Modulators of epithelial-mesenchymal transitions in prostate cancer: potential for novel therapeutics development.

Research in the area of hallmarks of cancer has opened the possibility of designing novel therapeutic interventions based on modulating cancer properties. Interestingly, the epithelial-mesenchymal transition (EMT), important in both tumour growth and metastasis, has not been targeted in prostate cancer (PCa). Previously, in a repositioning screen, three new chemicals that modulate EMT in PCa (LLSO1 - NNC-55-0396 dihydrochloride; LLSO2 - Nemadipine A; LLSO3 - Naltrexone hydrochloride) have been found. This study aims to investigate how they work mechanistically as well as the effect of these LLSOs on the properties of PCa cells both in vitro and in vivo. Although these LLSOs exhibited varying effects on different cancer cell lines, all of them modulated EMT by inhibiting the migration of PCa cells. LLSO3 also exhibited a significant inhibitory effect on tumour growth in vivo, concomitant with an increase in the expression levels of E-cadherin. Further investigation was conducted to obtain mechanistic insights into the LLSO compounds mode of action. In conclusion, our work strongly supports that LLSO compounds may become important candidates for targeted therapeutics in prostate cancer.