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(1) Ferulic acid significantly suppress the proliferation and migration of colon cancer cells at various Duke's stages.
(2) Ferulic acid holding SW-480 and Caco-2 cells at S-stage, while HCT-116 cells at G1-stage, and ultimately cause cell apoptosis.
(3) The inhibition capability is associated with the activation of ATR/Chk1 or ATM/Chk2 pathways by ferulic acid.
Ferulic acid is a widely distributed phenolic acid in plants and herbs, often conjugates with large molecules and enters the colon to exert anti-cancer effect. However, its suppression effect and mechanisms of action on colon cancer cells across various stages of Duke’s classification is not clear. This study aims to investigate the effects of ferulic acid on the migration, cell cycle, apoptosis, and signaling pathways in colon cancer cells (SW-480, Caco-2, and HCT-116) at different Duke’s stages. Results demonstrates that ferulic acid significantly inhibits the proliferation and migration of these cells, inducing cell cycle arrest at different phase, and ultimately promotes apoptosis in a dose-dependent manner. Specifically, ferulic acid activates the ATM/Chk2 and ATR/Chk1 pathways, down regulating their relative cell cycle regulatory proteins (CDK2 and Cyclin A2 complex, CDK4/6 and Cyclin D1/E1 complex), and thus leading to S-phase arrest in SW-480 and Caco-2 cells, and G1 phase arrest in HCT-116 cells, respectively. In addition, upregulated p53 and p21 proteins also contributing to the induction of apoptosis. This study is highly significant as they provide a deeper understanding of the molecular mechanisms by which ferulic acid exerts its anticancer effects at different Duke’s stages, and propose novel dietary strategy for the prevention of colon cancer.
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