A research team led by Wolfgang Link and composed by other CBMR researchers, namely Bibiana Ferreira and Susana Machado, recently published a research article in PLOS ONE, the world’s first multidisciplinary open access journal in the field of science and medicine. The article results from the development of an innovative research in the field of cancer and suggests that LOM612 – a small chemical compound – can be used as a potent FOXO relocator.
The family of FOXO transcription factors is commonly inactivated in human tumours by posttranslational modifications and genetic variation within the FOXO3a gene is consistently associated with human longevity. This scenario represents an attractive therapeutic approach to treat cancer and age-related diseases by pharmacologically activation of FOXO proteins.
In order to identify agents capable of activating FOXOs, Wolfgang Link and his team tested a collection of small chemical compounds using image-based high content screening technology. The authors were able to show that LOM612 induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. According to the team, this activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. More importantly, LOM612 shows a potent antiproliferative effect in human cancer cell lines.