BRAF inhibitor candidate molecule usnic acid might use both intrinsic and extrinsic pathways of apoptosis

BRAF 抑制剂候选分子松萝酸可能同时使用内在和外在的凋亡途径

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作者:Burcu Pelin Büyük, Demet Cansaran Duman, Türker Duman

Aim

Melanoma is one of the most aggressive cancers and treatment

Conclusion

As a result of the obtained findings, it could be concluded that UA might be a promising candidate drug molecule for melanoma treatment in the future through topical application or encapsulation with nanocarriers.

Methods

To determine the cell death pathway through which UA exerts its antiproliferative effect, its potential for apoptotic effects was investigated. Caspase-3 and caspase-9 enzyme assays and the expression analysis of 84 genes from the apoptosis pathway were carried out in UA-treated and nontreated A-375 cells.

Results

UA was found to have an antiproliferative effect on A-375 cells while it did not have a cytotoxic effect on human epidermal melanocytes. UA treatment led to statistically significant increases in both caspase-3 and caspase-9 enzyme activities. Moreover, the expression levels of 61 genes (mainly proapoptotic genes) were increased and the expression levels of 23 genes (mainly antiapoptotic genes) were decreased in response to UA treatment. This effect might have developed through both the extrinsic and intrinsic apoptosis pathways; however, the extrinsic pathway was more pronounced.

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