Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells

doi:10.1016/j.jep.2020.113213

	Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells
	Shao, Chang-Sheng 2,3; Zhou, Xiu-Hong 1; Zheng, Xin-Xin 2,3; Huang, Qing 2,3
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	2020-11-15
卷号	262
关键词	Ganoderic acid D (GAD) Triterpenoid Esophageal squamous cell carcinoma (ESCC) Apoptosis Autophagy Autophagic flux
ISSN号	0378-8741
DOI	10.1016/j.jep.2020.113213
通讯作者	Huang, Qing(huangq@ipp.ac.cn)
英文摘要	Ethnophamacological relevance: Ganoderma lucidum has been used as a medicinal mushroom for more than 2000 years in China. Ganoderic acid D (GAD) as a representative active triterpenoid from Ganoderma lucidum is known to possess anticancer activity. However, the mechanism involved in its anticancer cell process is still largely elusive. Aim of the study: Our study aimed to investigate the anticancer effects of GAD on the esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanisms at the cell level. Materials and methods: EC9706 and Eca109 cells were treated with GAD (0, 10, 20, 40 mu M) for 24 h. The cell viability, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis rate, caspase-3 activity, autophagic flux, lysosomal function were examined. Cell cycle, apoptotic, autophagy and mTOR signal pathway related proteins such as P53, Cyclin B1, CytoC, PARP, Beclin-1, P62, LC3, PI3K, AKT and mTOR were analyzed by Western blot approach. Results: GAD inhibited cell proliferation and induced both apoptosis and autophagic cell death. In particular, we found that in the early stage of the autophagic process, GAD could initiate and enhance the autophagy signal while in the late stage it on the contrary could block the autophagic flux by impairing the autophagosome-lysosome fusion and inhibited the lysosomal degradation. Besides the autophagic cell death, GAD also induced the apoptosis mediated by caspase-related process in parallel. The mechanism involved for the synergistic apoptotic and autophagic cell death was also explored. We found that GAD down-regulated the expression of PI3K, AKT and mTOR phosphorylated proteins in the mTOR signaling pathway which thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells. Conclusions: In summary, this study has documented that GAD may inhibit cell proliferation through the mTOR pathway in ESCC cells, and induce synergistic apoptosis and autophagic cell death by disrupting the autophagic flux. This work therefore also suggests that GAD may be used as an efficient anticancer adjuvant for ESCC cancer therapy.
资助项目	National Natural Science Foundation of China[11635013] ; National Natural Science Foundation of China[11775272] ; Special Fund of Innovation and Purchase in Central-level Scientific Institutions[Y79XG13361]
WOS关键词	INHIBITION ; DRUG
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000569292700002
资助机构	National Natural Science Foundation of China ; Special Fund of Innovation and Purchase in Central-level Scientific Institutions
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/104136]
专题	中国科学院合肥物质科学研究院
通讯作者	Huang, Qing
作者单位	1.Anhui Agr Univ, Ctr Biol, Hefei, Peoples R China 2.Chinese Acad Sci, Inst Intelligent Machines, Hefei Inst Phys Sci, CAS Key Lab High Magnet Field & Ion Beam Phys Bio, Hefei 230031, Peoples R China 3.Univ Sci & Technol China, Hefei 230026, Peoples R China
推荐引用方式 GB/T 7714	Shao, Chang-Sheng,Zhou, Xiu-Hong,Zheng, Xin-Xin,et al. Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells[J]. JOURNAL OF ETHNOPHARMACOLOGY,2020,262.
APA	Shao, Chang-Sheng,Zhou, Xiu-Hong,Zheng, Xin-Xin,&Huang, Qing.(2020).Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells.JOURNAL OF ETHNOPHARMACOLOGY,262.
MLA	Shao, Chang-Sheng,et al."Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells".JOURNAL OF ETHNOPHARMACOLOGY 262(2020).