A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

作者：Xu Cao, Lei Ding, Zhizhong Xie, Yong Yang, Matthew Whiteman, Philip Keith Moore, Jin‐Song Bian · 发表于：Antioxidants and Redox Signaling · 年份：2018 · DOI：10.1089/ars.2017.7058 · 被引用次数：412 · 研究领域：Sulfur Compounds in Biology、Glutathione Transferases and Polymorphisms、Genomics, phytochemicals, and oxidative stress

Significance: Hydrogen sulfide (H 2 S) has been recognized as the third gaseous transmitter alongside nitric oxide and carbon monoxide. In the past decade, numerous studies have demonstrated an active role of H 2 S in the context of cancer biology. Recent Advances: The three H 2 S-producing enzymes, namely cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), have been found to be highly expressed in numerous types of cancer. Moreover, inhibition of CBS has shown anti-tumor activity, particularly in colon cancer, ovarian cancer, and breast cancer, whereas the consequence of CSE or 3MST inhibition remains largely unexplored in cancer cells. Intriguingly, H 2 S donation at high amounts or a long time duration has also been observed to induce cancer cell apoptosis in vitro and in vivo while sparing noncancerous fibroblast cells. Therefore, a bell-shaped model has been proposed to explain the role of H 2 S in cancer development. Specifically, endogenous H 2 S or a relatively low level of exogenous H 2 S may exhibit a pro-cancer effect, whereas exposure to H 2 S at a higher amount or for a long period may lead to cancer cell death. This indicates that inhibition of H 2 S biosynthesis and H 2 S supplementation serve as two distinct ways for cancer treatment. This paradoxical role of H 2 S has stimulated the enthusiasm for the development of novel CBS inhibitors, H 2 S donors, and H 2 S-releasing hybrids. Critical Issues: A cle...