Abstract 2884: Resveratrol, a red wine polyphenol, suppresses pancreatic cancer by inhibiting leukotriene A4 hydrolase

Abstract

Abstract Considerable attention has focused on the anticancer effects of red wine. Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a well-known polyphenolic compound found in red wine and recognized as a key substance for cancer chemoprevention. Leukotriene A4 hydrolase (LTA4H) is a bi-functional zinc enzyme that is regarded as a relevant target in certain types of human cancers. Our data indicate that knockdown of LTA4H decreased production of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of MIA PaCa-2 pancreatic cancer cells. An in silico prediction using a shape-similarity approach suggested that LTA4H might be a potential target of resveratrol. Results showed that resveratrol directly bound to LTA4H in vitro and ex vivo and suppressed proliferation and anchorage-independent growth by inhibiting LTA4H activity in MIA PaCa-2 cells. Importantly, resveratrol exerted stronger inhibitory effects compared to bestatin, a well-known inhibitor of LTA4H activity. The inhibitory effects of resveratrol were reduced in MIA PaCa-2 cells transfected with sh-LTA4H compared with sh-mock transfected cells. Notably, in an in vivo xenograft mouse model, resveratrol suppressed MIA PaCa-2 tumor formation by inhibiting LTA4H activity. These findings suggest that LTA4H is a novel target for the preventive and/or therapeutic effects of resveratrol on pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2884. doi:10.1158/1538-7445.AM2011-2884