Investigation of the biological mode of action of clerocidin using whole cell assays

Clerocidin, a diterpenoid natural product, has been shown in vitro to inhib it DNA religation following cleavage by topoisomerase II. Herein, we charac terize the efficacy and specificity of clerocidin in HeLa cells. Our result s suggest that clerocidin recognizes topoisomerase II as its main intracell ular target and binds to this enzyme prior to formation of the 'cleavable c omplex' with DNA. These pharmacological features attest to the promising ch emotherapeutic potential of this natural product. (C) 2001 Elsevier Science Ltd. All rights reserved.