Abstract 951: Preclinical evaluation of Xanthohumol in carcinoid cancer growth in vitro and in vivo

Abstract

Abstract Background: Besides surgery, there is no potential curative treatment for carcinoid tumors. Because these cancers are metastatic in nature and produce excessive amounts of various bioactive hormones, patients diagnosed with this malignancy will have poor quality of life due to carcinoid syndrome. Therefore, new anticarcinogenic agents are required to improve the effectiveness of treatment. Xanthohumol (XN) (Tetrahydroxy-3′-prenylchalcone) is a prenylated chalconoid found in hops and beer that has been found to have potential anticancer and bioactive properties. Therefore, the purpose of this study was to evaluate the effectiveness of xanthohumol (XN) on carcinoid cancer growth in vitro and in vivo. Methods: To examine the anticancer activity of XN, we treated human gastrointestinal carcinoid BON and bronchopulmonary carcinoid H727 cells with up to 15 μmol/L of XN or carrier (DMSO), and analyzed the effect on cell growth by colony formation assay. The mechanism of growth inhibition was examined by flow cytometry and western analysis for the levels of pro-apoptotic and cell cycle regulatory proteins. To examine the anticancer activity of XN in vivo, subcutaneous BON carcinoid tumors developed in murine xenografts were subjected to intraperitoneal injections of XN (3 mg/kg bwt) or an appropriate volume of DMSO carrier every other day. Results: Treatment with xanthohumol significantly reduced the ability of carcinoid cells to form colonies in a dose-dependent manner. Flow cytometry and western analysis confirmed the observed decrease in cell viability, and showed the decrease was mediated through apoptosis. The carcinoid tumors in the mouse xenograft experiment showed a significant reduction in growth. Conclusions: XN treatment reduced cell viability, colony forming ability and increased cell death through apoptosis. In addition, administration of XN suppressed cancer cell growth in an in vivo xenograft mouse model. Our findings demonstrate for the first time the anti-proliferative effects of xanthohumol in carcinoid cell lines in vivo. Xanthohumol is already being used as a dietary supplement to encourage overall health and has shown few side effects. This fact combined with the potential anticarcinogenic activity found here warrants clinical investigation on patients with carcinoid disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 951. doi:1538-7445.AM2012-951