ArticleOncotarget2015
Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
- Oxidative Stress and Diminished Mitochondrial Proteostatic Reserve Are Linked to Enhanced mtUPR Initiation in Aged Mouse Muscle.Aging cell · 2026Article
- Exposure of piperlongumine attenuates stemness and epithelial to mesenchymal transition phenotype with more potent anti-metastatic activity in SOX9 deficient human lung cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.International journal of molecular sciences · 2024Article
- Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.Heliyon · 2024Review
- Piperlongumine regulates genes involved in the skin barrier in epidermal keratinocyte HaCaT cells.Animal cells and systems · 2024Article
- The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.Frontiers in pharmacology · 2024Review
- The Antitumor Activity of Piplartine: A Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Ferroptosis-modulating small molecules for targeting drug-resistant cancer: Challenges and opportunities in manipulating redox signaling.Medicinal research reviews · 2023Review
- Piperlongumine Induces Cellular Apoptosis and Autophagy via the ROS/Akt Signaling Pathway in Human Follicular Thyroid Cancer Cells.International journal of molecular sciences · 2023Article
- Alcohol extracts of Chinese bayberry branch induce S-phase arrest and apoptosis in HepG2 cells.Food science & nutrition · 2023Article
- Suppressive Effects ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Piperlongumine increases the sensitivity of bladder cancer to cisplatin by mitochondrial ROS.Journal of clinical laboratory analysis · 2022Article
- Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: involvement of glucose import, ROS, NF-κB and lncRNAs.Apoptosis : an international journal on programmed cell death · 2022Article
- Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS-STAT3 pathway.The Journal of international medical research · 2022Article
- Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway.Frontiers in cell and developmental biology · 2022Article
- Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux.Biological research · 2021Article
- Article
- Piperlongumine Inhibits Zika Virus Replication In vitro and Promotes Up-Regulation of HO-1 Expression, Suggesting An Implication of Oxidative Stress.Virologica Sinica · 2021Article
- Antileishmanial activity evaluation of a natural amide and its synthetic analogs against Leishmania (V.) braziliensis: an integrated approach in vitro and in silico.Parasitology research · 2021Article
- Piperlongumine promotes death of retinoblastoma cancer cells.Oncotarget · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 10-20 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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