Transcriptome profiling of curcumin-treated T47D human breast cancer cells by a system-based approach

A systemic approach provides a comprehensive scheme from the molecular regulatory mechanism of drugs in living systems. This study investigated the regulatory mechanism of curcumin in breast cancer cells by analyzing the transcriptome alterations in T47D breast cancer cells. For this purpose, the cytotoxic effect of curcumin was evaluated by MTT assay after treating T47D cells with 0-50 mu M concentration of curcumin. Furthermore, transcriptome analysis was performed using RNA sequencing to find differentially expressed genes following curcumin treatment in T47D cells. Transcription factor and microRNA profiles related to curcumin gene signature were retrieved from related databases. A system-based network analysis was performed to deepen our understanding of the curcumin mechanism of action in T47D cells. In an independent analysis, a publicly available microarray dataset including gene expression and clinical data was used to evaluate the prognostic power of curcumin signature and its relation with patients' outcomes by the Cox model. Our results suggest that curcumin triggers cell death-related pathways and regulates the metabolism of lipids and apoptotic processes in T47D cells. Curcumin signature had significant prognostic power. Regulatory network analyses found specific proteins, microRNAs and transcription factors as the hub nodes, which corresponded to the effects of curcumin treatment. This work provides a picture of the cytotoxicity mechanism of curcumin and potential therapeutic targets for treatment optimization of breast cancer.