Polygamain, a new microtubule depolymerizing agent that occupies a unique pharmacophore in the colchicine site.

ABSTRACT: Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant mitotic spindles that led to G(2)/M arrest. Polygamain has potent antiproliferative activities against a wide range of cancer cell lines, with an average IC(50) of 52.7 nM. Clonogenic studies indicate that polygamain effectively inhibits PC-3 colony formation and has excellent cellular persistence after washout. In addition, polygamain is able to circumvent two clinically relevant mechanisms of drug resistance, the expression of P-glycoprotein and the βIII isotype of tubulin.

SUBMITTER: Hartley RM 

PROVIDER: S-EPMC3286304 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature