• • Combination of WA and RIC yields a combination index (CI) < 1 in HeLa, SiHa, and Caski cells, indicating synergistic inhibition of cell viability; this synergy is critical for reducing effective doses and minimizing off-target toxicity in clinical settings.
• • WA treatment for 24 h disrupts the p53-E6AP interaction, decreasing p53 ubiquitination; this directly addresses the primary degradation pathway in HPV-positive cervical cancer, potentially restoring p53 tumor-suppressive function.
• • RIC treatment for 24 h inhibits HDAC6-mediated deacetylation, increasing p53 acetylation; elevated acetylation enhances p53 stability and transcriptional activity, a mechanism that complements ubiquitination blockade.
• • The combination extends p53 half-life beyond 60 min in cycloheximide chase assays, compared to rapid degradation in controls; this sustained stabilization is essential for mounting an effective apoptotic response and overcoming the short half-life bottleneck of wild-type p53 in cervical cancer.