Gambogic acid inhibits proliferation and induces apoptosis of human acute T‑cell leukemia cells by inducing autophagy and downregulating β‑catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T‑ALL cells.
ONCOLOGY REPORTS(2020)
摘要
The main active compound of Garcinia hanburyi (referred to as gamboge) is gambogic acid (GA), which has long been a Chinese herbal medicine for treating several types of cancer. However, the potential therapeutic role and mechanisms of GA in T-cell acute lymphoblastic leukemia (T-ALL) remain unclear. In the present study, the effects of GA on proliferation, cell cycle, apoptosis, and autophagy in T-ALL cell lines were investigated. The possible mechanisms underlying GA activity were also examined. The results showed that GA inhibited proliferation, induced apoptosis, and activated autophagy in T-ALL cell lines (Jurkat and Molt-4 cells). Findings confirmed that GA has an antileukemia effect against peripheral blood lymphocyte cells in patients with ALL. GA inhibited phospho-GSK3 beta S9 (p-GSK3 beta S9) protein levels to inactivate Wnt signaling and suppress beta-catenin protein levels. In addition, the inhibitory effect of GA on T-ALL was reversed by overexpression of beta-catenin. Thus, GA can inhibit the growth and survival of T-ALL cells. GA also had antileukemic activity, at least in part, through the downregulation of the Wnt/beta-catenin signaling pathway.
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关键词
T-cell acute lymphoblastic leukemia,gambogic acid,Wnt/beta-catenin,apoptosis,proliferation,autophagy
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