Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer
Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecu...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Online Access: | https://hdl.handle.net/10356/102247 http://hdl.handle.net/10220/19055 |
| _version_ | 1811693910211166208 |
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| author | Kim, Wanil Lyu, Ha-Na Kwon, Hyun-Sook Kim, Ye Seul Lee, Kyung-Ha Kim, Do-Yeon Chakraborty, Goutam Choi, Kwan Yong Yoon, Ho Sup Kim, Kyong-Tai |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Kim, Wanil Lyu, Ha-Na Kwon, Hyun-Sook Kim, Ye Seul Lee, Kyung-Ha Kim, Do-Yeon Chakraborty, Goutam Choi, Kwan Yong Yoon, Ho Sup Kim, Kyong-Tai |
| author_sort | Kim, Wanil |
| collection | NTU |
| description | Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer. Obtusilactone B is a butanolide derivative purified from Machilus thunbergii. In this study, we show that obtusilactone B functions as a small-molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)–mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is important in maintaining lamin integrity, which is closely associated with diseases that include cancer. Specific binding of obtusilactone B to BAF suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment. |
| first_indexed | 2024-10-01T06:59:11Z |
| format | Journal Article |
| id | ntu-10356/102247 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:59:11Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1022472020-03-07T12:18:16Z Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer Kim, Wanil Lyu, Ha-Na Kwon, Hyun-Sook Kim, Ye Seul Lee, Kyung-Ha Kim, Do-Yeon Chakraborty, Goutam Choi, Kwan Yong Yoon, Ho Sup Kim, Kyong-Tai School of Biological Sciences Biological Sciences Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer. Obtusilactone B is a butanolide derivative purified from Machilus thunbergii. In this study, we show that obtusilactone B functions as a small-molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)–mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is important in maintaining lamin integrity, which is closely associated with diseases that include cancer. Specific binding of obtusilactone B to BAF suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment. 2014-03-31T08:54:26Z 2019-12-06T20:52:11Z 2014-03-31T08:54:26Z 2019-12-06T20:52:11Z 2013 2013 Journal Article Kim, W., Lyu, H.-N., Kwon, H.-S., Kim, Y. S., Lee, K.-H., Kim, D.-Y., et al. (2013). Obtusilactone B from Machilus Thunbergii Targets Barrier-to-Autointegration Factor to Treat Cancer. Molecular Pharmacology, 83(2), 367-376. 1521-0111 https://hdl.handle.net/10356/102247 http://hdl.handle.net/10220/19055 10.1124/mol.112.082578 en Molecular pharmacology © 2013 The American Society for Pharmacology and Experimental Therapeutics. |
| spellingShingle | Biological Sciences Kim, Wanil Lyu, Ha-Na Kwon, Hyun-Sook Kim, Ye Seul Lee, Kyung-Ha Kim, Do-Yeon Chakraborty, Goutam Choi, Kwan Yong Yoon, Ho Sup Kim, Kyong-Tai Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title_full | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title_fullStr | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title_full_unstemmed | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title_short | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer |
| title_sort | obtusilactone b from machilus thunbergii targets barrier to autointegration factor to treat cancer |
| topic | Biological Sciences |
| url | https://hdl.handle.net/10356/102247 http://hdl.handle.net/10220/19055 |
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