ArticlePloS one2012
Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Heme oxygenase-1 leads to cisplatin resistance in nasopharyngeal carcinoma by reducing oxidative stress and ferroptosis.Cancer cell international · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- A double layer oral film loaded with doxepin hydrochloride for the treatment of chemotherapy-induced oral mucositis.Frontiers in pharmacology · 2025Article
- Dual blockage of PI3K-mTOR and FGFR induced autophagic cell death in cholangiocarcinoma cells.Heliyon · 2024Article
- Corosolic Acid Induced Apoptosis via Upregulation of Bax/Bcl-2 Ratio and Caspase-3 Activation in Cholangiocarcinoma Cells.ACS omega · 2024Article
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Protective effect of andrographolide against ulcerative colitis by activating Nrf2/HO-1 mediated antioxidant response.Frontiers in pharmacology · 2024Article
- Free heme exacerbates colonic injury induced by anti-cancer therapy.Frontiers in immunology · 2023Article
- Role of Keap1-Nrf2/ARE signal transduction pathway in protection of dexmedetomidine preconditioning against myocardial ischemia/reperfusion injury.Bioscience reports · 2022Article
- Enhancing Bioactive Components ofAntioxidants (Basel, Switzerland) · 2022Article
- PrPMolecular neurobiology · 2022Article
- Ellagic Acid Alleviates Diquat-Induced Jejunum Oxidative Stress in C57BL/6 Mice through Activating Nrf2 Mediated Signaling Pathway.Nutrients · 2022Article
- Immune Modulation by Inhibitors of the HO System.International journal of molecular sciences · 2020Review
- Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase-1 expression in cholangiocarcinoma cell lines.Oncology letters · 2020Article
- Effects of curcumin complexes on MDA‑MB‑231 breast cancer cell proliferation.International journal of oncology · 2020Article
- Non-competitive heme oxygenase-1 activity inhibitor reduces non-small cell lung cancer glutathione content and regulates cell proliferation.Molecular biology reports · 2020Article
- Stimulated upregulation ofOncology letters · 2019Article
- Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect.International journal of biological sciences · 2019Article
- Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells acquire drug resistance via various mechanisms including enhanced cellular cytoprotective and antioxidant activities. Heme oxygenase-1 (HO-1) is a key enzyme exerting potent cytoprotection, cell proliferation and drug resistance. We aimed to investigate roles of HO-1 in human cholangiocarcinoma (CCA) cells for cytoprotection against chemotherapeutic agents. KKU-100 and KKU-M214 CCA cell lines with high and low HO-1 expression levels, respectively, were used to evaluate the sensitivity to chemotherapeutic agents, gemcitabine (Gem) and doxorubicin. Inhibition of HO-1 by zinc protoporphyrin IX (ZnPP) sensitized both cell types to the cytotoxicity of chemotherapeutic agents. HO-1 gene silencing by siRNA validated the cytoprotective effect of HO-1 on CCA cells against Gem. Induction of HO-1 protein expression by stannous chloride enhanced the cytoprotection and suppression of apoptosis caused by anticancer agents. The sensitizing effect of ZnPP was associated with increased ROS formation and loss of mitochondrial transmembrane potential, while Gem alone did not show any effects. A ROS scavenger, Tempol, abolished the sensitizing effect of ZnPP on Gem. Combination of ZnPP and Gem enhanced the release of cytochrome c and increased p21 levels. The results show that HO-1 played a critical role in cytoprotection in CCA cells against chemotherapeutic agents. Targeted inhibition of HO-1 may be a strategy to overcome drug resistance in chemotherapy of bile duct cancer.
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