Abstract
Hydrogen Sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H2S-mediated protein persulfidation and the detailed information about the dysregulation of H2S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H2S-mediated cancer progression and summarize current options to modulate H2S production for cancer therapy.
Highlights
Hydrogen sulfide (H2 S), a colorless, flammable, water-soluble gas, is recognized as the third gasotransmitter in 2002 [1]
Accumulated evidence indicates that dysregulation of these H2 S producing enzymes was observed in multiple cancer types (See Section 4), suggesting H2 S may play an important role during cancer development
Through H2 S-mediated persulfidation at Cys151, Kelch-like ECH-associated protein 1 (Keap1) can undergo a conformational change which leads to the dissociation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) from the Keap1-Cul3-RBX1 E3 ligase complex, and subsequently, the free Nrf2 translocates into the nucleus to exert its role on apoptosis escape [24,34,38,42,90]
Summary
Hydrogen sulfide (H2 S), a colorless, flammable, water-soluble gas, is recognized as the third gasotransmitter in 2002 [1]. Similar to the other two gasotransmitters, nitric oxide (NO) or carbon monoxide (CO), H2 S acts as a critical mediator in multiple physiological processes, including regulation of blood vessel vasodilation [2,3,4], cardiac response to ischemia/reperfusion injury [5], and inflammation [6]. Accumulated evidence indicates that dysregulation of these H2 S producing enzymes was observed in multiple cancer types (See Section 4), suggesting H2 S may play an important role during cancer development. In this review, we will summarize the current understanding of H2 S production, regulation, and biological functions during cancer development. We will focus on how H2 S-mediated protein persulfidation accomplishes cancer formation in different aspects of cancer hallmarks
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