METABOLOMIC AND PROTEOMIC CHARACTERIZATION OF INDIGENOUS MEDICINAL PLANTS FOR TARGETED ANTICANCER DRUG DISCOVERY IN PAKISTAN

Abstract

Cancer remains a major global health burden characterized by genetic heterogeneity, therapeutic resistance, and dysregulation of multiple signaling pathways. Conventional anticancer therapies are often limited by toxicity, high cost, and lack of specificity, particularly in low- and middle-income countries. In this context, indigenous medicinal plants of Pakistan represent a promising yet underexplored source of bioactive compounds with potential anticancer properties. This study aimed to systematically characterize the metabolomic and proteomic profiles of selected medicinal plants and to identify multi-target anticancer mechanisms through integrated systems biology and network pharmacology approaches. A multi-omics analytical framework was employed, utilizing LC–MS/MS and GC–MS for metabolomic profiling and shotgun proteomics for protein identification and functional annotation. Bioinformatics tools were applied for data processing, differential analysis, and pathway enrichment. Identified metabolites and proteins were mapped onto cancer-related signaling networks, including PI3K/Akt, MAPK, p53, and NF-κB pathways. Network pharmacology analysis was conducted to construct compound–target–pathway interaction maps and to elucidate synergistic mechanisms of action. The integrated analysis revealed that selected medicinal plants possess diverse secondary metabolites, including flavonoids, alkaloids, terpenoids, and phenolic compounds, along with functionally active proteins associated with apoptosis, stress response, and detoxification processes. Pathway enrichment analysis demonstrated significant modulation of key oncogenic signaling cascades involved in cell proliferation, survival, and apoptosis regulation. The findings suggest that these plants exert anticancer effects through a multi-target, systems-level mechanism rather than single-compound activity. This study provides a comprehensive omics-based framework for anticancer drug discovery from indigenous medicinal plants of Pakistan and bridges the gap between ethnopharmacological knowledge and modern computational biology. The results offer a scientific basis for further experimental validation and potential development of novel, cost-effective anticancer therapeutics.