Tariq Aziz

Adefovir anticancer potential: Network pharmacology, anti-proliferative and apoptotic effects in HeLa cells

Cervical cancer presents a significant healthcare challenge due to recurrent disease and drug resistance, highlighting the urgent need for novel therapeutic strategies. Network pharmacology facilitates drug repurposing by elucidating multi-target mechanisms of action. Adefovir, an acyclic nucleotide analog, has shown promising potential in cervical cancer treatment, particularly in HeLa cells. In vitro studies have demonstrated that adefovir inhibits HeLa cell proliferation by enhancing apoptosis while maintaining a low cytotoxicity profile at therapeutic concentrations, making it an attractive candidate for further exploration. A combined network pharmacology and in vitro study was conducted to investigate the molecular mechanism of adefovir against cervical cancer. Potential gene targets for adefovir and cervical cancer were predicted using database analysis. Hub targets were identified, and protein-protein interaction (PPI) networks were constructed. Molecular docking assessed adefovir's binding affinity to key targets. In vitro cytotoxic assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays, were performed using 96-well plates to evaluate anti-proliferative effects in HeLa cells. Apoptosis was assessed via p53 immunocytochemistry Enzyme-Linked Immunosorbent Assay (ELISA), while Vascular Endothelial Growth Factor ELISA (VEGF ELISA) was used to measure cell proliferation. Venn analysis identified 144 common targets between adefovir and cervical cancer. Network analysis revealed key hub targets involved in oncogenic pathways. Molecular docking demonstrated strong binding between adefovir and Mitogen-Activated Protein Kinase 3 (MAPK3) and SRC proteins. In vitro, adefovir significantly suppressed HeLa cell viability, with an Inhibitory Concentration 50 (IC50) of 7.8 µM, outperforming 5-Fluorouracil (5-FU). Additionally, it induced apoptosis via p53 activation and inhibited cell proliferation through VEGF suppression. These integrated computational and experimental findings suggest that adefovir exerts multi-targeted effects against cervical cancer. Its promising preclinical efficacy warrants further investigation as a potential alternative therapy.

The Prominence of the Broad-Spectrum Protease inhibitor gene A2ML1 as a potential biomarker in cervical cancer diagnostics using Immunotherapeutic and Multi-Omics approaches

One of the venereal tumors that threaten human life is cervical cancer. A2ML1 is detected in advanced-stage cancer patients and is found to be strongly associated with cervical cancer. A2ML1 was shown to be substantially expressed in cervical cancer in this study, which used data from the TCGA database. Those with high A2ML1 expression had a lower chance of survival than patients with low A2ML1 expression. Both univariate and multivariate Cox regression analyses were utilized to investigate the relationship between clinical variables and overall survival rates. An investigation into the link between A2ML1 and immune infiltration was subsequently conducted. Utilizing the immune cell database, research was conducted to investigate the dispersion of 24 immune cells and their correlation to A2ML1 expression. In addition to this, the favorable correlation between immune cells and A2ML1 was validated using all three immune cell methodologies. The Genomics of Drug Sensitivity in Cancer database was used to confirm the idea that there is a link between A2ML1 expression and the efficacy of chemotherapy or immunotherapy. The findings demonstrated that A2ML1 is a potential biomarker for cervical cancer diagnostics. This biomarker may be used to chaperone immunotherapy, as well as to explain the elucidates of cervical cancer caused by the immunological microenvironment.