NSAID Sulindac and Its Analog Bind RXRα and Inhibit RXRα-Dependent AKT Signaling

Citations of this article
Mendeley users who have this article in their library.


Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-α (RXRα). We identified an N-terminally truncated RXRα (tRXRα) in several cancer cell lines and primary tumors, which interacted with the p85α subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-α (TNFα) promoted tRXRα interaction with the p85α, activating PI3K/AKT signaling. When combined with TNFα, Sulindac inhibited TNFα-induced tRXRα/p85α interaction, leading to activation of the death receptor-mediated apoptotic pathway. We designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXRα but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXRα-dependent AKT activation and tRXRα tumor growth in animals. © 2010 Elsevier Inc. All rights reserved.

Author supplied keywords




Zhou, H., Liu, W., Su, Y., Wei, Z., Liu, J., Kolluri, S. K., … Zhang, X. K. (2010). NSAID Sulindac and Its Analog Bind RXRα and Inhibit RXRα-Dependent AKT Signaling. Cancer Cell, 17(6), 560–573. https://doi.org/10.1016/j.ccr.2010.04.023

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free