Abstract
Simple SummaryHeme is an iron-containing porphyrin that functions as a prosthetic group in hemoproteins and is involved in many biological processes. This review article summarizes (1) the varied effects of heme and heme oxygenase in tumorigenesis of different cancer types; (2) the molecular mechanisms of interaction of heme with regulatory and signaling proteins implicated in tumorigenesis, such as BACH1, PGRMC1, P53, CBS, sGC, and NOS; (3) the roles of altered heme levels and metabolism in the pathogenesis of diseases, including diabetes mellitus and Alzheimer’s dementia. Understanding the effects of heme in diverse cellular processes and disease progression identifies potential therapeutic targets and provides insights for developing novel treatment strategies.Heme is an essential prosthetic group in proteins and enzymes involved in oxygen utilization and metabolism. Heme also plays versatile and fascinating roles in regulating fundamental biological processes, ranging from aerobic respiration to drug metabolism. Increasing experimental and epidemiological data have shown that altered heme homeostasis accelerates the development and progression of common diseases, including various cancers, diabetes, vascular diseases, and Alzheimer’s disease. The effects of heme on the pathogenesis of these diseases may be mediated via its action on various cellular signaling and regulatory proteins, as well as its function in cellular bioenergetics, specifically, oxidative phosphorylation (OXPHOS). Elevated heme levels in cancer cells intensify OXPHOS, leading to higher ATP generation and fueling tumorigenic functions. In contrast, lowered heme levels in neurons may reduce OXPHOS, leading to defects in bioenergetics and causing neurological deficits. Further, heme has been shown to modulate the activities of diverse cellular proteins influencing disease pathogenesis. These include BTB and CNC homology 1 (BACH1), tumor suppressor P53 protein, progesterone receptor membrane component 1 protein (PGRMC1), cystathionine-β-synthase (CBS), soluble guanylate cyclase (sGC), and nitric oxide synthases (NOS). This review provides an in-depth analysis of heme function in influencing diverse molecular and cellular processes germane to disease pathogenesis and the modes by which heme modulates the activities of cellular proteins involved in the development of cancer and other common diseases.
Highlights
Heme is a tetrapyrrole containing a central iron ion essential for living organisms ranging from bacteria to humans [1,2]
These studies demonstrate that heme synthesis, export, and catabolism may be altered in pancreatic cancer and Colorectal cancer (CRC), affecting cellular metabolic pathways, and that dietary heme may play an additional role in colorectal carcinogenesis
This review summarizes recent literature on the association of heme and fundamental processes involved in the development of cancers and other related diseases (Figure 3)
Summary
Heme (iron–protoporphyrin IX) is a tetrapyrrole containing a central iron ion essential for living organisms ranging from bacteria to humans [1,2]. H1299, A549, H460, Calu-3, and H1395 NSCLC cell lines exhibit elevated heme synthesis and uptake as compared to two cell lines representing normal lung epithelial cells (HBEC30KT and NL20) These augmentations correlate with the increase of heme biosynthesis enzyme ALAS1, heme uptake protein HCP1/SLC46A1, and HO-1, respectively (Figure 1). Further studies are needed to fully explore the degree to which heme and other potential mechanisms contribute to the observed association between red meat and colorectal carcinogenesis, including the degree to which byproducts of lipid peroxidation such as 4-HNE may cause a selective effect that induces carcinogenesis Overall, these studies demonstrate that heme synthesis, export, and catabolism may be altered in pancreatic cancer and CRC, affecting cellular metabolic pathways, and that dietary heme may play an additional role in colorectal carcinogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
