Exogenous Treatment of Caffeic Acid and Methylglyoxal Synergistically Enhances Anticancer Effect in Prostate Cancer via Inhibition of Glyoxalase-1.

Abstract

Background: Caffeic acid (CA), a dietary compound, has been studied for its potential impact on inhibiting prostate cancer (PCa) growth. PCa is often associated with heightened expression of glyoxalase-1 (Glo-1), making it a target for potential therapeutic interventions. CA's mechanisms in suppressing Glo-1 expression and its effects on PCa cell proliferation are areas of interest for understanding its potential as an anticancer agent.

Methods: Cellular viability and proliferation were evaluated through MTT and clonogenic assays. The expression levels of particular proteins were assessed using western blot analysis and immunocytochemistry.

Results: Results indicated significant reduction in PCa cell proliferation by CA, accompanied by induction of DNA double-strand breaks, leading to apoptotic cell death through decreased pro-caspases expression. Additionally, CA was found to inhibit Glo-1 expression. To enhance CA's anticancer effect, a novel approach was taken by combining it with methylglyoxal (MG). Exogenous MG treatment, a glycolysis by-product and glyoxalase enzyme substrate, exhibited dose and time-dependent toxicity in PCa cells when combined with CA. This combination treatment showed heightened toxicity against PCa cells, attributed to CA's inhibition of Glo-1 expression and the nontoxic doses of exogenous MG. Consequently, increased levels of endogenous MG were observed, leading to apoptosis and suggesting a promising strategy for targeting glyoxalase oncogenic signaling pathways in PCa with minimal adverse effects.

Conclusion: The study highlights the potential of CA as a therapeutic agent for inhibiting PCa growth through multiple mechanisms, including the induction of apoptotic cell death and inhibition of Glo-1 expression. Combining CA with MG enhances its anticancer effects, offering a promising strategy for targeting glyoxalase oncogenic pathways in PCa.