Anticancer activity of polycarpol from Uvaria siamensis roots against human cervical cancer cells in nude mouse xenograft models
Komsil Pholdaeng, Ratsami Lekphrom, Florian T. Schevenels, Gulsiri Senawong, Arunta Samankul, Narissara Namwan, Pitchakorn Sangchang, Thanaset SenawongBackground 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
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.
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.