ArticleMolecules and cells2015
Heme oxygenase-1 determines the differential response of breast cancer and normal cells to piperlongumine.
Article in Molecules and cells, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Piplartine as an Innovative Natural Product With Dual Antiparasitic and Immunomodulatory Actions.Journal of immunology research · 2026Review
- Cepharanthine Induces Oxidative Stress and Apoptosis in Cervical Cancer via the Nrf2/Keap1 Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- 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
- Prognostic value of Nrf2/HO-1 expression and its correlation with occurrence in esophageal squamous cell carcinoma.Genes & genomics · 2023Article
- 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
- Regulated cell death (RCD) in cancer: key pathways and targeted therapies.Signal transduction and targeted therapy · 2022Review
- Systems biology reveals anatabine to be an NRF2 activator.Frontiers in pharmacology · 2022Article
- Curcumin prevents AsChinese medicine · 2021Article
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- 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
- Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role.Antioxidants (Basel, Switzerland) · 2021Review
- Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway.BMC complementary medicine and therapies · 2021Article
- The promising potential of piperlongumine as an emerging therapeutics for cancer.Exploration of targeted anti-tumor therapy · 2021Review
- Review
- Natural Antioxidant and Anti-Inflammatory Compounds in Foodstuff or Medicinal Herbs Inducing Heme Oxygenase-1 Expression.Antioxidants (Basel, Switzerland) · 2020Review
- Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase-1 expression in cholangiocarcinoma cell lines.Oncology letters · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,β-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.