MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer
- Front Oncol. 2020 Sep 29;10:571601. doi: 10.3389/fonc.2020.571601.
- 1. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
- 2. Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea.
- 3. Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea.
- 4. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
- 5. Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon, South Korea.
Although MASTL (microtubule-associated serine/threonine kinase-like) is an attractive target for Anticancer treatment, MASTL inhibitors with antitumor activity have not yet been reported. In this study, we have presented a novel MASTL Inhibitor, MKI-1, identified through in silico screening and in vitro analysis. Our data revealed that MKI-1 exerted antitumor and radiosensitizer activities in in vitro and in vivo models of breast Cancer. The mechanism of action of MKI-1 occurred through an increase in PP2A activity, which subsequently decreased the c-Myc protein content in breast Cancer cells. Moreover, the activity of MKI-1 in the regulation of MASTL-PP2A was validated in a mouse oocyte model. Our results have demonstrated a new small-molecule inhibitor of MASTL, MKI-1, which exerts antitumor and radiosensitizer activities through PP2A activation in breast Cancer in vitro and in vivo.