ArticleMolecular cancer2009
Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo.
Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 103 citations in OpenAlex.
- Heme oxygenase-1 leads to cisplatin resistance in nasopharyngeal carcinoma by reducing oxidative stress and ferroptosis.Cancer cell international · 2025Article
- Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.Annals of medicine and surgery (2012) · 2024Article
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Heme Oxygenase-1 Inhibition Modulates Autophagy and Augments Arsenic Trioxide Cytotoxicity in Pancreatic Cancer Cells.Biomedicines · 2023Article
- Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.Journal of experimental & clinical cancer research : CR · 2023Article
- HMOX1 pathway signature predicts clinical benefit from immunotherapy plus tyrosine kinase inhibitor therapy in advanced renal cell carcinoma.Cancer medicine · 2023Article
- Differentiation of Hodgkin lymphoma cells by reactive oxygen species and regulation by heme oxygenase-1 through HIF-1α.Cancer science · 2021Article
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- Novel therapies targeting hypoxia mechanism to treat pancreatic cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2021Article
- Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?Antioxidants (Basel, Switzerland) · 2021Review
- Loss of SWI/SNF Chromatin Remodeling Alters NRF2 Signaling in Non-Small Cell Lung Carcinoma.Molecular cancer research : MCR · 2020Article
- Heme oxygenase promotes B-Raf-dependent melanosphere formation.Pigment cell & melanoma research · 2020Article
- A preclinical evaluation of thiostrepton, a natural antibiotic, in nasopharyngeal carcinoma.Investigational new drugs · 2020Article
- p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells.Journal of Cancer · 2020Article
- Stimulated upregulation ofOncology letters · 2019Article
- 14-3-3ζ inhibits heme oxygenase-1 (HO-1) degradation and promotes hepatocellular carcinoma proliferation: involvement of STAT3 signaling.Journal of experimental & clinical cancer research : CR · 2019Article
- A Dual Role of Heme Oxygenase-1 in Cancer Cells.International journal of molecular sciences · 2018Review
- A review on heme oxygenase-1 induction: is it a necessary evil.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy in vitro. Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells. PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested in vivo and in vitro.
resultsHigh HO-1 expression in PaCa cell lines was associated with increased chemoresistance in vitro. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects in vivo significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.
conclusionIn summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy in vivo. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.
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