Gambogic acid inhibits proliferation and induces apoptosis of human acute T-cell leukemia cells by inducing autophagy and downregulating -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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