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Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stress-induced cell death 期刊论文

编号：

7f2f771d-2e3e-4f8d-8800-576578105cb4
作者：

Wu, Man(吴曼)#^[1,2]Lao, Yuanzhi(劳远至)^[1,2]Xu, Naihan^[3];Wang, Xiaoyu^[1,2];Tan, Hongsheng(谭红胜)^[1,2]Fu, Wenwei(付文卫)^[1,2]Lin, Zhixiu^[4];Xu, Hongxi(徐宏喜)*^[1,2]
语种：

英文
期刊：

PHYTOMEDICINE ISSN：0944-7113 2015 年 22 卷 10 期 (902 - 910) ; SEP 15
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关键词：

Apoptosis Autophagy Guttiferone K Natural compound Starvation
摘要：

Background: Medicinal plants have long been an excellent source of pharmaceutical agents. Autophagy, a catabolic degradation process through lysosomes, plays an important role in tumorigenesis and cancer therapy.
Purpose: Through a screen designed to identify autophagic regulators from a library of natural compounds, we found that Guttiferone K (GUTK) can activate autophagy in several cancer cell lines. The objective of this study is to investigate the mechanism by which GUTK sensitizes cancer cells to cell death in nutrient starvation condition.
Methods: Cell death analysis was performed by propidium iodide staining with flow cytometry or Annexin V-FITC/PI staining assay. DCFH-DA staining was used for intracellular ROS measurement. Protein levels were analyzed by western blot analysis. Cell viability was measured by MTT assay.
Results: Exposure to GUTK was observed to markedly induce GFP-LC3 puncta formation and activate the accumulation of LC3-II and the degradation of p62 in HeLa cells, suggesting that GUTK is an autophagy inducer. Importantly, hydroxychloroquine, an autophagy inhibitor, was found to significantly prevent GUTK-induced cell death in nutrient starvation conditions, suggesting that the cell death observed is largely dependent on autophagy. We further provide evidence that GUTK inhibits Akt phosphorylation, thereby inhibiting the mTOR pathway in cancer cells during nutrient starvation. In addition, GUTK causes the accumulation of reactive oxygen species (ROS) and the phosphorylation of JNK in EBSS, which may mediate both autophagy and apoptosis.
Conclusion: These data indicate that GUTK sensitizes cancer cells to nutrient stress-induced cell death though Akt/mTOR dependent autophagy pathway. (C) 2015 The Authors. Published by Elsevier GmbH.
推荐引用方式
GB/T 7714：

Wu Man,Lao Yuanzhi,Xu Naihan, et al. Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stress-induced cell death [J].PHYTOMEDICINE,2015,22(10):902-910.
APA：

Wu Man,Lao Yuanzhi,Xu Naihan,Wang Xiaoyu,&Xu Hongxi.(2015).Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stress-induced cell death .PHYTOMEDICINE,22(10):902-910.
MLA：

Wu Man, et al. "Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stress-induced cell death" .PHYTOMEDICINE 22,10(2015):902-910.
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