The in vitro Investigation of Tanshinone IIA on Mitochondria and the Axis of Autophagy-Inflammation-Apoptosis

Danshen is a common herb, which was widely used in traditional Chinese medicine for clearing the heat and extinguishes blood stasis. Tanshinone IIA (Tan IIA) is the main compound in Danshen. Tan IIA is a derivative of phenanthrene-quinone. It has antioxidant, antibacterial, anti-inflammatory, anti-immunological, anti-allergic, and anti-tumor properties. Tan IIA is common used for anticancer and anti-inflammation in our clinical application. Apoptosis and inflammation are highly associated with mitochondrial function. In our previous report, we found that Tan IIA exerted dual function to induce apoptosis in cancer cells and inhibit inflammation on endothelial cells. Therefore, Mitochondria might play a major role in complex physiological and pathological processes of the preceding biological function induced by Tan IIA. Autophagy can cause degenerative diseases in which deficient quality control results in inflammation and cell death. The autophagy-inflammation-apoptosis axis may directly or indirectly implicate mitochondrial dynamics and morphological change. In this study, we try to figure out the protective or damage effect provided by Tan IIA through activation of mitochondrial survival/nonsurvival signaling pathway in cancer cells and endothelial cells including enhancement of mitochondrial dynamic balance and induction of mitochondrial autophagy. We will focus on the roles of mitochondria in cancer cells (143B) and endothelial cells (HUVEC) affected by Tan IIA. Initially, we will exam whether Tan IIA will trigger intracellular and mitochondrial ROS production, mitochondrial membrane potential and mitochondrial function including ATP production, O2 consumption and respiratory chain reaction of these two cell lines. In the mean time, the mitochondrial fusion and fission proteins including Mfn1, Mfn2 OPA1, hFis-1 and Drp1 and morphological changes during the course of autophagy-inflammation-apoptosis in response to Tan IIA will be determined. In addition, we will check up what the differences of cell survival (autophagy) or non-survival (apoptosis) mechanism associated with mitochondrial dynamic balance and induction of mitochondrial autophagy in response to Tan IIA between 143B and HUVEC cells. Altogether, we hypothesize that Tan IIA may play an important and different role in regulation of dynamics and organization of mitochondria that are dependent on their different cell characteristics. We are conducting this project to comprehensively study Tan IIA on cancer and endothelial cells associated with mitochondria, which may hopefully provide the evidences before we enter clinical trial. We also anticipate that it may provide clues in future treatment of this compound into clinical application.

Project ID:PC10207-0330
External Project ID:NSC102-2320-B182-016