Anticancer activity of polycarpol from Uvaria siamensis roots against human cervical cancer cells in nude mouse xenograft models

Background and purpose: Cervical cancer treatment with cisplatin or 5-fluorouracil is often hindered by resistance and toxicity. This study aimed to investigate the mechanisms underlying polycarpol's antiproliferative activity in vitro and its potential anticancer effects in vivo . Experimental approach: Cell cycle arrest was evaluated by PI staining, and apoptosis was determined by Annexin V-FITC/PI staining, followed by flow cytometric analysis. In vivo antitumor activity was evaluated using TGI% in nude mouse xenograft models. Survival rate, BWC%, and hematoxylin and eosin staining were used to assess toxicity in nude mouse xenograft models. Findings/Results: Polycarpol (25-50 μM) caused G2/M phase cell cycle arrest only after 24 h of exposure. In addition, polycarpol (25-200 μM) caused concentration- and time-dependent increases in the sub-G1 population, indicating apoptosis. Annexin V-FITC apoptosis assay confirmed that polycarpol (25-200 μM) caused a concentration-dependent increase in apoptotic HeLa cells at 24 h and a time-dependent increase across all tested concentrations at 24-72 h. In nude mouse xenograft models, polycarpol (50-100 mg/kg) significantly suppressed tumor growth, with the highest dose (100 mg/kg) showing the greatest effect compared with the vehicle control group. Polycarpol (50-100 mg/kg) showed no toxicity to the liver or kidneys; however, the 100 mg/kg dose caused spleen toxicity in a mouse model. Conclusion and implications: Polycarpol may inhibit cervical cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis, suggesting its potential as an anticancer drug.