Thiostrepton

An inhibitor of FoxM1

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Background

Thiazole antibiotic thiostrepton is an inhibitor of Forkhead box M1 (FOXM1), which effectively reduces cancer cell growth through downregulation of FOXM1. FOXM1 is a transcription factors that regulate expression of genes involved in maintenance of genomic stability and cell cycle progression.

In vitro: Thiostrepton inhibits the transcriptional activity and FOXM1 expression, and induces strong apoptosis in human cancer cells of different origin that correlates with suppression of FOXM1, including leukemia, neuroblastoma, liver cancer, melanoma and prostate cancer cells. Thiostrepton binds FOXM1 on the promoter site to inhibit transcriptional activity of FOXM1 through the FOXM1 autoregulation mechanism [1].

In vivo: Thiostrepton suppressed tumor growth in a human breast cancer xenograft model. Treatment with developed micelle-thiostrepton nanoparticles decreased xenograft tumor growth induced by the human MDA-MB-231 breast and HepG2 liver cancer cell lines. These apoptosis activities in drug-treated tumors were correlated with in vivo suppression of oncogenic FOXM1 [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Gartel AL.? Suppression of the Oncogenic Transcription Factor FOXM1 by Proteasome Inhibitors. Scientifica (Cairo). 2014;2014:596528.