Dihydroartemisinin Modulates Apoptosis and Autophagy in Multiple Myeloma through the P38/MAPK and Wnt/β-Catenin Signaling Pathways
Dihydroartemisinin Modulates Apoptosis and Autophagy in Multiple Myeloma through the P38/MAPK and Wnt/β-Catenin Signaling Pathways
复制标题
双氢青蒿素通过 P38/MAPK 和 Wnt/β-Catenin 信号通路调节多发性骨髓瘤中的细胞凋亡和自噬
DOI：
10.1155/2020/6096391
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发表时间：
2020-08-17
影响因子：
--
通讯作者：
Cai, Zhen
中科院分区：
文献类型：
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作者：
Wu, Xiuhua;Liu, Yang;Cai, Zhen
双氢青蒿素(DHA)是青蒿素的活性代谢物和衍生物，是目前最有效的抗疟疾药物，在多种肿瘤类型中具有很强的抗肿瘤活性。最近有报道称DHA可诱导自噬，对多发性骨髓瘤(MM)有显著作用，但其诱导自噬与细胞凋亡的机制及相互关系尚不清楚。在此，我们证明了DHA通过外在和内在的凋亡途径以剂量和时间依赖的方式显著地诱导细胞死亡。此外，DHA诱导的自噬在多发性骨髓瘤中起促死亡作用，可以调节典型的细胞凋亡，反之亦然。此外，P38/MAPK信号通路与自噬减少和细胞凋亡增加有关。DHA还通过抑制Wnt/β-Catenin信号通路诱导自噬和细胞凋亡。此外，DHA在异种移植小鼠模型中显示出很强的作用。总之，这些发现表明DHA作为一种以青蒿素为基础的药物，可能是一种有效和安全的MM治疗剂。
Dihydroartemisinin (DHA), an active metabolite and derivative of artemisinin, is the most effective antimalarial drug and has strong antitumor activity in various tumor types. It has recently been reported that DHA can induce autophagy and has significant effects on multiple myeloma (MM), but the mechanisms and the relationship between the autophagy and apoptosis induced by DHA remain to be elucidated. Herein, we demonstrated that DHA significantly induces cell death in a dose- and time-dependent manner via the extrinsic and intrinsic apoptosis pathways. Moreover, DHA-induced autophagy, which plays a prodeath role in MM, can regulate canonical apoptosis and vice versa. Furthermore, the P38/MAPK signaling pathway is responsible for decreased autophagy and increased apoptosis. DHA induces autophagy and apoptosis also through the inhibition of the Wnt/β-catenin signaling pathway. In addition, DHA shows a strong effect in a xenograft mouse model. Collectively, these findings reveal that DHA, as an artemisinin-based drug, could be an effective and safe therapeutic agent for MM.