Fraxinellone Has Anticancer Activity by Inducing Osteosarcoma Cell Apoptosis via Promoting Excessive Autophagy Flux

Frontiers in Pharmacology

Wenkan Zhang²  Jiaming He²  Bin He³ 

[1] Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China;The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;The Second Affiliated Hospital, Zhejiang University School of medcine, Hangzhou, China;

关键词: fraxinellone;    proliferation;    cancer therapy;    autophagy;    apoptosis;   

DOI  :  10.3389/fphar.2021.653212

来源: DOAJ

【 摘 要 】

Osteosarcoma is a malignant bone tumor that is easy to metastasize in the early stage and has a very poor prognosis. Fraxinellone (FRA) is one of the main components isolated from the D. dasycarpus plant. Its anti-inflammatory and neuroprotective effects have been confirmed, but the research on the anti-cancer effect of FRA and its potential mechanism is relatively scarce. In this study, we found that FRA inhibited the proliferation and migration of osteosarcoma cells HOS and MG63 in a dose-dependent manner. Immunofluorescence, fluorescence staining and western blotting analysis showed that FRA could simultaneously induce osteosarcoma cell apoptosis and increase autophagy flux. Subsequent turnaround experiments suggested that the pro-apoptotic effect of FRA was achieved through excessive autophagy flux. The results of the xenograft orthotopic model further supported the anti-cancer effects of FRA, indicating that FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved in vivo. These studies provide new ideas for the future treatment of osteosarcoma and offer theoretical support for the anti-cancer mechanism of FRA.

【 授权许可】

Unknown