TY - JOUR T1 - Obtusilactone B from <em>Machilus thunbergii</em> Targets Barrier-to-autointegration Factor to Treat Cancer JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.082578 SP - mol.112.082578 AU - Wanil Kim AU - Ha-Na Lyu AU - Hyun-Sook Kwon AU - Ye Seul Kim AU - Kyung-Ha Lee AU - Do-Yeon Kim AU - Goutam Chakraborty AU - Kwan Yong Choi AU - Ho Sup Yoon AU - Kyong-Tai Kim Y1 - 2012/11/13 UR - http://molpharm.aspetjournals.org/content/early/2012/11/13/mol.112.082578.abstract N2 - 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 employ 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. Here, 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 anti-cancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment. ER -