Abstract 1891: Tanshinone IIA is a novel agent for melanoma prevention and therapy

Background: Tanshinone IIA (TIIA) is a non-toxic natural compound isolated from traditional Chinese herb, Salvia Miltiorrhiza that has been used for prevention and therapy of a wide array of diseases such as vascular diseases and cancers in other countries. It has been documented outside the United States that TIIA has the biological functions of being pro-differentiation, anti-oxidant, anti-inflammation, anti-carcinogenesis and anti-tumor. However, TIIA has not been studied for melanoma prevention and therapy up to date. Methods: Purified standard substance of TIIA has been use for this pilot study. Human adult epidermal melanocyte HEMa-LP and primary human melanoma cell MEL526 were used. Western blot, flow cytometry, ELISA and immunofluorescence techniques were employed to probe the biomarkers interested pre and post treatment of TIIA. Results: TIIA inhibited MEL526 proliferation and induced MEL526 apoptosis at 20 µM that is below far away from TIIA plasma therapeutic concentrations in vivo. TIIA inhibited MEL526 cell motility at concentrations of 2.5µM or 5µM. TIIA (1.25 µM, 2.5 µM and 5 µM) prevented melanocyte epigenetic transdifferentiation to malignant melanoma cell induced by MEL526 conditioned cell culture medium, while TIIA is not toxic to normal melanocytes at those concentrations. TIIA induced transformed-HEMa-LP cell apoptosis at the above concentrations addressed. TIIA consistently down-regulated, at various ratios of drug concentration/cell density, the expression of melanoma stem cell biomarker CD133, and the expression of chondroitin sulfate proteoglycan 4 that is associated positively with melanocytic malignant transformation/progression and melanoma stem cell biomarker expression. STAT5-mediated up-regulation of Foxp3 has been documented in regulatory T cell differentiation and function, but not in melanocyte; and the higher expression level of STAT5a predicts the lower degree of atypia of nevi. In this study it was fund that TIIA increased the expression of STAT5a in MEL526 while the expression of Foxp3, a cancer suppressor gene, was up-regulated. TIIA inhibited the activation EFGR, which activation promotes carcinogenesis and progression of skin cancers. It was not found that TIIA regulated other biomarkers tested such as HLA Class I and B7H1 antigens. In addition, it was found that TIIA promoted human PBMC to produce IFNγ. Conclusion: TIIA is a potential novel agent used for melanoma prevention and therapy. However, further studies of TIIA are needed to prove the biological function and mechanisms in vivo. 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 1891.