Research Article

Aesculetin Inhibits Proliferation and Induces Mitochondrial Apoptosis in Bladder Cancer Cells by Suppressing the MEK/ERK Signaling Pathway

Author(s):

Li Han, Peiwu Li, Xu Fu, Zhenzhen Huang and Wen Yin*   Pages 478 - 487 ( 10 )

Abstract:

<p>Background: Aesculetin (AE), a natural coumarin derivative found in traditional medicinal herbs, has a variety of pharmacological effects. However, the role of AE and its molecular mechanisms of action on bladder cancer remains undefined. <p> Objective: The study aims to explore the anti-tumor effects of AE on bladder cancer cells and the associated molecular mechanisms. <p> Methods: We performed a Cell Counting Kit-8 assay to examine the inhibitory effects of AE on 5637 and T24 cells. The anti-tumor effects of AE on 5637 cells were evaluated by performing colony formation, living/dead cell staining, apoptosis, cell cycle, migration and invasion assays. The expression levels of related proteins were determined using western blotting. <p> Results: The viability of 5637 and T24 cells was decreased by AE. AE significantly inhibited colony formation, arrested the cell cycle at the G0/G1 phase, decreased migration and invasion, decreased the mitochondrial membrane potential and increased apoptosis in 5637 cells. Western blotting results showed the release of cytochrome C from mitochondria; the activation of caspase-9 and caspase-3; decrease in CDK4, CCND1, MMP2 and MMP9 levels and an increase in the BAX/BCL-2 protein ratio after treatment with AE. AE also downregulated the levels of p-ERK and p- MEK proteins. Pre-treatment with U0126 significantly enhanced the anti-tumor effects of AE. <p> Conclusions: AE inhibited the proliferation and induced the apoptosis of bladder cancer cells through the MEK/ERK pathway. These findings provide possible therapeutic strategies for bladder cancer.</p>

Keywords:

Bladder cancer, aesculetin, MEK/ERK, proliferation, apoptosis, migration and invasion.

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