Abstract 2249: Induction of PIAS3 by curcumin as a novel treatment strategy in mesothelioma.

Abstract

Abstract Curcumin, a natural drug derived from the spice turmeric, has been extensively studied as an anti-cancer agent. The mechanism of action behind this promising bioactivity of curcumin, previously unclear, is now beginning to emerge. Curcumin has been shown to inhibit STAT3 phosphorylation and activity in melanoma cells, ovarian and endometrial cancer cells and small-cell lung cancer cells. In many cancers constitutively activated STAT3 (Signal Transducers and Activators of Transcription 3) is essential for cell proliferation. In this study we demonstrate that four mesothelioma cell lines demonstrate high levels of active STAT3. The addition of curcumin can suppress mesothelioma cell growth and proliferation, demonstrating the STAT3-dependence of these cells. Interestingly, the inhibitory effect of curcumin on STAT3 appears to be mediated through an upregulation of an endogenous inhibitor of STAT3 called PIAS3 (protein inhibitor of activated STAT3). Thus, the significance of our results is that curcumin not only targets an effector of mesothelioma cell proliferation, STAT3, but does this by increasing the expression of its endogenous inhibitor, PIAS3. This result prompted ongoing studies to determine if PIAS3 levels are deficient in mesothelioma tumor specimens obtained from the National Virtual Mesothelioma bank. Taken together, our data support the idea that mesothelioma is a STAT3-driven cancer caused by a lack of PIAS3 expression and that strategies to increase endogenous PIAS3 expression will have tumor suppressor effects. The ability of curcumin to increase PIAS3 expression will give us a jump start on pursuing this strategy because it represents a bioactive lead compound with many available structural analogs. Citation Format: Snehal Dabir, Gary Wildey, Afshin Dowlati. Induction of PIAS3 by curcumin as a novel treatment strategy in mesothelioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2249. doi:10.1158/1538-7445.AM2013-2249