肿瘤微环境
癌变
癌症
肿瘤进展
背景(考古学)
癌细胞
信号转导
肿瘤促进
癌症研究
肿瘤发生
细胞信号
生物
细胞生物学
肿瘤细胞
遗传学
古生物学
作者
João Agostinho Machado‐Neto,A Cerqueira,Sidney Veríssimo-Filho,Marcelo N. Muscará,Soraia K.P. Costa,Lucia Rossetti Lopes
标识
DOI:10.1089/ars.2021.0256
摘要
Significance: Cancer is a complex and heterotypic structure with a spatial organization that contributes to challenges in therapeutics. Enzymes associated with producing the gasotransmitter hydrogen sulfide (H2S) are differentially expressed in tumors. Indeed, critical and paradoxical roles have been attributed to H2S in cancer-promoting characteristics by targeting both cancer cells and their milieu. This review focuses on the evidence and knowledge gaps of H2S on the tumor redox microenvironment and the pharmacological effects of H2S donors on cancer biology. Recent Advances: Endogenous and pharmacological concentrations of H2S evoke different effects on the same cell type: physiological H2S concentrations have been associated with tumor development and progression. In contrast, pharmacological concentrations have been associated with anticancer effects. Critical Issues: The exact threshold between the promotion and inhibition of tumorigenesis by H2S is largely unknown. The main issues covered in this review include H2S-modulated signaling pathways that are critical for cancer cells, the potential effects of H2S on cellular components of the tumor microenvironment, temporal modulation of H2S in promoting or inhibiting tumor progression (similar to observed for inflammation), and pharmacological agents that modulate H2S and which could play a role in antineoplastic therapy. Future Directions: Given the complexity and heterogeneity of tumor composition, mechanistic studies on context-dependent pharmacological effects of H2S donors for cancer therapy are necessary. These studies must determine the critical signaling pathways and the cellular components involved to allow advances in the rational use of H2S donors as antineoplastic agents. Antioxid. Redox Signal. 40, 250–271.
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