Abstract 1269: Diosgenin, a naturally occurring steroidal saponin, prevents colon cancer in animal models of hereditary and sporadic CRC
Authors: Venkateshwar Madka, Jayadev Raju, Gopal Pathuri, Snigdha Smriti, Anh Bao, Yuting Zhang, Nicole Stratton, Mudassir Farooqui, Stanley Lightfoot, Adam S. Asch, Chinthalapally V. Rao
Journal: Cancer Research (2018)

Abstract Colorectal Cancer (CRC) affects more than 1.35 million people worldwide annually. In the US it is anticipated ~140,000 new cases and 50,000 deaths for the year 2017. In spite of existing preventive measures, recent data suggest an increase in the number of CRC incidences in the younger age groups (30 to 55 years) urging the need for better preventives. In the present study we have studied, Diosgenin against colon cancer in APCmin/+ mice and azoxymethane (AOM)-induced rat CRC models. Diosgenin is a steroid saponin with proven diverse medicinal properties, including anti-diabetic, antiobesity and antiinflammatory, and anticancer properties. APCmin/+ mice, a hereditary polyposis mouse model, were bred in-house and starting at 6 weeks age they were given AIN7-6A diets containing diosgenin (0, 500 and 1,000 ppm) for 14 weeks. At 20-wks of age all mice were euthanized and intestines, both small and large, were analyzed for tumors. In the sporadic CRC model, colon tumors were induced in the male F344 rats by two weekly s.c. injections of AOM (15mg/kg BW) followed by diosgenin administration (0 and 1,000ppm) for 38 weeks. Dietary diosgenin showed significant suppression of colon tumor incidence and multiplicity in both models. In APCmin/+ mice both small intestinal polyps (SIP) and colon tumors (CT) were suppressed in a dose-dependent manner with a significant effect in the high-dose treatment. Diosgenin administered female mice had 33% (25±4.1; Mean±SE, p&amp;lt;0.044) and 54% (17.1+3.8; p&amp;lt;0.003) inhibition of SIP as compared to control mice (37.3±5.6); in male mice there was a greater inhibitory effect (p&amp;lt;0.0001) with 53% (14.1±1.8;) and 65% (10.7±1.7; p&amp;lt;0.0001) suppression of the SIP at 500 and 1,000 ppm respectively, as compared to control mice (30.4±2.3). Colon tumor multiplicity was also inhibited by 65% (0.45±0.24; p&amp;lt;0.05) and 50% (0.5±0.18; p&amp;gt;0.05) with high dose in both male and female mice as compared to their respective controls (1.3±0.20 and 1.0±0.25). Importantly, diosgenin showed a similar inhibitory effect on AOM-induced colon adenocarcinoma incidence and multiplicity in the rat model. Administration of diosgenin significantly suppressed both invasive and non-invasive colon adenocarcinoma incidence by 60% (p&amp;lt;0.005) and multiplicity by 65 % (p&amp;lt;0.0001). HPLC analysis of the intestinal contents of diosgenin suggested that more than 50% reached the colon in its active form. Biomarker analysis suggested that the strong chemopreventive effects are due to the suppression of proliferation (PCNA) and pro-inflammatory proteins (COX-2 and iNOS) with an increase in apoptosis (Casp-3). Based on these results from the preclinical models representing both hereditary and sporadic CRC patients, it is highly imperative to conclude that diosgenin is a potential chemopreventive agent for colon cancer prevention which needs to be further investigated in the clinic. (Endowed Chair Funds from CVR/ASA) Citation Format: Venkateshwar Madka, Jayadev Raju, Gopal Pathuri, Snigdha Smriti, Anh Bao, Yuting Zhang, Nicole Stratton, Mudassir Farooqui, Stanley Lightfoot, Adam S. Asch, Chinthalapally V. Rao. Diosgenin, a naturally occurring steroidal saponin, prevents colon cancer in animal models of hereditary and sporadic CRC [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 1269.