Nrf2 signaling pathway in trace metal carcinogenesis: A cross-talk between oxidative stress and angiogenesis

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 254; p. 109266
• Main Authors: Emami, Mohammad Hassan, Sereshki, Nasrin, Malakoutikhah, Zahra, Dehkordi, Sayed Ali Ehsan, Fahim, Alireza, Mohammadzadeh, Samane, Maghool, Fatemeh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: Angiogenesis; Carcinogenesis; Carcinogenesis - chemically induced; Carcinogenesis - metabolism; Heavy metal; Humans; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress; Reactive Oxygen Species - metabolism; Signal Transduction; Oxidative stress; Angiogenesis; Nrf2; Carcinogenesis; Heavy metal
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2022.109266

A large number of people worldwide are affected by chronic metal exposure, which is known to be associated with different type of malignancies. The mechanisms of metal carcinogenicity are complex in nature, and excessive reactive oxygen species (ROS) generation induced by chronic metal exposure, among the other factors, has been proposed as one of the major mechanisms involved in that process. In tumor cells, ROS buildup may lead to cell death through intrinsic and extrinsic signaling pathways. Furthermore, ROS-mediated redox signaling has a crucial role in angiogenesis, which is recognized as an essential step in tumor progression. There are several redox-modulating pathways and among them, the nuclear factor erythroid2-related factor2 (Nrf2), as a sensor of oxidative or electrophilic stress, has introduced as a master regulator of cellular response against environmental stresses. Activation of Nrf2 signaling induces expression of wide variety of antioxidant and detoxification enzymes genes. Thus, this transcription factor has recently received much attention as a target for cancer chemoprevention. But meanwhile, constitutive Nrf2 activation in cancerous cells may promote cancer progression and resistance to chemotherapy. The current review describes the major underlying mechanisms involved in carcinogenesis of trace metals: copper, silver, and cadmium, with a special focus on the Nrf2 signaling pathway as a crossroad between oxidative stress and angiogenesis. [Display omitted] •Chronic metal exposure may be associated with different type of malignancies.•ROS generation has a major role in tumor angiogenesis and metal carcinogenicity.•Nrf2 is a master regulator of cellular response against HM-induced oxidative stresses.•Copper, cadmium, and silver have multiple effects on NrF2-signaling system.•Modulation of Cu, Cd and Ag effects in cancer prevention/treatment discussed.