BAMLET (Bovine α-lactalbumin made lethal to tumor cells) inhibits autophagy flux and induces apoptosis via down-regulation of protein kinase CK1α and attenuation of the AKT/p-ß-catenin (S552) pathway in RAS-mutated human colorectal HCT 116 cells

BAMLET(对肿瘤细胞具有致死作用的牛 α-乳白蛋白)可抑制自噬通量,并通过下调蛋白激酶 CK1α 和减弱 RAS 突变的人类结肠直肠癌 HCT 116 细胞中的 AKT/p-β-catenin (S552) 通路来诱导细胞凋亡

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作者:Hamid Behrouj, Pooneh Mokarram

Conclusion

BAMLET hampers autophagy flux and leads to apoptosis induction, possibly, by reducing the expression of CK1α and attenuation of the AKT/Phospho-ß-catenin (S552) axis.

Methods

For this purpose, HCT116 cells were treated with BAMLET and casein kinase 1 inhibitor (D4476), and quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to measure the proteins and genes of the AKT/Phospho-ß-catenin (S552) pathway and autophagy. Apoptosis was measured by flow-cytometry.

Results

We found that BAMLET significantly reduced cell viability and decreased the expression of CK1α. Additionally, BAMLET inhibited autophagy flux and enhanced the ability of CK1α inhibitor D4476 to impair autophagy flux, which was accompanied by an increase in the apoptosis percentage. We also observed that BAMLET empowered D4476 to down-regulate the AKT/Phospho-ß-catenin (S552) axis.

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