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4-甲基亚磺酰基-3-丁烯基异硫氰酸酯是从萝卜中分离出的抗肿瘤单体化合物。本研究主要探讨了4-甲基亚磺酰基-3-丁烯基异硫氰酸酯对人非小细胞肺癌A549细胞增殖、凋亡的影响及其与微管蛋白的作用模式。结果发现,4-甲基亚磺酰基-3-丁烯基异硫氰酸酯可以有效抑制A549细胞增殖,并能诱导其凋亡,呈剂量依赖关系。分子对接研究结果表明,4-甲基亚磺酰基-3-丁烯基异硫氰酸酯与由Ala314、Cys315、Cys316、Gly350、Phe351、Lys352、Cys347、Pro348和Phe343等氨基酸残基组成的亲脂性活性口袋中的Cys347以共价键结合,并与Lys352以氢键结合。因此,4-甲基亚磺酰基-3-丁烯基异硫氰酸酯通过与微管蛋白以共价键和氢键形式结合,来抑制微管蛋白聚合并诱导A549细胞凋亡。
4-Methylsulfinyl-3-butenyl isothiocyanate is an anti-tumor monomeric compound isolated from radish. In this study, we investigated the effects of 4-methylsulfinyl-3-butenyl isothiocyanate on proliferation and apoptosis of human non-small cell lung cancer A549 cells and their interaction with tubulin. The results showed that 4-methylsulfinyl-3-butenyl isothiocyanate can effectively inhibit A549 cell proliferation and induce apoptosis in a dose-dependent manner. The results of molecular docking showed that the affinity of 4-methylsulfinyl-3-butenyl isothiocyanate with an amino acid residue consisting of Ala314, Cys315, Cys316, Gly350, Phe351, Lys352, Cys347, Pro348 and Phe343 Cys347 in the lipophilic active pocket binds covalently and hydrogen bonds to Lys352. Thus, 4-methylsulfinyl-3-butenyl isothiocyanate inhibits tubulin polymerization and induces apoptosis in A549 cells by covalently and hydrogenically bonding with tubulin.