Record Details

The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly dynamics through tubulin binding

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly dynamics through tubulin binding
 
Creator LOPUS, M
PANDA, D
 
Subject bimodal cell-death
nf-kappa-b
polymerization
mechanism
apoptosis
drugs
suppression
modulation
inhibitor
proteins
cancer chemotherapy
microtubules
mitosis
sanguinarine
tubulin
 
Description Sanguinarine has been shown to inhibit proliferation of several types of human cancer cell including multidrug-resistant cells, whereas it has minimal cytotoxicity against normal cells such as neutrophils and keratinocytes. By analyzing the antiproliferative activity of sanguinarine in relation to its effects on mitosis and microtubule assembly, we found that it inhibits cancer cell proliferation by a novel mechanism. It inhibited HeLa cell proliferation with a half-maximal inhibitory concentration of 1.6 +/- 0.1 mu M. In its lower effective inhibitory concentration range, sanguinarine depolymerized microtubules of both interphase and mitotic cells and perturbed chromosome organization in mitotic HeLa cells. At concentrations of 2 mu M, it induced bundling of interphase microtubules and formation of granular tubulin aggregates. A brief exposure of HeLa cells to sanguinarine caused irreversible depolymerization of the microtubules, inhibited cell proliferation, and induced cell death. However, in contrast with several other microtubule-depolymerizing agents, sanguinarine did not arrest cell cycle progression at mitosis. In vitro, low concentrations of sanguinarine inhibited microtubule assembly. At higher concentrations (> 40 mu M), it altered polymer morphology. Further, it induced aggregation of tubulin in the presence of microtubule-associated proteins. The binding of sanguinarine to tubulin induces conformational changes in tubulin. Together, the results suggest that sanguinarine inhibits cell proliferation at least in part by perturbing microtubule assembly dynamics.
 
Publisher BLACKWELL PUBLISHING
 
Date 2011-07-19T04:52:19Z
2011-12-26T12:51:00Z
2011-12-27T05:37:18Z
2011-07-19T04:52:19Z
2011-12-26T12:51:00Z
2011-12-27T05:37:18Z
2006
 
Type Article
 
Identifier FEBS JOURNAL, 273(10), 2139-2150
1742-464X
http://dx.doi.org/10.1111/j.1742-4658.2006.05227.x
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5179
http://hdl.handle.net/10054/5179
 
Language en