Anjaly Km, Tiku Ashu Bhan
Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Prostate. 2025 Apr;85(5):463-470. doi: 10.1002/pros.24849. Epub 2025 Jan 2.
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.
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 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.
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.
咖啡酸（CA）是一种膳食化合物，其对抑制前列腺癌（PCa）生长的潜在影响已得到研究。PCa常与乙二醛酶-1（Glo-1）的高表达相关，这使其成为潜在治疗干预的靶点。CA抑制Glo-1表达的机制及其对PCa细胞增殖的影响是了解其作为抗癌剂潜力的研究热点。
通过MTT和克隆形成试验评估细胞活力和增殖。使用蛋白质印迹分析和免疫细胞化学评估特定蛋白质的表达水平。
结果表明，CA可显著降低PCa细胞增殖，同时诱导DNA双链断裂，通过降低前半胱天冬酶表达导致凋亡性细胞死亡。此外，发现CA可抑制Glo-1表达。为增强CA的抗癌效果，采用了一种将其与甲基乙二醛（MG）联合的新方法。外源性MG处理是一种糖酵解副产物和乙二醛酶底物，与CA联合时在PCa细胞中表现出剂量和时间依赖性毒性。这种联合治疗对PCa细胞显示出更高的毒性，这归因于CA对Glo-1表达的抑制和外源性MG的无毒剂量。因此，观察到内源性MG水平升高，导致细胞凋亡，提示这是一种靶向PCa中乙二醛酶致癌信号通路且副作用最小的有前景策略。
该研究突出了CA作为通过多种机制抑制PCa生长的治疗剂的潜力，包括诱导凋亡性细胞死亡和抑制Glo-1表达。将CA与MG联合可增强其抗癌效果，为靶向PCa中乙二醛酶致癌通路提供了一种有前景的策略。
