Enhanced Anticancer Effect by Combination of Proteoglucan and Vitamin K3 on Bladder Cancer Cells

Aim: Mushroom extract, PDF, is a bioactive proteoglucan with anticancer/antitumor activity, and Vitamin K3 (VK3) is a synthetic VK derivative with antitumor activity as well. An unconventional approach using these two agents was tested to see their anticancer effects on bladder cancer cells in vitro. Methods: Human bladder cancer T24 cells were treated with PDF, VK3, or their combination, and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To explore the anticancer mechanism, cell cycle and epigenetic alterations were specifically studied. Results: PDF ≥ 500 μg/mL led to a ~ 35% reduction in cell viability while VK3 had little effects. However, when PDF (300 μg/mL) was combined with VK3 (5 μM), a ~ 75% cell viability reduction was attained. This specific combination induced a G1 cell cycle arrest with the downregulation of G1-specific regulators. In addition, histone deacetylase was inactivated while histones 3 and 4 were highly acetylated. Two apoptotic regulators were significantly activated with PDF/VK3 combination as well. Conclusion: The specific combination of PDF and VK3 appears to potentiate anticancer effect on T24 cells. This is primarily attributed to a G1 cell cycle arrest with chromatin modifications, ultimately leading to apoptosis. Thus, the PDF/VK3 combination may offer a potential therapeutic option for bladder cancer.