Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

The role of hydrogen sulphide (H2S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H2S‐induced angiogenesis. H2S promotes angiogenesis by upregulating VEGF via pro‐angiogenic signal transduction. The involved signalling pathways include the mitogen‐activated protein kinase pathway, phosphoinositide‐3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)‐sensitive potassium (KATP) channels. H2S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H2S can exert an anti‐angiogenic effect by inactivating Wnt/β‐catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H2S plays a double‐edged sword role in the process of angiogenesis. The regulation of H2S production is a promising therapeutic approach for angiogenesis‐associated diseases. Novel H2S donors and/or inhibitors can be developed in the treatment of angiogenesis‐dependent diseases.

Hydrogen sulfide (H2S) has been widely recognized as one of gasotransmitters. Endogenous H2S plays a crucial role in the progression of cancer. However, the effect of endogenous H2S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine‐β‐synthase), dl‐propargylglycine (PAG, an inhibitor of cystathionine‐γ‐lyase), and l‐aspartic acid (l‐Asp, an inhibitor of 3‐mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2S in NPC growth. The results indicated that the combine (PAG + AOAA + l‐Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l‐Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)‐extracellular signal‐regulated protein kinase but higher expressions of p‐p38 and p‐c‐Jun N‐terminal kinase than those in the AOAA, PAG, and l‐Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2S generation could dramatically inhibit NPC growth via the ROS/mitogen‐activated protein kinase pathway. Endogenous H2S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2S‐producing enzymes could be designed and developed for NPC treatment.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine β-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), β-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/β-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

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