Molecular mechanism of Forkhead box M1 inhibition by thiostrepton in breast cancer cells.

Molecular mechanism of Forkhead box M1 inhibition by thiostrepton in breast cancer cells. Oncol Rep. 2019 Jul 08;: Authors: Kongsema M, Wongkhieo S, Khongkow M, Lam EW, Boonnoy P, Vongsangnak W, Wong-Ekkabut J Abstract Breast cancer is the most common type of malignancies in women worldwide, and genotoxic chemotherapeutic drugs are effective by causing DNA damage in cancer cells. However, >90% of patients with metastatic cancer are resistant to chemotherapy. The Forkhead box M1 (FOXM1) transcription factor plays a pivotal role in the resistance of breast cancer cells to chemotherapy by promoting DNA damage repair following genotoxic drug treatment. The aim of the present study was to investigate the inhibition of the FOXM1 protein by thiostrepton, a natural antibiotic produced by the Streptomyces species. Experimental studies were designed to examine the effectiveness of thiostrepton in downregulating FOXM1 mRNA expression and activity, leading to senescence and apoptosis of breast cancer cells. The cytotoxicity of thiostrepton in breast cancer was determined using cell viability assay. Additionally, thiostrepton treatment decreased the mRNA expression of cyclin B1 (CCNB1), a downstream target of FOXM1. The present results indicated that thiostrepton inhibited FOXM1 mRNA expression and its effect on CCNB1. Molecular dynamic simulations were performed to study the interactions between FOXM1‑DNA and thiostrepton after molecular d...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research