PT  - JOURNAL ARTICLE
AU  - Kim, Wanil
AU  - Lyu, Ha-Na
AU  - Kwon, Hyun-Sook
AU  - Kim, Ye Seul
AU  - Lee, Kyung-Ha
AU  - Kim, Do-Yeon
AU  - Chakraborty, Goutam
AU  - Choi, Kwan Yong
AU  - Yoon, Ho Sup
AU  - Kim, Kyong-Tai
TI  - Obtusilactone B from <em>Machilus Thunbergii</em> Targets Barrier-to-Autointegration Factor to Treat Cancer
AID  - 10.1124/mol.112.082578
DP  - 2013 Feb 01
TA  - Molecular Pharmacology
PG  - 367--376
VI  - 83
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/83/2/367.short
4100  - http://molpharm.aspetjournals.org/content/83/2/367.full
SO  - Mol Pharmacol2013 Feb 01; 83
AB  - 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.