Prof. Zhang Xiaokun: NSAID Sulindac and Its Analog Bind RXRα and Inhibit RXRα-Dependent AKT Signaling

2010.06.14, ProfessorZhang Xiaokun published a paper entitled: “NSAID Sulindac and Its Analog Bind RXRα and Inhibit RXRα-Dependent AKT Signaling” onCancer Cell

Author：Zhou Hu, Liu Wen, Su Ying, Huang Peiqiang, Zhang Xiaokun.etc

Abstract:

Our results demonstrate that RXRα mediates NSAID Sulindac-induced apoptosis. We provide evidence that tRXRα detected in cancer cells acts nongenomically to activate the PI3K/AKT pathway and promote cancer cell growth and survival, which is inhibited by Sulindac. Our finding that Sulindac and TNFα synergistically induce apoptosis through activation of TNFα-dependent apoptotic pathway offers therapeutic strategies to sensitize cancer cells to the killing effect of this cytokine. Our characterizations of RXR-selective Sulindac analog K-80003 demonstrate that Sulindac's anticancer effects can be dissociated from its COX inhibition and identify a RXRα-based lead for cancer therapy. These findings should appeal to a broad audience of clinicians, cancer biologists, molecular biologists, and drug designers.

DOI: http://dx.doi.org/10.1016/j.ccr.2010.04.023

http://pharm.xmu.edu.cn/00/44/c6025a131140/page.htm