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 µM 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 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.
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http://dx.doi.org/10.18632/oncotarget.3444 | DOI Listing |
Virus Res
January 2025
Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China; Shenzhen Immuthy Biotech Co., Ltd, 518107, Shenzhen, Guangdong, China. Electronic address:
Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatitis B core antigen (HBcAg) and the HBV relaxed-circular partially double-stranded DNA (rcDNA), indispensable in virus replication.
View Article and Find Full Text PDFJ Control Release
January 2025
Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address:
Hepatocellular carcinoma (HCC) is a leading cause of cancer death that has limited treatment options for advanced stages. Although PD-1 inhibitors such as nivolumab and pembrolizumab have been approved for advanced HCC treatment, their effectiveness is often hampered by the immunosuppressive tumor microenvironment (TME), which is due to hypoxia-driven CXCL12/CXCR4 axis activation. In this study, we developed 807-NPs, lipid-coated tannic acid (TA) nanoparticles that encapsulate BPRCX807, a potent CXCR4 antagonist to target HCC.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, China. Electronic address:
Pyroptosis and macrophage pro-inflammatory activation play an important role in hepatocellular carcinoma (HCC) progression. However, the specific regulatory mechanisms remain unclear. We identified pyroptosis-related differentially expressed genes (DEGs) based on the GSE4183 and GSE44861 datasets as well as EVenn database.
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January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China; Institute of Fundamental and Transdisciplinary Research, Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310029, China. Electronic address:
Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells.
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January 2025
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China. Electronic address:
Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is associated with poor survival. Formosanin C (FC) is a diosgenin glycoside extracted from Paris polyphylla. Therapeutic effects of FC against HCC malignancies remain unclear.
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