Differential influence of Oroxylum indicum root and leaf metabolites on the proliferation and migration of breast cancer cells

• O. indicum root and leaf tissue show differential metabolomic profiles. • O. indicum root and leaf metabolites have differential apoptotic potential. • The root extracts inhibit the migration of breast cancer cells. Exploring the tissue-wise (leaf vs. root) therapeutic potential of medicinally important plants like Oroxylum indicum (L.) Kurz widens the scope to decipher newer treatment regimens for diseases like cancer. We attempted to gain insight in this mechanism of differential anti-cancer potential of leaf and root extracts of the tree O. indicum . LC-MS/MS analysis and cytotoxicity of the O. indicum leaf and root extracts was performed. In-solution proteomics of the extract-treated and control MCF-7 cancer cells deciphered several differential proteins. In vitro experiments like MTT assay, caspase activity assay, migration assay, and real- time quantitative PCR helped validate the findings. The O. indicum leaf and root extracts have a differential abundance of various bioactive flavonoids like apigenin and biochanin-A. Leaf and root extract treatment modulated >2200 MCF-7 proteins belonging to several gene-ontology classes prominently representing nucleic-acid binding and cytoskeletal proteins; proteins regulating diverse biological and metabolic processes like signal transduction, enzyme modulation, membrane trafficking, protein folding, etc. More than 200 uniquely expressed proteins like DDX10, Septin-2, etc. were detected in O. indicum leaf and root extract-treated cells. The root-extract treated cells followed a strong, concentration-dependent apoptotic modality as reflected by their caspase activity, along with a differential regulation of genes regulating cell proliferation and apoptosis. Migration of the O. indicum root extract-treated cells was significantly reduced, as compared to that of the leaf extract-treated cells, reflecting likewise in the respective gene expression profiles. Metabolites from O. indicum root extracts cause proteome level changes in MCF-7 cells that manifest into potent migrastatic and anticancer properties which can be tapped for greater phytotherapeutic advances.