Bioinformatics and molecular docking analysis to identify therapeutic targets of andrographolide in cervical squamous cell carcinoma

Abstract

Background: Cervical cancer is Indonesia’s second leading cause of cancer, predominantly squamous cell carcinoma. Andrographolide, a natural anticancer compound from Andrographis paniculata, can be evaluated in silico for its therapeutic target in this cancer.

Objective: To identify andrographolide’s therapeutic target in squamous cell carcinoma of the cervix.

Methods: Bioinformatics analysis intersected genes dysregulated in cancer with genes regulated by andrographolide. Potential therapeutic target genes were analyzed for cancer relevance, and the most probable targets were docked with andrographolide.

Results: Eighty-three potential therapeutic target genes were identified; gene ontology and KEGG pathway analysis confirmed their cancer relevance. Three targets, MAPK3, MMP9, and JAK2, were selected for docking. Binding energies (kcal/mol) between andrographolide and MAPK3, MMP9, and JAK2 were -9.954, -9.470, and -8.482, respectively, comparable to their positive controls (-10.050, -9.459, and -9.422). Andrographolide interacted with key residues including Ile48/Tyr53 (MAPK3), His230/His236/Pro246/Met247 (MMP9), and Leu983 (JAK2).

Conclusion: MAPK3, MMP9, and JAK2 are potential therapeutic targets for andrographolide in treating squamous cell carcinoma of the cervix.