Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP

	Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP
	Chen, Y; Liu, JM; Xiong, XX; Qiu, XY; Pan, F; Liu, D; Lan, SJ; Jin, S; Yu, SB; Chen, XQ
刊名	ONCOTARGET
	2015
卷号	6 期号:8 页码:6406-6421
关键词	piperlongumine hepatocellular carcinoma oxidative stress signaling pathway chemotherapy
通讯作者	Chen, XQ (reprint author), Huazhong Univ Sci & Technol, Hubei Prov Key Lab Neurol Dis, Inst Brain Res,Key Lab Neurol Dis,Minist Educ, Dept Pathophysiol,Sch Basic Med,Tongji Med Coll, Wuhan 430074, Peoples R China.,chenxq@mails.tjmu.edu.cn
英文摘要	Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 mu M while PL at much lower concentrations only suppressed HCC cell migration/invasion. PL selectively elevated reactive oxygen species (ROS) in HCC cells, which activated or up-regulated downstream PERK/Ire 1a/Grp78, p38/JNK/Erk and CHOP subsequently. Administration of antioxidants completely abolished PL's effects on cell death and migration/invasion. However, pharmacological inhibition of ER stressresponses or MAPKs signaling pathways with corresponding specific inhibitors only reversed PL's effect on cell migration/invasion but not on cell death. Consistently, knocking-down of CHOP by RNA interference only reversed PL-suppressed HCC cell migration. Finally, PL significantly suppressed HCC development and activated the ER-MAPKs-CHOP signaling pathway in HCC xenografts in vivo. Taken together, PL selectively killed HCC cells and preferentially inhibited HCC cell migration/invasion via ROS-ER-MAPKs-CHOP axis, suggesting a novel therapeutic strategy for the highly malignant and aggressive HCC clinically.
学科主题	Oncology ; Cell Biology
类目[WOS]	Oncology ; Cell Biology
关键词[WOS]	ENDOPLASMIC-RETICULUM STRESS ; BREAST-CANCER CELLS ; DOWN-REGULATION ; APOPTOSIS ; DEATH ; ACTIVATION ; INDUCTION ; PATHWAY ; GROWTH ; HEPATOCARCINOGENESIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000352793000066
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/87]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chen, Y,Liu, JM,Xiong, XX,et al. Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP[J]. ONCOTARGET,2015,6(8):6406-6421.
APA	Chen, Y.,Liu, JM.,Xiong, XX.,Qiu, XY.,Pan, F.,...&Chen, XQ.(2015).Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.ONCOTARGET,6(8),6406-6421.
MLA	Chen, Y,et al."Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP".ONCOTARGET 6.8(2015):6406-6421.