Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters.

ABSTRACT:

Background

Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology.

Method and findings

A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak

SUBMITTER: Fayad W 

PROVIDER: S-EPMC2749935 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature