Abstract 5384: Tanshinone IIA synergizes with arsenic trioxide to promote human NB4 promyelocytic leukemia cell differentiation and apoptosis

Background: Tanshinone IIA (TIIA), a natural compound isolated from Salvia Miltiorrhiza, has been used for hematological malignancies as an adjunctive therapy in combination with arsenic in other countries. However, the molecular mechanism of TIIA as an adjunctive therapy has not been well documented. The goal of this study is to develop novel strategies to treat human promyelocytic leukemia. Methods: Purified TIIA was used for this pilot study; and purified arsenic trioxide (ATO) was purchased from Sigma. Western blotting and flow cytometry were employed to evaluate biomarker expression in human NB4 promyelocytic leukemia cells prior to treatment and 2-5 days after treatment. Results: TIIA induced NB4 cell apoptosis at the concentrations above 0.75 µM, a concentration that is below plasma concentrations that can be achieved in vivo. TIIA was not toxic to peripheral blood mononuclear cells (PBMC) from healthy individuals at 3 µM, the highest concentration tested. TIIA also promoted NB4 differentiation at and above 0.75 µM. TIIA up-regulated the percentage of CD11b+ NB4 cells, as well as increasing the percentage of NBT+ cells. In addition, There were not significant differences between TIIA (1µM) and ATRA (1 µM), in terms of their impact on NB4 cell differentiation, as assessed by NBT and CD11b assays. TIIA also inhibited NB4 cell colony formation in CFU-L assays. Western blotting demonstrated that TIIA down-regulated c-Myc expression in NB4 cells. The combination of ATO and TIIA increased NB4 cell death when compared with single drug treatment (TIIA or ATO). In addition, the combination of TIIA and ATO had stronger impact on the induction of NB4 cell differentiation, as assessed by CD11b expression. Conclusion: TIIA is a potential novel adjunctive agent to be considered in combination with ATO for the treatment of human promyelocytic leukemia. 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 5384.