Withaferin A combined with ricolinostat: a potent synergistic therapy for cervical cancer through regulating p53 ubiquitination and acetylation

• The combination of Withaferin A (WA) and ricolinostat (RIC) synergistically inhibits cervical cancer cell proliferation and colony formation in vitro, with a combination index (CI) < 1. • In vivo, the WA+RIC combination significantly reduces tumor volume and weight in a HeLa xenograft mouse model compared to single-agent treatments. • The synergistic effect is attributed to enhanced p53 stability via inhibition of ubiquitination (by WA) and acetylation (by RIC), restoring p53 tumor-suppressive function. • This study provides a promising therapeutic strategy for cervical cancer, particularly for HPV-positive cases where p53 is degraded by E6AP.