Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines

Introduction: Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research. Methods: Differentially expressed genes (DEGs) and survival-associated DEGs (SDEGs) were identified using the GEPIA2 database through the TCGA-CESC dataset. The 3D structures of target proteins were predicted using trRosetta and validated via SAVES v6.0. Phytocompounds were retrieved from the PubChem database, and docking studies were performed using AutoDock Vina. The miRNAs regulating HK2 and MAP7 were also predicted by implementing miRNetv2.0 and the CancerMIRNome database. Finally, the anticancer activity of these compounds was validated individually and in combination using the ME180 and SiHa CC cell lines. Results: The present study identified the top five most hazardous novel biomarkers through DEGs (5763) and SDEGs (500) (P-value ≤ 0.05). The phytocompounds EGCG and myricetin interacted with HK2 with binding affinities of -8.3 and -8.1 kcal/mol and RMSDs of 1.369Å and 1.452Å, respectively. Similarly, EGCG (-9.1 kcal/mol) and myricetin (-7.9 kcal/mol), with the RMSD of 1.682Å and 1.148Å, showed strong bonding with the MAP7. EGCG and myricetin treatment synergistically inhibited ME180 (IC50 = 63.49μM) and SiHa (IC50 = 81.54μM) cell-proliferation. miRNAs regulating HK2 and MAP7 were identified, including hsa-mir-484 (HK2) and hsa-mir-17-5p, hsa-mir-93-5p, hsa-mir-106b-5p, among others (MAP7). Discussion: EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line. Conclusion: More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.