Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP
文献类型：期刊论文
| 作者 | Chen, Y; Liu, JM; Xiong, XX; Qiu, XY; Pan, F; Liu, D; Lan, SJ; Jin, S; Yu, SB; Chen, XQ |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 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 |
| 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. |
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