Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1

• DOI: 10.1371/journal.pbio.2000784
• Publication Date: 2017-06-01T13:37:25Z
• Authors: Manisha Juneja; Dennis Kobelt; Wolfgang Walther; Cynthia Voss; Janice Smith; Edgar Specker; Martin Neuenschwa...; Björn-Oliver Gohlke; Mathias Dahlmann; Silke Radetzki; Robert Preissner; Jens Peter von Kries; Peter Michael Schlag; Ulrike Stein
• Keywords: Rottlerin; Lovastatin

MACC1 (Metastasis Associated in Colon Cancer 1) is a key driver and prognostic biomarker for cancer progression metastasis large variety of solid tumor types, particularly colorectal (CRC). However, no inhibitors have been identified yet. Therefore, we aimed to target expression using luciferase reporter-based high-throughput screening with the ChemBioNet library more than 30,000 compounds. The small molecules lovastatin rottlerin emerged as most potent transcriptional inhibitors. They remarkably inhibited promoter activity expression, resulting reduced cell motility. Lovastatin impaired binding transcription factors c-Jun Sp1 promoter, thereby inhibiting transcription. Most importantly, CRC-xenografted mice, restricted liver metastasis. This is—to best our knowledge—the first identification restricting via novel MACC1. drug repositioning might be therapeutic value CRC patients.