MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer
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 v...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.571601/full |
| _version_ | 1818285720456921088 |
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| author | Ah-Young Kim Yi Na Yoon Yi Na Yoon Jiyeon Leem Jee-Young Lee Kwan-Young Jung Minsung Kang Jiyeon Ahn Sang-Gu Hwang Jeong Su Oh Jae-Sung Kim Jae-Sung Kim |
| author_facet | Ah-Young Kim Yi Na Yoon Yi Na Yoon Jiyeon Leem Jee-Young Lee Kwan-Young Jung Minsung Kang Jiyeon Ahn Sang-Gu Hwang Jeong Su Oh Jae-Sung Kim Jae-Sung Kim |
| author_sort | Ah-Young Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T01:13:11Z |
| format | Article |
| id | doaj.art-deebaccfdb9545038d2e114446e25c67 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-13T01:13:11Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-deebaccfdb9545038d2e114446e25c672022-12-22T00:04:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.571601571601MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast CancerAh-Young Kim0Yi Na Yoon1Yi Na Yoon2Jiyeon Leem3Jee-Young Lee4Kwan-Young Jung5Minsung Kang6Jiyeon Ahn7Sang-Gu Hwang8Jeong Su Oh9Jae-Sung Kim10Jae-Sung Kim11Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaRadiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, South KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South KoreaCenter for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon, South KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, South KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South KoreaRadiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South KoreaAlthough 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.https://www.frontiersin.org/article/10.3389/fonc.2020.571601/fullMASTLPP2Aantitumorbreast cancerradiosensitizer |
| spellingShingle | Ah-Young Kim Yi Na Yoon Yi Na Yoon Jiyeon Leem Jee-Young Lee Kwan-Young Jung Minsung Kang Jiyeon Ahn Sang-Gu Hwang Jeong Su Oh Jae-Sung Kim Jae-Sung Kim MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer Frontiers in Oncology MASTL PP2A antitumor breast cancer radiosensitizer |
| title | MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer |
| title_full | MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer |
| title_fullStr | MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer |
| title_full_unstemmed | MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer |
| title_short | MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer |
| title_sort | mki 1 a novel small molecule inhibitor of mastl exerts antitumor and radiosensitizer activities through pp2a activation in breast cancer |
| topic | MASTL PP2A antitumor breast cancer radiosensitizer |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.571601/full |
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