Mahendra Patel, Faisal Thayyullathil, Shahanas Chathoth, Abdulkader Hago, Siraj Pallichankandy, Anees Rahman and Sehamuddin Galadari*
Address: 
Mahendra Patel, Faisal Thayyullathil, Shahanas Chathoth, Abdulkader Hago, Siraj Pallichankandy, Anees Rahman and Sehamuddin Galadari*
Email-ID: 
sehamuddin@uaeu.ac.ae

Abstract

Curcumin is a natural yellow phenolic compound extracted from the Indian spice, turmeric (Curcuma longa). Several studies demonstrated the ability of curcumin to inhibit events associated with the promotion of cancer. We investigated the effects curcumin on human colon cancer cells in vitro and further examined the molecular mechanisms of curcumin induced cell death. The signaling adapter p62/SQSTM1, a multifunctional protein implicated in autophagy, apoptosis, cell signaling pathways and tumorigenesis, is one of the potential targets for anti-cancer therapy. In this study, we demonstrate a dose and time-dependent down-regulation of p62/SQSTM1 expression by curcumin that correlates with increase in the loss of viability of human colon cancer cells. We also found that curcumin enhanced phospho-ERK expression and ceramide (Cer) generation in human colon cancer cells. However, the present study also shows that, curcumin-induced p62/SQSTM1 degradation, up-regulation of ERK phosphorylation, Cer generation and cell death can be reversed by extracellular anti-oxidants such as glutathione (GSH) and N-acetyl cysteine (NAC). Overall, our results suggest that down regulation of p62/SQSTM1 and up-regulation of phospho-ERK and Cer generation may contribute to the anti-proliferative effects of curcumin against human colon cancer cells.

Keywords: 
p62/SQSTM1, phospho-ERK, Curcumin, Ceramide, Apoptosis, GSH
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