Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway

作者：Zheng, Xiufeng; Wu, Jinrong; Shao, Qun; Li, Xuesong; Kou, Jiayuan; Zhu, Xing; Zhong, Zhaoyu; Jiang, Yueqing; Liu, Zhongni; Li, Hongxia; Tian, Ye^*; Yang, Liming^*

来源：Cellular Physiology and Biochemistry, 2016, 38(2): 545-557.

DOI：10.1159/000438649

• Pseudohypericin
• Sonodynamic therapy
• Apoptosis
• THP-1 macrophages
• Mitochondriacaspase pathway

Background/Aims: Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY-SDT on THP-1 macrophages. Methods: THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Delta Psi m) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins. Results: P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and Delta Psi m loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC). Conclusion: P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening. 2016 The Author(s) Published by S. Karger AG, Basel

• 出版日期2016
• 单位哈尔滨医科大学