Hydrogen Sulfide Signaling in the Tumor Microenvironment: Implications in Cancer Progression and Therapy

Autor(es)

Machado-Neto, Joao Agostinho ; Cerqueira, Anderson Romerio Azevedo ; Verissimo-Filho, Sidney ; Muscara, Marcelo Nicolas ; Costa, Soraia Katia Pereira ; Lopes, Lucia Rossetti

• Tipo de documento: Artigo Científico
• Fonte: Antioxidants & Redox Signaling; v. 40, n. 4-6, p. 22-pg., 2023-09-22.

Resumo

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. (AU)

• Processo FAPESP: 20/12432-6 - Investigação dos mecanismos redox dependentes envolvidos na resistência ao Vemurafenibe em células de Melanoma
• Beneficiário: Lucia Rossetti Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/06146-5 - Biodisponibilização do sulfeto de hidrogênio em nanoformulação tópica e sua eficácia na psoríase experimental
• Beneficiário: Soraia Katia Pereira Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/23864-7 - Análise compreensiva de dados genômicos para identificação e validação de novos alvos terapêuticos envolvidos na regulação de citoesqueleto celular em Leucemias agudas
• Beneficiário: João Agostinho Machado Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs