Table 1.

Role of antioxidant genes Nrf2, Sestrin2 and HO-1 in metabolic disease and cancer

Gene	Involved Metabolic Diseases and Regulatory Mechanisms	Involved Cancer and Regulatory Mechanisms	Reference
Nrf2	Obesity: AMPK activation, reduction of lipogenesis, enhancement of β-oxidation, insulin sensitivity improvement Diabetes: Insulin sensitivity improvement, protection of pancreatic beta cells, reduction of oxidative stress, AMPK activation Non-alcoholic Steatohepatitis (NASH): Reduction of lipogenesis, enhancement of β-oxidation, AMPK activation	Colorectal Cancer: Chemoresistance through Nrf2 activation via KEAP1 and CUL3 mutations Breast Cancer: Chemoresistance via constitutive Nrf2 upregulation, leading to increased antioxidant gene expression Pancreatic Cancer: Chemoresistance enhancement, tumor progression through Nrf2 interaction with ATDC Gastric Cancer: Chemoresistance via Nrf2 activation and antioxidant gene upregulation Cervical Cancer: Increased chemosensitivity and suppression of tumor growth through Nrf2 inhibition or knockout Glioma: Tumor progression and poor prognosis through Nrf2 activation, suppression of tumorigenesis through Nrf2 knockout Non-Small Cell Lung Cancer (NSCLC): Tumor progression and treatment resistance through Nrf2 activation and interaction with PAQR4	26, 27, 70, 71, 78, 85, 89, 93, 95, 96, 97, 98
Sestrin2	Obesity: AMPK activation, inhibition of mTORC1 activity, enhancement of autophagy Diabetes: AMPK activation, improvement of insulin sensitivity, reduction of oxidative stress, inhibition of mTORC1 activity Insulin Resistance: AMPK activation, enhancement of autophagy, inhibition of mTORC1 activity Liver Fat Accumulation: Inhibition of Liver X receptor α, prevention of liver fat accumulation	Endometrial Cancer: mTORC1 inhibition, suppression of cancer cell proliferation, induction of autophagy Colorectal Cancer: mTORC1 inhibition, AMPK suppression, induction of apoptosis, reduction of cancer cell viability Lung Cancer: AKT/mTOR/P70S6K signaling suppression, inhibition of proliferation and migration of cancer cell Breast Cancer: mTORC1 inhibition, suppression of cancer progression, induction of apoptosis Hepatocellular Carcinoma: p53-dependent mechanisms, suppression of cancer progression, induction of autophagy Bone Cancer: mTORC1 inhibition, suppression of cancer cell proliferation, induction of autophagy Pancreatic Cancer: Inhibition of cancer cell migration, proliferation, and invasion through Nrf2/KEAP1/HO-1/NQO-1 signaling Bladder Cancer: Autophagy modulation, induction of apoptosis, suppression of cancer progression Cervical Cancer: Autophagy modulation, suppression of cancer progression, induction of apoptosis Osteosarcoma: mTOR inhibition through p-ERK-eIF2α-CHOP pathway, suppression of apoptosis, induction of chemoresistance Melanoma: Enhancement of cancer cell survival, promotion of chemoresistance, activation of AKT pathway	28, 29, 80, 131, 132, 133, 134, 137, 138, 139, 140, 141, 143, 144, 149, 150, 157
HO-1	Obesity: Maintenance of redox homeostasis, inhibition of adipogenesis, regulation of Peg1/Mest and Wnt10b/β-catenin/Sonic hedgehog signaling pathways Diabetes: Protection of pancreatic beta cells, reduction of oxidative stress, induction of glucose metabolism-related genes (e.g., GLUT4, adiponectin), activation of AMPK signaling Insulin Resistance: Improvement of insulin sensitivity, reduction of pro-inflammatory cytokines, activation of the HO-1-adiponectin axis, and AMPK signaling	Melanoma: Promotion of tumor aggressiveness, increased viability, proliferation, and metastasis Acute Myeloid Leukemia: Chemoresistance through HO-1 overexpression, reduced sensitivity to cytarabine and daunorubicin Multiple Myeloma: Induction of IL-6, increased resistance to lenalidomide treatment, survival factor promotion Lung Cancer: Promotion of lung metastasis, activation of VEGF and IL-10 Colon Cancer: Modulation of Nrf2/HO-1 signaling, upregulation of vimentin, downregulation of E-cadherin, suppression of immune responses Pancreatic Cancer: Activation of the Sonic Hedgehog (SHH) signaling pathway, promotion of cell proliferation Prostate Cancer: Controversial role; prevention of angiogenesis, progression of the tumor Breast Cancer: Dual role; promotion or suppression of tumor proliferation depending on angiogenesis and subcellular localization Head and Neck Cancer: Enhancement of cancer cell growth, pro-tumor activity enhancement	161, 164, 165, 166, 167, 168, 170, 179, 181, 182, 183, 184, 185, 186, 187, 188, 190, 199