Abstract 5563: The anti-cancer and anti-hyperlipidemia effects of triterpenoids from Gynostemma pentaphyllum in the Apcmin/+ mouse model

Abstract

Abstract Apcmin/+ mice, a commonly used mouse model for colorectal cancer, manifest both high number of intestinal polyps and hyperlipidemia, which make the min/+ mouse an ideal animal model for drug intervention studies for both hyperlipidemia and colorectal cancer Triterpenoids, produced in many plants, are widely used in Asian medicine. Gynostemma pentaphyllum (Gp), also called jiaogulan, is a rich source of dammarane-type triterpenoids and is used as a traditional Chinese herbal medicine for the treatment of various diseases including cancer and hyperlipidemia. However, the proven efficacy and the underlying mechanism have not been investigated systematically. Using the Apcmin/+ mouse as the animal model, treatment with Gp total triterpenoids (GpMix) markedly reduce the numbers and sizes of polyps. In conjunction with 5-fluorouracil (5-FU), the size and numbers of polyps of the treated animals were further reduced. Besides the anti-cancer effect of GpMix, we have also shown that the GpMix can effectively suppress the plasma triglycerides and cholesterol levels in Apcmin/+ mice. To delineate the precise mechanisms of the anti-cancer and anti-hyperlipidemia effects of GpMix, we performed molecular and proteomic analysis of the plasma obtained from animals treated with and without GpMix. Results showed that lipoprotein lipase, PPARα and adiponectin are upregulated and HMG-CoA reductase is down-regulated upon GpMix treatment. Plasma protein profiling revealed that several downregulated proteins are directly related to cancer, inflammatory, cell proliferation, including serum amyloid A1 and A2, serum amyloid P-component, major urinary proteins, glutathione peroxidase 3, complement C3 and serotransferrin. In the same treated animals, four lipogenesis proteins including apolipoprotein A-I, apolipoprotein A-II, apolipoprotein A-IV, and apolipoprotein C-III by which the activity of lipoprotein lipase is tightly regulated are downregulated. These protein profiling data, together with the adipocyte-specific signaling data shown above provide solid evidence of the anti-cancer and anti-hyperlipidemia effects of GpMix. [This study was financially supported by Research Grants Council of Hong Kong under HKBU2/07C and FRG/07-08/II-50 and FRG/08-09/II-61 Grants to WLWH.] Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5563.