Please use this identifier to cite or link to this item: 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
Rights: © 2013 The American Society for Pharmacology and Experimental Therapeutics.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.