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  • Title: Gambogic acid-induced autophagy in nonsmall cell lung cancer NCI-H441 cells through a reactive oxygen species pathway.
    Author: Ye L, Zhou J, Zhao W, Jiao P, Ren G, Wang S.
    Journal: J Cancer Res Ther; 2018 Dec; 14(Supplement):S942-S947. PubMed ID: 30539827.
    Abstract:
    AIM OF THE STUDY: Garcinia hanburyi is a traditional herbal medicine with activities of anti-inflammation and hemostasis used by people in South Asia. Gambogic acid (GA) is the main active component extracted from it, which has anticancer and anti-inflammatory effects. The aim of the current study is to investigate the molecular mechanisms of GA's effective anticancer activity. MATERIALS AND METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to measure cell proliferation. Apoptosis induced by GA was analyzed by flow cytometry. In addition, monodansylcadaverine (MDC) and 2',7'-dichlorofluorescein diacetate were used to evaluate autophagy and reactive oxygen species (ROS) generation, respectively. RESULTS: GA could significantly inhibit nonsmall cell lung cancer (NSCLC) NCI-H441 cell growth. In addition, GA induced NCI-H441 cells autophagy, confirmed by MDC staining, upregulation of Beclin 1 (initiation factor for autophagosome formation), and conversion of LC3 I to LC3 II (autophagosome marker). Moreover, generated ROS was induced by GA in NCI-H441 cells and the ROS scavenger N-acetylcysteine reversed GA-induced autophagy and restored the cell survival, which indicated GA-induced autophagy in NCI-H441 cells through an ROS-dependent pathway. In addition, in vivo results further indicated that GA significantly inhibited the growth of NCI-H441 xenografts. CONCLUSIONS: The results shed new light on the interaction between ROS generation and autophagy in NSCLC cells and provide theoretical support for the usage of GA in clinical treatment.
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