Abstract 4984: Celastrol inhibits high fat diet-induced obesity and intestinal tumorigenesis in APCMin/+mice by modulating gut microbes and inflammation

Obesity and inflammation play a vital role in colorectal cancer (CRC). Antiobesity agents may be beneficial for CRC prevention. Celastrol is a triterpene bioactive compound derived from Tripterygium wilfordii (TW) plant, which possesses antiobesity and anti-inflammatory properties. In the present study, we tested celastrol for its intestinal tumor inhibitory efficacy, modulation of intestinal microbiome, induction of UCP-1 in inguinal fat, and inflammation under obese conditions using APC Min/+ mouse model. For efficacy study, six-week-old male and female C57BL/6J-APC Min/+ mice (10 mice/group/gender) were fed high-fat diets (HFD; 60% Kcal fat) containing 0 and 150 ppm celastrol and a group of mice with a low-fat diet (LFD; 10% Kca fat) for 11 weeks. At termination, intestinal tumors were evaluated histologically and serum was assayed for fasting glucose, uric acid, liver enzymes (ALT, AST), triglycerides and cholesterol levels. Untreated and treated intestinal tumors were assayed for apoptosis and inflammatory markers by real-time PCR method. Results suggest that administration of LFD showed lower intestinal tumor formation by 52% (p Min/+ mice. Stephenson Cancer Center Grant. Citation Format: Naveena B. Janakiram, Venkateshwar Madka, Yuting Zhang, Nicole Stratton, Hima Bezawada, Beth Griesel, Altaf Mohammed, Ann L. Olson, Chinthalapally V. Rao. Celastrol inhibits high fat diet-induced obesity and intestinal tumorigenesis in APC Min/+ mice by modulating gut microbes and inflammation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4984.