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https://hdl.handle.net/10356/102247
Title: | Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer | Authors: | 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 |
Keywords: | Biological Sciences | Issue Date: | 2013 | Source: | 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. | Series/Report no.: | Molecular pharmacology | Abstract: | 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. | URI: | https://hdl.handle.net/10356/102247 http://hdl.handle.net/10220/19055 |
ISSN: | 1521-0111 | DOI: | 10.1124/mol.112.082578 | Schools: | School of Biological Sciences | Rights: | © 2013 The American Society for Pharmacology and Experimental Therapeutics. | Fulltext Permission: | none | Fulltext Availability: | No Fulltext |
Appears in Collections: | SBS Journal Articles |
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