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Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway

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Abstract

Betulinic acid (BA), a pentacyclic triterpene of natural origin, has been demonstrated to have varied biologic activities including anti-viral, anti-inflammatory, and anti-malarial effects; it has also been found to induce apoptosis in many types of cancer. However, little is known about the effect of BA on normal cells. In this study, the effects of BA on normal neuronal cell apoptosis and the mechanisms involved were studied using differentiated PC12 cells as a model. Treatment with 50 μM BA for 24 h apparently induced PC12 cell apoptosis. In the early stage of apoptosis, the level of intracellular reactive oxygen species (ROS) increased. Afterwards, the loss of the mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3 occurred. Treatment with antioxidants could significantly reduce BA-induced PC12 cell apoptosis. In conclusion, we report for the first time that BA induced the mitochondrial apoptotic pathway in differentiated PC12 cells through ROS.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 81171147), “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province (No. RC201156), “Six Categories of Key Person” Research Foundation of Jiangsu Province (No. 069), and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. JX10231801).

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    Authors and Affiliations

    1. Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

      Xi Wang, Kaixin Zhang, Shuai Li, Zhongjun Chen & Lixin Li

    2. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China

      Xiaocheng Lu

    3. Department of Neurosurgery, Jiangxi Provincial People’s Hospital, 92 Aiguo Road, Nanchang, 330006, Jiangxi, China

      Ronglan Zhu

    4. Department of Neurosurgery, Huangshan City People’s Hospital, 4 Liyuan Road, Huangshan, 245000, Anhui, China

      Kaixin Zhang

    5. Department of Neurosurgery, The Second People’s Hospital of Huai’an, 62 Huaihainan Road, Huai’an, 223002, Jiangsu, China

      Zhongjun Chen

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    1. Xi Wang
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    Correspondence to Lixin Li.

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    Xi Wang and Xiaocheng Lu have contributed equally to this work.

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    Wang, X., Lu, X., Zhu, R. et al. Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway. Neurochem Res 42, 1130–1140 (2017). https://doi.org/10.1007/s11064-016-2147-y

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