木犀草素诱导黑色素瘤细胞凋亡机制的探讨

Study the apoptosis mechanism of tyrosinase inhibitor luteolin on melanoma cell

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。

Purpose： Study of the inhibitory effect of luteolin on tyrosinase and the apoptosis mechanismon melanoma cells. Methods： The inhibitory effect of tyrosinase induced by luteolin was investigated. and the interation mechanism of luteolin on tyrosinase was preliminarily indicated by Molecular simulation and chelating copper ions,and A375 melanoma cell growth inhibition was mensured. Results： Luteolin had a good inhibitory effect on tyrosinase（ its half inhibition concentratio IC50 was obtained to be 51. 54 ± 3. 42 μmol / L）. Chelating copper ions and molecular simulation further showed that luteolin was combined with active center of copper ions,and formed hydrogen bonds with catalytic site His85. Luteolin could induce the apoptosis of A375 cells significantly,and the tyrosinase activity and melanin synthesis were decreased.Conclusion： Luteolin as a tyrosinase inhibitor,played an important role in the regulation of melanin,which provides the theoretical basis for the clinical anti skin cancer.