Tahir Maqbool

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.

Synergistic Effect of Barbadensis miller and Marsdenia Condurango Extracts Induces Apoptosis Promotes Oxidative Stress by Limiting Proliferation of Cervical Cancer and Liver Cancer Cells

Drug synergy is the combine effect of drug efficacy. Synergistic combinations of active ingredients have proven to be highly effective and more useful in therapeutics. In contrast, the individual effect of drug is usually undesirable and mostly used for selecting drug-resistant mutations. Purpose of this study was to check synergistic effects of both plants (Barbadensis miller and Marsdenia condurango) against liver and cervical cancer. Culturing of HeLa (cervical cancer cell line) and HepG2 (liver cancer cell line) cells, IC50 evaluation, viability assays (trypan blue, crystal violet), p53 ELISA and immunocytochemistry, MUSE analysis (count and viability), antioxidants (GSH, SOD, CAT), at the end RT-PCR was performed. IC50 evaluation was done of each plant individually and with combination for synergistic effects, IC50 with plants combination (synergism) was applied on further viability assays (trypan blue, crystal violet, MUSE analysis via count and viability kit) p53 ELISA and immunocytochemistry for evaluation of cellular apoptosis, antioxidants assays (GSH, SOD, CAT), and RT-PCR with proliferative and apoptotic markers along with internal control. According to current study it was observed that synergistic effect of these plants has more anticancer properties with minimum effective dose. It was also observed that extracts possess the ability to induce apoptosis, restrict proliferation and enhanced oxidative stress.