腐植酸和黄腐酸诱导酪氨酸酶的热力学和结构不稳定性对A375黑色素瘤癌细胞的抗增殖作用

Negar Taherkhani, Hossein Piri, A. Hekmat, K. Haghbeen
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引用次数: 0

摘要

背景:酪氨酸酶通过黑色素形成过程催化单酚类物质生成黑色素。因此,在食品和化妆品行业中,人们研究了各种抑制剂对黑色素生成异常的酶调节。本研究研究了腐植酸(Hu)和黄腐酸(Fu)对蘑菇酪氨酸酶(MT)结构、活性和稳定性的影响。方法:这两种有机酸是土壤腐殖质的主要成分。通过化学变性和热变性以及(8-苯胺-萘磺酸)ANS荧光分析对酶的热力学和结构稳定性进行了评价。通过MTT法测定Hu和Fu对A375黑色素瘤癌细胞活力的影响。结果:酶半变性浓度(Cm)、熔点(Tm)、ΔG0值和在Hu和FA存在下的外部荧光发射结果证明,这些化合物降低了MT的热力学和结构稳定性。通过Hu和Fu对A375黑色素瘤细胞系处理24和48小时时,31.5和42.7µM、12.5和µM的抑制浓度分别为50% (IC50),证实了化合物的抗增殖作用。结论:腐植酸和黄腐酸有望推动皮肤病科学的发展,在酪氨酸酶相关疾病和抗癌方面发挥重要作用,具有良好的医学应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Humic and Fulvic Acids Induced Thermodynamic and Structural Instability of Tyrosinase With Antiproliferative Effect on A375 Melanoma Cancer Cell Line
Background: The tyrosinase enzyme catalysis monophenols to melanin pigments through the melanogenesis process. For this reason, various inhibitors have been studied for enzyme regulations in melanogenesis abnormalities in both the food and cosmetics industries. In this study, the effect of humic acid (Hu) and fulvic acid (Fu) on the structure, activity, and stability of mushroom tyrosinase (MT) was investigated. Methods: These two organic acids are the main components of soil humus. Assessment of the thermodynamic and structural stability of enzymes was obtained through thechemical and thermal denaturations and (8-anilino-naphthalene sulfonic acid) ANS fluorescence analysis. The Hu and Fu impact on A375 melanoma cancer cell viability was achieved by MTT assay. Findings: The results of enzyme half denaturation concentration (Cm), melting points (Tm), ΔG0 values and external fluorescence emissions in the presence of Hu and FA proved the reduction of the thermodynamic and structural stability of MT by these compounds. The anti-proliferation effects of the compounds were confirmed by the inhibitory concentrations of 50% (IC50) of 31.5 and 42.7 µM and 12.5 and µM at time points of 24 and 48 hours treatments of the A375 melanoma cell line by Hu and Fu, respectively. Conclusion: Humic and fulvic acids can be expected to contribute to advancing skin disorder science play a crucial role in tyrosinase related disorders and anti-cancer effects, and good candidates for medical applications.
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