Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells
Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells
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DOI：
10.1248/bpb.b15-01015
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发表时间：
2016-05-01
影响因子：
2
通讯作者：
Kawabata, Atsufumi
中科院分区：
文献类型：
--
作者：
Sekiguchi, Fumiko;Sekimoto, Teruki;Kawabata, Atsufumi
硫化氢（H2S）是第三种气体递质，由哺乳动物体内某些H2S合成酶（包括来自L-半胱氨酸的胱硫醚-γ-裂解酶（CSE）和胱硫醚-β-合成酶（CBS））内源性产生。几项研究表明，内源性和外源性H2S影响癌细胞的增殖，尽管H2S的作用似乎随细胞类型而变化，是促进性的或抑制性的。在本研究中，我们确定是否内源性形成H2S调节人胃癌AGS细胞的增殖。CSE在AGS细胞中表达，而CBS不表达。CSE抑制剂DL-炔丙基甘氨酸（PPG）和β-氰基-L-丙氨酸（BCA）以浓度依赖性方式显著抑制AGS细胞的增殖。CSE抑制剂在相同浓度范围内不增加乳酸脱氢酶（LDH）释放。PPG和BCA对细胞增殖的抑制作用可被重复应用NaHS（H2S的供体）逆转。有趣的是，在用PPG或BCA处理的AGS细胞中检测到核浓缩和碎裂。这些结果表明CSE产生的内源性H2S可能有助于胃癌AGS细胞的增殖，最可能是通过抗凋亡作用。
Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and beta-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.