(Z)3,4,5,4 '-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level

doi:10.1038/srep16348

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

	(Z)3,4,5,4 '-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level
	Fan, Xing-Xing 6; Yao, Xiao-Jun 6; Xu, Su Wei 6; Wong, Vincent Kam-Wai 6; He, Jian-Xing 1; Ding, Jian2 ; Xue, Wei-Wei 4; Mujtaba, Tahira 5; Michelangeli, Francesco 5; Huang, Min2
刊名	SCIENTIFIC REPORTS
	2015-11-06
卷号	5
ISSN号	2045-2322
DOI	10.1038/srep16348
文献子类	Article
英文摘要	Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4'-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.
资助项目	FDCT grants from the Science and Technology Development Fund of Macao[021/2013/A1] ; Ministry of Science and Technology of the People's Republic of China[005/2014/AMJ] ; Ministry of Science and Technology of the People's Republic of China[L2015TGA9005] ; Macao Science and Technology Development Fund[005/2014/AMJ] ; Macao Science and Technology Development Fund[L2015TGA9005]
WOS关键词	SARCOPLASMIC-RETICULUM ; ANTICANCER AGENTS ; MTOR INHIBITORS ; APOPTOSIS ; GROWTH ; PATHWAYS ; PROTEIN ; MUTATIONS ; AUTOPHAGY ; UPSTREAM
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000364211800001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276330]
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	Liu, Liang
作者单位	1.Guangzhou Med Univ, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China; 3.Chinese Univ Hong Kong, Dept Chem Pathol, Fac Med, Hong Kong, Hong Kong, Peoples R China; 4.Chongqing Univ, Innovat Drug Res Ctr, Chongqing 630044, Peoples R China; 5.Univ Chester, Dept Biol Sci, Chester, Cheshire, England 6.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau Inst Appl Res Med & Hlth, Macau, Peoples R China;
推荐引用方式 GB/T 7714	Fan, Xing-Xing,Yao, Xiao-Jun,Xu, Su Wei,et al. (Z)3,4,5,4 '-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level[J]. SCIENTIFIC REPORTS,2015,5.
APA	Fan, Xing-Xing.,Yao, Xiao-Jun.,Xu, Su Wei.,Wong, Vincent Kam-Wai.,He, Jian-Xing.,...&Leung, Elaine Lai-Han.(2015).(Z)3,4,5,4 '-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level.SCIENTIFIC REPORTS,5.
MLA	Fan, Xing-Xing,et al."(Z)3,4,5,4 '-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level".SCIENTIFIC REPORTS 5(2015).