Hellmich Mark R, Coletta Ciro, Chao Celia, Szabo Csaba
1 Department of Surgery, University of Texas Medical Branch , Galveston, Texas.
Antioxid Redox Signal. 2015 Feb 10;22(5):424-48. doi: 10.1089/ars.2014.5933. Epub 2014 Jun 20.
Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways.
In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H2S) from cystathionine β-synthase (CBS) plays an important role in promoting the cellular bioenergetics, proliferation, and migration of cancer cells. It also stimulates peritumor angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both in vitro and in vivo, and potentiates the antitumor efficacy of anticancer therapeutics.
Recently published studies are reviewed, implicating CBS overexpression and H2S overproduction in tumor cells as a tumor-growth promoting "bioenergetic fuel" and "survival factor," followed by an overview of the experimental evidence demonstrating the anticancer effect of CBS inhibition. Next, the current state of the art of pharmacological CBS inhibitors is reviewed, with special reference to the complex pharmacological actions of aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile a controversy in the literature regarding the effects of H2S donor on cancer cell proliferation and survival.
From a basic science standpoint, future directions in the field include the delineation of the molecular mechanism of CBS up-regulation of cancer cells and the delineation of the interactions of H2S with other intracellular pathways of cancer cell metabolism and proliferation. From the translational science standpoint, future directions include the translation of the recently emerging roles of H2S in cancer into human diagnostic and therapeutic approaches.
癌症是一个重大的社会经济问题；迫切需要针对肿瘤特异性途径的新型治疗方法。
在结直肠癌和卵巢癌中，胱硫醚β-合酶（CBS）使肿瘤内硫化氢（H2S）生成增加，这在促进癌细胞的细胞生物能量学、增殖和迁移中起重要作用。抑制CBS的表达或基因沉默在体外和体内均具有抗肿瘤作用，还能增强抗癌治疗药物的抗肿瘤疗效。
本文回顾了最近发表的研究，这些研究表明肿瘤细胞中CBS的过表达和H2S的过量产生是促进肿瘤生长的“生物能量燃料”和“生存因子”，接着概述了证明抑制CBS具有抗癌作用的实验证据。然后，回顾了药理学上CBS抑制剂的当前技术水平，特别提及了氨氧乙酸的复杂药理作用。最后，提出了新的实验证据，以解决文献中关于H2S供体对癌细胞增殖和存活影响的争议。
从基础科学的角度来看，该领域未来的方向包括阐明癌细胞中CBS上调的分子机制，以及阐明H2S与癌细胞代谢和增殖的其他细胞内途径之间的相互作用。从转化科学的角度来看，未来的方向包括将H2S在癌症中最近出现的作用转化为人类诊断和治疗方法。
