The Role of HO-1 and Its Crosstalk with Oxidative Stress in Cancer Cell Survival

Abstract

Heme oxygenases (HOs) act on heme degradation to produce carbon monoxide (CO), free iron, ferritin, and biliverdin. Upregulation of cellular HO-1 levels is signature of oxidative stress for its downstream effects particularly under pro-oxidative status. Subcellular traffics of HO-1 to different organelles constitute a network of interactions compromising a variety of effectors such as pro-oxidants, ROS, mitochondrial enzymes, and nucleic transcription factors. Some of the compartmentalized HO-1 have been demonstrated as functioning in the progression of cancer. Emerging data show the multiple roles of HO-1 in tumorigenesis from pathogenesis to the progression to malignancy, metastasis, and even resistance to therapy. However, the role of HO-1 in tumorigenesis has not been systematically addressed. This review describes the crosstalk between HO-1 and oxidative stress, and following redox regulation in the tumorigenesis. HO-1-regulated signaling pathways are also summarized. This review aims to integrate basic information and current progress of HO-1 in cancer research in order to enhance the understandings and facilitate following studies.

Cold Plasma Irradiation Attenuates Atopic Dermatitis via Enhancing HIF-1α-Induced MANF Transcription Expression

“…The inflammatory response is often accompanied by ER stress and oxidative stress responses ( 26 ). Accordingly, we examined the commonly-used indicators of inflammation, ER stress and oxidative stress, including Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β) ( 27 ), High Mobility Group Box 1 (HMGB1) ( 28 ), Chemokine CCL2 ( 29 ), Glucose Regulated Protein 78 (GRP78, also known as Bip), CCAAT/enhancer binding protein homologous protein (CHOP) ( 30 ), Heme Oxygenase-1 (HO-1) ( 31 ) and MANF. IHC, WB and RT-qPCR results showed that DNFB stimulation could promote expressions of pro-inflammatory cytokines TNF-α and IL-1β, Chemokine CCL2, pro-inflammatory HMGB1, ER stress-related proteins Bip and CHOP, oxidative stress-related protein HO-1 in skin tissues of mice, indicating DNFB-induced AD mice had the greater inflammation, ER stress and oxidative stress responses compared with untreated mice; also, CAP treatment partly alleviated DNFB-induced skin inflammation, ER stress and oxidative stress ( Figures 2A–C and S2A, B ).…”

Cyclophosphamide Induces the Ferroptosis of Tumor Cells Through Heme Oxygenase-1

“…Chiang SK et al postulated that HMOX-1 is activated as a cytoprotective defense mechanism or governs ferroptotic progression that depends on the degree to which HMOX-1 expression is increased in response to stimulatory cues ( Chiang et al, 2018 ). When HMOX-1 expression is moderately activated, NRF2-derived HMOX-1 exerts a cytoprotective effect by neutralizing ROS; while a high degree of HMOX-1 activation increases LIP, leading to ROS overload and subsequent oxidative cell death ( Chiang et al, 2021 ). Our in vivo and in vitro experimental results using the HMOX-1 agonist Hemin support this hypothesis, and the application of HMOX-1 modulators to mediate ferroptosis might be a new strategy for cancer chemotherapy.…”

Gegen Qinlian Decoction Relieves Ulcerative Colitis via Adjusting Dysregulated Nrf2/ARE Signaling

“…NQO1 plays a vital role in antioxidant stress by maintaining the reduction state of coenzyme Q and vitamin E [ 26 ]. HO-1 has a protective effect on the body tissues and maintains the redox homeostasis [ 27 – 29 ] in the body. GCLC and GCLM formed glutamyl-L-cysteine ligase, which catalyzed the de novo synthesis of GSH [ 30 ].…”