Abstract 1630: Vitamin E delta-tocotrienol prevents azoxymethane-induced colon carcinogenesis progression in Fisher-344 rats

Abstract

Abstract Background: Chemoprevention by bioactive food components has emerged as an alternative approach for the prevention of colorectal carcinogenesis. We have shown that natural vitamin E delta-tocotrienol is the most bioactive tocotrienol against pancreatic cancer. This study evaluated the efficacy of vitamin E delta-tocotrienol feeding in the prevention of azoxymethane-induced colorectal polyps and cancer formation in Fisher-344 rats. We also evaluated the antitumor activity of vitamin E delta-tocotrienol in colorectal cancer cell lines and in APCmin mouse model. Methods: The in vivo antitumor activity of delta-tocotrienol was evaluated in azoxymethane-treated Fisher-344 rats. Rats were administered azoxymethane (15 mg/kg, SC, 2 x in 2 weeks) then randomly selected into 3 groups: 1) No treatment, 2) Vehicle (ethanol extracted olive oil, 1 ml/kg, PO twice daily and 3) Delta-tocotrienol (200 mg/kg, PO) twice daily for 20 or 40 weeks. The animals were euthanized and the colons were examined for polyps and cancers. Colon tissues were fixed in buffered formalin, embedded, cut and stained with H & E and scored. The APCmin mice were treated with 1) vehicle (olive oil, 1 ml/kg, PO) twice daily for 2 weeks and 2) Delta-tocotrienol (200 mg/kg, PO) twice daily for 2 weeks. Mice euthanized and colon tissues isolated and evaluated for proliferation and apoptosis by immunohistochemistry staining. The in vitro anti-tumor activity of delta-tocotrienol was preformed in human colorectal cancer cell lines HCT-116, HT-29 and SW 480. Results: Delta-tocotrienol feeding to azoxymethane-treated rats significantly reduced (75%, p<0.002) the number of polyps formation compared to untreated or vehicle treated rats. Moreover, the number of colon cancer formation was reduced (70%, p<0.001) with delta-tocotrienol feeding compared to untreated or vehicle treated rats. In colonic tissues of APCmin mice, delta-tocotrienol feeding decreased proliferation (Ki-67), induction of p27, and induction of apoptosis (caspase-3) compared to vehicle treated mice. Delta-tocotrienol also inhibited cell proliferation and induced apoptosis in HCT-116, HT-29 and SW 480 cell lines, through induction of nuclear factor kappa-B (NF-kB) and degradation of beta-catenin. Conclusion: These data show the efficacy of natural vitamin E delta-tocotrienol against the early stages of colorectal carcinogenesis as well as anti-proliferative and apoptotic activity in colorectal cancer both in vitro and in vivo. Delta tocotrienol likely targets NF-kB and beta-catenin signaling pathways, suggesting its potential clinical usefulness for the prevention of human colorectal cancer. 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 1630. doi:1538-7445.AM2012-1630