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目的:探讨了木犀草素对酪氨酸酶的抑制作用和诱导黑色素瘤细胞凋亡机制。方法:本文采用酶抑制动力学方法,对木犀草素诱导酪氨酸酶活性降低的机制进行了研究,并结合分子模拟和螯合铜离子实验初步探讨了木犀草素与酪氨酸酶的结合机理,最后进行了黑色素瘤细胞A375的生长抑制试验。结果:木犀草素对酪氨酸酶具有良好的抑制作用(半抑制浓度IC50为51.54±3.42μmol/L);通过螯合铜离子实验发现,木犀草素能够与酪氨酸酶的活性中心铜离子发生结合作用;分子模拟结果表明,木犀草素能够优先结合到酪氨酸酶的活性中心Cu离子附近,并与催化基团His85形成氢键;木犀草素能够明显的诱导A375的凋亡,且细胞中的酪氨酸酶活性和黑色素的合成量降低。结论:木犀草素作为一种酪氨酸酶抑制剂,诱导了酶活性的降低和黑色素瘤的凋亡,对调节黑色素水平起到重要作用。
Objective: To investigate the inhibition of tyrosinase by luteolin and the mechanism of apoptosis in melanoma cells. Methods: In this paper, enzyme-inhibition kinetics was used to study the mechanism of the decrease of tyrosinase activity induced by luteolin. The combination of luteolin and tyrosinase was also studied by molecular simulation and chelation of copper ion Mechanism, and finally the melanoma A375 cell growth inhibition test. Results: Luteolin had a good inhibitory effect on tyrosinase (IC50 was 51.54 ± 3.42μmol / L). It was found by chelation of copper ion that luteolin could interact with the active center of tyrosinase Ion binding. The results of molecular modeling showed that luteolin could preferentially bind to the Cu ion near the active site of tyrosinase and form a hydrogen bond with the His85 catalytic group. Luteolin could obviously induce the apoptosis of A375, And the amount of tyrosinase activity and melanin synthesis in the cells is reduced. Conclusions: Luteolin, as a tyrosinase inhibitor, induces a decrease in enzyme activity and apoptosis in melanoma and plays an important role in the regulation of melanin levels.