Cyclovirobuxine D inhibits the growth of osteosarcoma cells through the induction of autophagy flux arrest by promoting lysosomal acidification

作者全名：Liang, Shiqiong; Xie, Liping; Li, Ziyun; Lu, Qiuping; Zhang, Lulu; Wang, Jiayu; Xia, Haichao; Luo, Lijuan; Wang, Xiaoxuan; Luo, Jinyong

作者地址：[Liang, Shiqiong; Xie, Liping; Li, Ziyun; Lu, Qiuping; Zhang, Lulu; Wang, Jiayu; Xia, Haichao; Luo, Lijuan; Wang, Xiaoxuan; Luo, Jinyong] Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, 1 Yixueyuan Rd, Chongqing 40016, Peoples R China; [Luo, Jinyong] Chongqing Med Univ, Coll Lab Med, Key Lab Diagnost Med Designated, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing 40016, Peoples R China

通信作者：Luo, JY (通讯作者)，Chongqing Med Univ, Coll Lab Med, Key Lab Diagnost Med Designated, Chinese Minist Educ, 1 Yixueyuan Rd, Chongqing 40016, Peoples R China.

来源：JOURNAL OF FUNCTIONAL FOODS

ESI学科分类：AGRICULTURAL SCIENCES

WOS号：WOS:001236163000001

JCR分区：Q2

影响因子：3.8

年份：2024

卷号：116

期号：　

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结束页：　

文献类型：Article

关键词：Cyclovirobuxine D; Osteosarcoma; Autophagy; Lysosome; Acidification; V-ATPase

摘要：Osteosarcoma (OS) is an aggressive primary tumor with the highest incidence in children and adolescents. Natural plant compounds (NPCs) have long been promising resources in the field of antitumor drug discovery because of their high efficacy and low toxicity. Here, the aim of this study is to investigate the potential inhibitory effects of Cyclovirobuxine D (CVB-D), a natural bioactive isolated from the traditional Chinese medicinal herb Huangyang, on OS cells. We showed that CVB-D reduced OS cell growth in vitro and in vivo. Mechanistically, CVB-D inhibited PI3K-AKT-mTOR pathway and initiated autophagy. On the other hand, CVB-D induced lysosomal over-acidification by interacting with the V-type proton ATPase 116 kDa subunit a1 (ATP6V0A1), ultimately leading to autophagy flux arrest which might be related to the inhibitory effect of CVB-D on OS cells. Conclusively, our results propose a potential foundation for CVB-D to be developed into an anti-OS drug and an autophagy inhibitor.

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