pomolic-acid and Prostatic-Neoplasms

Prostate cancer (PC) is one of the leading causes of cancer‑related death in the male population worldwide. Mortality of PC is dependent on tumor recurrence and its progression to metastatic disease. We examined the effects of pentacyclic triterpene pomolic acid (PA) on docetaxel‑resistant PC3 cells. Cell viability was evaluated using the MTT assay. Apoptosis was evaluated by cell cycle analysis using flow cytometry. The activity of multiple drug resistance (MDR) proteins was determined by the accumulation of specific substrates [mitoxantrone, rhodamine 123 and 5‑carboxyfluorescein diacetate (CFDA)]. The evaluation of epithelial to mesenchymal transition (EMT) proteins was conducted by immunocytochemical assays. It was demonstrated that PC3R cells presents multidrug resistance and EMT phenotype and express active P‑gp/ABCB1 and MRP1/ABCC1. It was shown that PA strongly reduced the viability and induced apoptosis of both PC3 and PC3R cell lines. Moreover, PA bypassed P‑gp/ABCB1, downmodulated MRP1/ABCC1 activities, and partially reverted EMT induced by DTX. Our goal was to evaluate the potential of PA for the development of novel strategies to treat castration‑resistant PC.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cell Survival; Docetaxel; Drug Resistance, Neoplasm; Drug Synergism; Epithelial-Mesenchymal Transition; Humans; Male; Multidrug Resistance-Associated Proteins; Oleanolic Acid; Prostatic Neoplasms