Molecular Basis of Biochanin A-Induced Inhibition in Gastric Cancer AGS Cells
Xue-Wei Hao, Quan Quan, Nan Wu, Xi-Chun Huang, Jun-Hao Li, Ying-Hua Luo, Yan-Liang Zhang, Cheng-Hao JinIntroduction:
Biochanin A (BCA) has demonstrated anti-inflammatory and anticancer activities in previous pharmacological studies; however, its specific mechanisms of action against various Gastric Cancer (GC) subtypes remain unclear. In this study, the molecular mechanisms underlying its effects against AGS cells were systematically investigated.
Methods::
The CCK-8 assay was used to screen for the most sensitive GC cell line. Apoptosis, cell cycle progression, and migration/invasion rates were quantified using flow cytometry, Transwell assays, and woundhealing assays. The activation of the MAPK/STAT3/NF-κB, AKT, and Wnt/β-catenin axes was examined via western blotting. Intracellular ROS production was quantified using a DCFH-DA probe, and N-acetyl-Lcysteine (NAC) served as a scavenger to confirm the functional role of ROS.
Results:
BCA exhibited the lowest IC50 among the tested compounds in AGS cells. This effect was characterized by apoptosis, accompanied by mitochondrial depolarization. Meanwhile, BCA treatment led to the upregulation of markers associated with apoptosis, G2/M phase arrest, and the reduction in migration/invasion rates. These effects were partially attenuated by NAC, supporting a contributory role for ROS as an upstream mediator.
Discussion:
This study provides molecular evidence that ROS acts as an upstream mediator regulating apoptosis, cell cycle arrest, and reduced migration/invasion, suggesting BCA may similarly affect cancer subtypes with these pathways and merits further investigation.
Conclusion:
BCA harnesses ROS as an upstream mediator of three major signaling axes to exert its anti-AGS effects, providing a mechanistic basis for further evaluation of BCA in GC models.