Heme oxygenase-1 & 2 and their potential contribution in heme induced colorectal carcinogenesis

Sujani M K Gamage; Sachith Nanayakkara; Lilian Macfarlane; Dinu Hewage; Tracie Cheng; Sharmin Aktar; Cu Tai Lu; Lakal Dissabandara; Farhadul Islam; Alfred King-Yin Lam; Vinod Gopalan

doi:10.1016/j.prp.2022.153885

Heme oxygenase-1 & 2 and their potential contribution in heme induced colorectal carcinogenesis

Pathol Res Pract. 2022 May:233:153885. doi: 10.1016/j.prp.2022.153885. Epub 2022 Apr 7.

Affiliations

¹ Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia; Department of Anatomy, Faculty of Medicine, University of Peradeniya, Peradeniya 20404, Sri Lanka.
² Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia.
³ Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia; Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh.
⁴ Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, Bangladesh.
⁵ Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia. Electronic address: a.lam@griffith.edu.au.
⁶ Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia. Electronic address: v.gopalan@griffith.edu.au.

PMID: 35428017
DOI: 10.1016/j.prp.2022.153885

Abstract

Background: Literature suggests Heme oxygenase (HO) system to be a double-edged sword which can promote both cytoprotection as well as carcinogenicity. The aim of this study was to investigate the role of heme in HO-1 and HO-2 induced colorectal carcinogenesis and the clinicopathological significance of their expressions in patients with colorectal carcinoma (CRC).

Methods: HO-1 and HO-2 expression alterations in normal colonic epithelial (FHC) and colon cancer cells (SW480) were explored following treatment with 0 µM, 25 µM, 100 µM and 250 µM concentrations of hemin, using qPCR. Fifty paired CRC and adjacent non-neoplastic samples were subjected to qPCR to determine the HO-1 and HO-2 expression. Clinicopathological associations of HO-1 and HO-2 expression levels were determined.

Results: Low concentrations of hemin caused upregulation and high concentration caused downregulation of HO-1 expression, whereas HO-2 expression was significantly downregulated with all hemin concentrations in FHC. HO-1 expression in SW480 was increased with all hemin concentrations and HO-2 expression was downregulated at the highest hemin concentration. HO-1 and HO-2 expressions in adjacent non-neoplastic tissue was significantly higher than that of CRC. Expression of HO-1 was significantly higher than HO-2, in both CRC and adjacent non-neoplastic tissue. Sex, HFE expression and lymph-vascular invasion were significantly correlated with HO-1 expression. HO-2 expression showed significant associations with staging, local spread and recurrence of tumour.

Conclusion: HO-1 and HO-2 expression is respectively induced and repressed by exogenous hemin in normal colon and colon cancer cells. HO-1 and HO-2 expression profiles in CRC are correlated with the assessed clinicopathological features of CRC, suggesting the possible implications of HO expression status in CRC pathogenesis.

Keywords: Carcinogenesis; Colorectal cancer; Heme oxygenase; Hemin; Patient survival.

MeSH terms

Carcinogenesis
Colonic Neoplasms*
Colorectal Neoplasms*
Heme
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Hemin / pharmacology
Humans

Substances

Heme
Hemin
HMOX1 protein, human
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
heme oxygenase-2