Network pharmacology based investigation on the mechanism of tetrandrine against breast cancer

Tetrandrine, a bisbenzyl isoquinoline alkaloid from Stephania tetrandra was used in the present study. Roots of S. tetrandra is one of the major ingredients in herbal formulations of Traditional Chinese Medicine (TCM) viz. Fang Ji, Han-Dan-Gan-Le, Han-Dan-Gan-Le, Fang-Ji-Huang-Qi-Tang and Fang-Ji-Fu-Ling-Tang and, act as diuretic, antiinflammatory and antirheumatic agent. Alkaloids are the major components of S. tetrandra roots and tetrandrine is one of the important bisbenzyl isoquinoline alkaloids in this herb. In the present study, network pharmacology approach was used to identify major cancer signaling pathways and, protein molecules targeted by tetrandrine to induce an anticancer effect in breast cancer. Potential targets of tetrandrine against breast cancer were selected using already published articles and public databases and, were used in Protein-Protein Interaction (PPI) network analysis, Gene Ontology (GO), and Pathway enrichment analysis. PPI network analysis showed 65 nodes, 315 edges, and a clustering coefficient of 0.493. Tetrandrine targeted mainly on the proteins of mTOR, PI3-Akt, cell cycle and MAPK signaling pathways in addition to its action on cellular, biological and molecular functions as observed by Gene Ontology and KEGG analysis. Tetrandrine induces anticancer effect in breast cancer by targeting PI3K-Akt, mTOR and MAPK and cell cycle pathways.