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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Oncotarget. 2015 Mar 20 ;6(8):6406-21. PMID: 25788268

Abstract Author(s):

Yong Chen, Ju Mei Liu, Xin Xin Xiong, Xin Yao Qiu, Feng Pan, Di Liu, Shu Jue Lan, Si Jin, Shang Bin Yu, Xiao Qian Chen

Article Affiliation:

Yong Chen

Abstract:

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 10-20µM 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 1α/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 stress-responses 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 RNAinterference 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 viaROS-ER-MAPKs-CHOP axis, suggesting a novel therapeutic strategy for the highly malignant and aggressive HCC clinically.

Study Type : In Vitro Study

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Sayer Ji
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