Wortmannin exhibits anticancer activity in oral cancer cell line by targeting PI3K, AKT and mTOR pathway | ||
| Avicenna Journal of Phytomedicine | ||
| دوره 16، شماره 2، خرداد و تیر 2026، صفحه 78-98 اصل مقاله (1.98 M) | ||
| نوع مقاله: Original Research Article | ||
| شناسه دیجیتال (DOI): 10.22038/ajp.2025.26226 | ||
| نویسندگان | ||
| GAURI M. KUMBHAR1؛ Poonam Suryawanshi2؛ VAIBHAV SUNIL LADKE* 3 | ||
| 1Department of Oral Pathology. Dr. D. Y. Patil Dental College and Hospital. Dr. D. Y. Patil Vidyapeeth, (Deemed to Be University). Sant Tukaram Nagar, Pimpri, Pune. India. | ||
| 2Central Research Facility. Dr. D. Y. Patil Medical College, Hospital and Research Centre. Dr. D. Y. Patil Vidyapeeth, (Deemed to Be University). Sant Tukaram Nagar, Pimpri, Pune. India. | ||
| 3Tissue Culture & Cell Biology Lab. Central Research Facility. Dr. D. Y. Patil Medical College, Hospital and Research Centre. Dr. D. Y. Patil Vidyapeeth, (Deemed to Be University). Sant Tukaram Nagar, Pimpri, Pune. India. 411018 | ||
| چکیده | ||
| Objective: Although the molecular mechanism by which wortmannin exerts its anticancer properties in solid tumors is not fully understood, particularly in the context of oral cancer where research is scarce, this study seeks to explore how wortmannin disrupts the PI3K pathway, consequently affecting the proliferation and apoptosis of human oral cancer cells. Materials and Methods: In-silico investigation included drug-likeness predictions, oral cancer and wortmannin targets, Protein-Protein Interactions (PPI), hub gene analysis, the top 10 KEGG pathways, Gene Ontology (GO), and molecular docking tests. In vitro experiments examined Viability Assay, apoptosis, cell cycle, Reactive Oxygen Species ROS and MMP levels, and gene expression. Results: Twenty commonly expressed genes affect cell proliferation, apoptosis, the PI3K signaling system, and the cell cycle as a result of in-silico analysis. Top 10 genes include mTOR, MAPK1, PIK3CA, PTGS2, MAPK8, AR, TERT, PIK3CB, PARP1, and PIK3CG. Wortmannin may treat oral cancer by targeting the PI3K/AKT signaling pathway, which is linked to these genes. In vitro tests showed anti-proliferative effects (IC50 = 3.6 ± 1 µM and IC25 = 1.8 ± 1 µM), late-stage apoptosis, reduced ROS, and MMP changes. Wortmannin downregulated mTOR, PIK3CA, ERK, PTEN, STAT3, and AKT. In addition, BCL2 and cMYC levels decreased and BAD and BAK expression increased. Conclusion: The in-silico strategy used in this study establishes the framework for cancer therapeutic research. This research has revealed wortmannin's ability to treat oral cancer in clinical settings. To validate in-silico and in-vitro findings, more assays and in-vivo research are needed. | ||
| کلیدواژهها | ||
| Oral cancer Wortmannin In؛ silico analysis PI3K/AKT Apoptosis Cell cycle | ||
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