Probucol Exerts Anticancer Effects on SW480 Human Colorectal Cancer Cells via Modulation of Apoptosis‐ and Angiogenesis‐Related Proteins

Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the need for novel therapeutic agents with multitarget anticancer activity. Probucol is a phenolic compound with well-established antioxidant and anti-inflammatory properties; however, its effects on colorectal cancer cells have not been fully elucidated. The present study aimed to investigate the antitumor effects of probucol on SW480 human colorectal cancer cells and to explore the underlying molecular mechanisms focusing on cell cycle, apoptosis-, and angiogenesis-associated proteins. SW480 cells treated with probucol were subjected to MTT analysis. Cell cycle distribution and apoptosis were evaluated using cell cycle assay, Annexin V binding assay, and multicaspase activity assay. Apoptosis- and angiogenesis-related protein expression was analyzed by western blot, matrix metalloproteinase-9 (MMP-9) mRNA expression was quantified by real-time PCR. Probucol significantly reduced cell viability in a dose-dependent manner and induced cell cycle arrest at the G0/G1 phase. Treatment with probucol markedly increased early and late apoptotic cell populations and enhanced multicaspase activation. The upregulation of pro-apoptotic Bax protein was accompanied by downregulation of antiapoptotic Bcl-2. In addition, probucol significantly suppressed the expression of angiogenesis-associated proteins, including vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) and also decreased MMP-9 mRNA expression, indicating a potential antimetastatic effect. These findings demonstrate that probucol exerts significant anticancer effects on colorectal cancer cells by inhibiting cell proliferation, inducing apoptosis, and suppressing angiogenesis- and metastasis-related molecular markers. Probucol may represent a promising candidate for further investigation as a potential multitarget agent in colorectal cancer.