Importance of Heme Oxygenase-1 in Gastrointestinal Cancers: Functions, Inductions, Regulations, and Signaling

Abstract

Introduction 

Colorectal cancer (CRC) is one of the important gastrointestinal tract tumors. Heme is mainly absorbed in the colon and induces nitrosamine formation, genotoxicity,  and oxidative stress, and increases the risk of CRC.

Materials and Methods

Information was collected from articles on Scopus, Google Scholar, and PubMed.

Results

Heme can irritate intestinal epithelial cells and increases the proliferation of colonic mucosa. Heme can be considered as a carcinogenic agent for CRC induction. In typical situations, Heme Oxygenase-1 (HO-1) is expressed at low concentration in the gastrointestinal tract, but its expression is elevated during lesion and inflammation. Based on the multiple reports, the impact of HO-1 on tumor growth is related to the cancer cell type. Increased HO‐1 levels were also indicated in different human and animal malignancies, possibly through its contribution to tumor cell growth, metastasis, expression of angiogenic factors, and resistance to chemotherapy. Recent studies noted that HO-1 can act as an immunomodulator that suppresses immune cell maturation, activation, and infiltration. It also inhibits apoptosis through CO production that leads to p53 suppression. The upregulation of HO-1 significantly increases the endurance of colon cancer cell lines. Therefore, it is supposed that HO-1 inhibitors could become a novel antitumor agent. Lactobacillus rhamnosus and its metabolites can activate Nrf2 and improves anti-oxidant levels along with upregulation of its objective genes like HO-1, and downregulation of NF-κB which reduce phosphorylated TNF-α, IL-1β, and PAI-1.

Conclusion

The precise mechanism accountable for the anti-inflammatory features of HO-1 is not completely understood; nevertheless, the CO signaling function associated with the antioxidant property shown by bilirubin possibly will play an act in the improvement of inflammation.

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Acknowledgments

Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran, and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.

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Hemmati, M., Yousefi, B., Bahar, A. et al. Importance of Heme Oxygenase-1 in Gastrointestinal Cancers: Functions, Inductions, Regulations, and Signaling. J Gastrointest Canc (2021). https://doi.org/10.1007/s12029-021-00587-0

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Keywords

  • Colorectal cancer
  • Heme oxygenase-1
  • Microbiota
  • Inflammatory
  • Autophagy