Evaluation of the combinatorial effect ofandon human breast cancer cells.
3 Biotech. 2019 Nov ;9(11):428. Epub 2019 Oct 29. PMID: 31696033
The present study was aimed to investigate the anticancer potential of the combination treatment of(TC) and(ZO) using network pharmacology approach. In silico analysis of the anticancer activity of TC + ZO was carried out using Cytoscape 3.2.0 software to elucidate the mechanism. The MTT assay confirms the combination of TC and ZO is more active (IC; 2 μg ml) as compared to TC (509 μg ml) and ZO (1 mg ml) alone in MCF-7 cells. The TC + ZO combination treatment inhibits DNA synthesis, migration, and induces apoptosis in MCF-7 cells as compared to TC and ZO alone at a concentration of 1 µg ml. TC + ZO combination treatment arrested cell cycle significantly at the G/Gphase. The proposed synergistic activity of the two herbs in the treatment of several cancers was correlated with an appropriate associated target/s, based on the pharmacological network. Interestingly, when both the plants used in combination, were found to regulate a total of 16 genes in 27 types of cancers. Further, ALOX5, MMP2, and MMP9 genes were identified as major targets which are responsible for the TC + ZO anticancer activity. According to merged and sub-networks of source-bioactive, bioactive-target, target-disease of TC, ZO alone and their combination; MMP9 was selected for validation purpose. The real-time PCR analysis confirmed that the TC + ZO combination treatment significantly down-regulated MMP9 mRNA expression by fivefold via up-regulation of its downstream target ER-α by 3.5-fold. In conclusion, the network analysis and in vitro validation confirmed the potent synergistic activity of TC + ZO combination treatment in breast cancer.