Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025048
As a classic tumor suppressor gene, p53 has been extensively studied since its discovery in the mid-1980s. Research findings have revealed that p53 protein expression is suppressed in various cancers [1]. For example, in cervical cancer, p53 predominantly exists in a wild-type form to maintain its biological function [2]. Nevertheless, its tumor-suppressive activity is significantly impaired because of rapid protein degradation, short half-life, and low levels. Post-translational modifications (PTMs) of p53, such as ubiquitination, acetylation, phosphorylation and methylation, are critical regulators of its stability, activity, conformation, localization, and interactions with cofactors [3]. Among these, ubiquitination and acetylation play central roles in controlling p53 protein stability and activity [4]. Therefore, targeting p53 PTMs to modulate its ubiquitination and acetylation levels represents an effective strategy to increase its stability and tumor-suppressive function, offering a promising avenue for cervical cancer drug development. In 99% of cervical cancers (high-risk human papillomavirus-positive), E3 ubiquitin ligase E6-associated protein (E6AP) mediates the ubiquitination degradation of p53 [5], whereas histone deacetylase 6 (HDAC6) deacetylates p53. In this study, we explored the possibility of combining the natural product withferin A (WA) with the HDAC6 inhibitor ricolinostat (RIC) to treat cervical cancer cells, with a focus on the ubiquitination and acetylation of p53 and the consequences for its stability. These results suggested that the combination of WA and RIC is more effective than either treatment alone in inhibiting the degradation and increasing the stability of p53, thereby synergistically slowing the onset and progression of cervical cancer.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261505
This study systematically evaluated the impact of three processing methods—fire treatment, dry distillation, and water boiling—on the chemical composition and antitussive/expectorant efficacy of Bambusae Succus (BS). GC-MS analysis quantified guaiacol and syringol contents: fire treatment yielded 4.68% and 2.22% respectively, with total phenolics at 14.93%; dry distillation yielded 5.98% and 6.96%, with total phenolics at 24.77%; water boiling produced total phenolics of 3.65%, with both target compounds below detection limits. PCA and OPLS-DA identified 13 discriminatory components, including 2-methylphenol, creosol, eugenol, and vanillin. Microscopic examination revealed that water boiling preserved bamboo microstructure similar to fresh bamboo, whereas fire treatment and dry distillation induced significant structural degradation. In a COPD mouse model, all three preparations exhibited antitussive and expectorant effects, but dry distillation significantly prolonged cough latency (P<0.05) and increased phenol red excretion (P<0.01). The superior efficacy of dry distillation is attributed to its higher retention and thermal conversion of lignin-derived phenolics, specifically 4-ethylguaiacol and maltol, which modulate Nrf2/HO-1 and NF-κB pathways. These findings establish dry distillation as the optimal processing method for maximizing bioactive phenolic content and therapeutic efficacy, providing a scientific basis for clinical application and new formulation development.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025048
Cervical cancer remains a leading cause of cancer-related mortality among women, with high-risk HPV-positive cases constituting 99% of instances. Despite wild-type p53 expression, its tumor-suppressive function is crippled by E6AP-mediated ubiquitination and HDAC6-driven deacetylation, resulting in rapid degradation and low steady-state levels. This study evaluates a combinatorial strategy employing the natural product withaferin A (WA) and the HDAC6 inhibitor ricolinostat (RIC) to simultaneously target p53 ubiquitination and acetylation in HeLa, SiHa, and Caski cervical cancer cells. Dose-response CCK-8 assays established that both agents inhibit proliferation in a dose-dependent manner. Combination treatment significantly reduced cell viability compared to monotherapies, with CompuSyn analysis yielding a combination index (CI) below 1, confirming synergy. Colony formation assays further demonstrated a marked decrease in clonogenic survival. Mechanistically, WA disrupted the p53-E6AP interaction, reducing p53 ubiquitination, while RIC inhibited HDAC6-mediated deacetylation, increasing p53 acetylation. The dual treatment stabilized p53, as evidenced by extended half-life in cycloheximide chase assays. These findings suggest that concurrent modulation of p53 post-translational modifications via WA and RIC offers a potent therapeutic avenue for cervical cancer, meriting further preclinical development.