KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1
KRIBB11, an HSF1 inhibitor, was shown to sensitize various types of cancer cells to treatment with several anticancer drugs. However, the exclusive effects of KRIBB11 in preventing the growth of glioblastoma cells and the related mechanisms have not been elucidated yet. Herein, we aimed to examine t...
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MDPI AG
2021-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/14/4165 |
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| author | Kyunghyun Yoo Hye-Hyeon Yun Soon-Young Jung Jeong-Hwa Lee |
| author_facet | Kyunghyun Yoo Hye-Hyeon Yun Soon-Young Jung Jeong-Hwa Lee |
| author_sort | Kyunghyun Yoo |
| collection | DOAJ |
| description | KRIBB11, an HSF1 inhibitor, was shown to sensitize various types of cancer cells to treatment with several anticancer drugs. However, the exclusive effects of KRIBB11 in preventing the growth of glioblastoma cells and the related mechanisms have not been elucidated yet. Herein, we aimed to examine the potential of KRIBB11 as an anticancer agent for glioblastoma. Using MTT and colony formation assays and Western blotting for c-PARP, we demonstrated that KRIBB11 substantially inhibits the growth of A172 glioma cells by inducing apoptosis. At the molecular level, KRIBB11 decreased anti-apoptotic protein MCL-1 levels, which was attributable to the increase in MULE ubiquitin ligase levels. However, the constitutive activity of HSF1 in A172 cells was not influenced by the exclusive treatment with KRIBB11. Additionally, based on cycloheximide chase assay, we found that KRIBB11 markedly retarded the degradation of MULE. In conclusion, stabilization of MULE upon KRIBB11 treatment is apparently an essential step for degradation of MCL-1 and the subsequent induction of apoptosis in A172 cells. Our results have expanded the knowledge on molecular pathways controlled by KRIBB11 and could be potentially effective for developing an inhibitory therapeutic strategy for glioblastoma. |
| first_indexed | 2024-03-10T09:30:51Z |
| format | Article |
| id | doaj.art-c4a817accc7946d4a4c2435b99a78612 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:30:51Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-c4a817accc7946d4a4c2435b99a786122023-11-22T04:29:29ZengMDPI AGMolecules1420-30492021-07-012614416510.3390/molecules26144165KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1Kyunghyun Yoo0Hye-Hyeon Yun1Soon-Young Jung2Jeong-Hwa Lee3Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 16591, KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 16591, KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 16591, KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 16591, KoreaKRIBB11, an HSF1 inhibitor, was shown to sensitize various types of cancer cells to treatment with several anticancer drugs. However, the exclusive effects of KRIBB11 in preventing the growth of glioblastoma cells and the related mechanisms have not been elucidated yet. Herein, we aimed to examine the potential of KRIBB11 as an anticancer agent for glioblastoma. Using MTT and colony formation assays and Western blotting for c-PARP, we demonstrated that KRIBB11 substantially inhibits the growth of A172 glioma cells by inducing apoptosis. At the molecular level, KRIBB11 decreased anti-apoptotic protein MCL-1 levels, which was attributable to the increase in MULE ubiquitin ligase levels. However, the constitutive activity of HSF1 in A172 cells was not influenced by the exclusive treatment with KRIBB11. Additionally, based on cycloheximide chase assay, we found that KRIBB11 markedly retarded the degradation of MULE. In conclusion, stabilization of MULE upon KRIBB11 treatment is apparently an essential step for degradation of MCL-1 and the subsequent induction of apoptosis in A172 cells. Our results have expanded the knowledge on molecular pathways controlled by KRIBB11 and could be potentially effective for developing an inhibitory therapeutic strategy for glioblastoma.https://www.mdpi.com/1420-3049/26/14/4165glioblastomaKRIBB11MCL-1apoptosis |
| spellingShingle | Kyunghyun Yoo Hye-Hyeon Yun Soon-Young Jung Jeong-Hwa Lee KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 Molecules glioblastoma KRIBB11 MCL-1 apoptosis |
| title | KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 |
| title_full | KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 |
| title_fullStr | KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 |
| title_full_unstemmed | KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 |
| title_short | KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1 |
| title_sort | kribb11 induces apoptosis in a172 glioblastoma cells via mule dependent degradation of mcl 1 |
| topic | glioblastoma KRIBB11 MCL-1 apoptosis |
| url | https://www.mdpi.com/1420-3049/26/14/4165 |
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