The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells

doi:10.1007/s10637-010-9481-8

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells
	Lu, Jin-Jian; Chen, Si-Meng; Zhang, Xiao-Wei; Ding, Jian; Meng, Ling-Hua
刊名	INVESTIGATIONAL NEW DRUGS
	2011-12
卷号	29 期号:6 页码:1276-1283
关键词	Dihydroartemisinin 2-DE ER stress GRP78 GADD153
ISSN号	0167-6997
DOI	10.1007/s10637-010-9481-8
文献子类	Article
英文摘要	Dihydroartemisinin (DHA), the main active metabolite of artemisinin derivatives, is among the artemisinin derivatives possessing potent anti-malarial and anti-cancer activities. In the present study, we found that DHA displayed significant anti-proliferative activity in human colorectal carcinoma HCT116 cells, which may be attributed to its induction of G1 phase arrest and apoptosis. To further elucidate the mechanism of action of DHA, a proteomic study employed two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed. Glucose-regulated protein 78 (GRP78), which is related with endoplasmic reticulum stress (ER stress), was identified to be significantly up-regulated after DHA treatment. Further study demonstrated that DHA enhanced expression of GRP78 as well as growth arrest and DNA-damage-inducible gene 153 (GADD153, another ER stress-associated molecule) at both mRNA and protein levels. DHA treatment also led to accumulation of GADD153 in cell nucleus. Moreover, pretreatment of HCT116 cells with the iron chelator deferoxamine mesylate salt (DFO) abrogated induction of GRP78 and GADD153 upon DHA treatment, indicating iron is required for DHA-induced ER stress. This result is consistent with the fact that the anti-proliferative activity of DHA is also mediated by iron. We thus suggest the unbalance of redox may result in DHA-induced ER stress, which may contribute, at least in part, to its anti-cancer activity.
资助项目	National Natural Science of China[30701026] ; National Natural Science of China[30721005] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001]
WOS关键词	CANCER-CELLS ; IN-VIVO ; TUMOR-CELLS ; ARTEMISININ ; APOPTOSIS ; ARTESUNATE ; GROWTH ; VITRO ; CYTOTOXICITY ; ANGIOGENESIS
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000294824200016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278328]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Lu, Jin-Jian,Chen, Si-Meng,Zhang, Xiao-Wei,et al. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells[J]. INVESTIGATIONAL NEW DRUGS,2011,29(6):1276-1283.
APA	Lu, Jin-Jian,Chen, Si-Meng,Zhang, Xiao-Wei,Ding, Jian,&Meng, Ling-Hua.(2011).The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells.INVESTIGATIONAL NEW DRUGS,29(6),1276-1283.
MLA	Lu, Jin-Jian,et al."The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells".INVESTIGATIONAL NEW DRUGS 29.6(2011):1276-1283.