DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer

doi:10.3389/fcell.2021.760022

	DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer
	Shu, Yuhan 2,4; Sun, Xin 4; Ye, Guiqin 1; Xu, Mengting 3; Wu, Zhipan 3; Wu, Caixia 4; Li, Shouxin 3; Tian, Jingkui 3; Han, Haote 3; Zhang, Jianbin 4
刊名	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
	2021-12-17
卷号	9
关键词	DHOK transcriptome sequencing autophagy colorectal cancer mTOR pathway
ISSN号	2296-634X
DOI	10.3389/fcell.2021.760022
通讯作者	Han, Haote(zhangjianbin@hmc.edu.cn) ; Zhang, Jianbin(hanhaote@163.com)
英文摘要	DHOK (14,15 beta-dihydroxyklaineanone) is a novel diterpene isolated from roots of Eurycoma longifolia Jack, a traditional herb widely applied in Southeast Asia. It is reported that DHOK has cytotoxic effect on cancer cells, but its anti-cancer mechanism has still been not clear. In our study, we first observed that DHOK inhibits cell proliferation of colorectal cancer cells in a time- and dose-dependent manner. Next, we performed transcriptome sequencing to identify the targets of DHOK and found that autophagy-related signaling pathways are involved under DHOK treatment. Indeed, in DHOK-treated cells, the level of autophagosome marker LC3 and the formation of GFP-LC3 puncta were decreased, indicating the reduction of autophagy. Moreover, confocal microscopy results revealed the lysosomal activity and the formation of autolysosomes are also inhibited. Our western blotting results demonstrated the activation of mammalian target of rapamycin (mTOR) signaling pathway by DHOK, which may be attributed to the enhancement of ERK and AKT activity. Functionally, activation of autophagy attenuated DHOK-caused cell death, indicating that autophagy serves as cell survival. In xenograft mouse model, our results also showed that DHOK activates the mTOR signaling pathway, decreases autophagy level and inhibits the tumorigenesis of colon cancer. Taken together, we revealed the molecular mechanism of DHOK against cancer and our results also demonstrate great potential of DHOK in the treatment of colorectal cancer.
资助项目	Zhejiang Provincial Natural Science Foundation[LR18H160002] ; Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program ; Zhejiang Provincial Qianjiang Talents Program ; National Natural Science Foundation of China[32070740] ; Jiangsu Provincial Natural Science Foundation of China[BK20201197]
WOS关键词	EURYCOMA-LONGIFOLIA JACK ; APOPTOSIS ; ACTIVATION ; PHOSPHORYLATION ; PATHWAYS ; SURVIVAL
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000738763300001
资助机构	Zhejiang Provincial Natural Science Foundation ; Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program ; Zhejiang Provincial Qianjiang Talents Program ; National Natural Science Foundation of China ; Jiangsu Provincial Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/127199]
专题	中国科学院合肥物质科学研究院
通讯作者	Han, Haote; Zhang, Jianbin
作者单位	1.Hangzhou Med Coll, Hangzhou, Peoples R China 2.Zhejiang Univ, Coll Biomed Engn & Instrument Sci, Hangzhou, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Inst Basic Med & Canc IBMC,Canc Hosp, Hangzhou, Peoples R China 4.Hangzhou Med Coll, Key Lab Tumor Mol Diag & Individualized Med Zheji, Hangzhou Med Coll,Canc Ctr, Zhejiang Prov Peoples Hosp,Peoples Hosp,Dept Onco, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Shu, Yuhan,Sun, Xin,Ye, Guiqin,et al. DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,9.
APA	Shu, Yuhan.,Sun, Xin.,Ye, Guiqin.,Xu, Mengting.,Wu, Zhipan.,...&Zhang, Jianbin.(2021).DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Shu, Yuhan,et al."DHOK Exerts Anti-Cancer Effect Through Autophagy Inhibition in Colorectal Cancer".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).