Chemotranscriptomic analysis of 7-hydroxymatairesinol-related effects on MCF7 human breast tumor cells

Abstract

Introduction . Establishing the effects of anticancer drugs on the transcriptome is an important procedure in postgenomic pharmacology necessary to comprehensively assess the desired and undesirable effects of candidate drugs. Aim: to assess the effects of lignan 7-hydroxymatairesinol (7HMR) on breast tumor cells. Materials and Methods . Chemotranscriptome profiling was carried out in MCF7 cells (breast cancer cell line) after 24-hour incubation with 7HMR. The GEO (Gene Expression Omnibus) database contains samples of data from transcriptomic studies allowing to model dose-dependent compound-related effects on gene expression based on the chemograph-derived combinatorial analysis algorithms. As a result, a panel of genes with altered expression is generated, which are analyzed by the functional linkage method using the international nomenclature of Gene Ontology (GO) linked to biological roles of genes/proteins. Results . Dose-dependent effects of 7HMR on gene transcription (change in transcription by 5 % or more per 1 μmol 7HMR) were established for 3,468 out of 12,700 genes studied. 7HMR significantly reduced the expression of genes involved in maintaining cell proliferation (401 genes including those involved in telomere maintenance), protein synthesis (194 genes) and proteasomal protein degradation (70 genes), energy metabolism in tumor cells (91 genes) and chronic inflammation (148 genes). A decline in the expression of such gene groups retards the processes of proliferation and vital activity along with protecting host body from excessive inflammation. 7HMR contributed to a predominant increase in the transcription of gene groups involved in antitumor activity (more than 100 genes), including the genes involved in maintaining antitumor immunity as well as those mediating the antitumor effects of vitamin D, retinoids, and vitamin C. Conclusion . The revealed changes in gene transcription enhance 7HMR-related effects on proteome proteins and suggest the prospects for using 7HMR for effective and safe prevention and treatment of nodular mastopathy and breast cancer.