Effects of 13-acetoxyrolandrolide on colon cancer cells

U Muñoz Acuña; S Matthew; J Wittwer; L Pan; AD Kinghorn; EJ Carcache de Blanco

doi:10.1055/s-0032-1321004

Planta Medica, Table of Contents

Effects of 13-acetoxyrolandrolide on colon cancer cells

U Muñoz Acuña ¹, S Matthew ¹, J Wittwer ¹, L Pan ², AD Kinghorn ², EJ Carcache de Blanco ²

¹Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Lloyd M. Parks Hall 500 W. 12th Avenue, Columbus, OH 43210
²Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Lloyd M. Parks Hall 500 W. 12th Avenue, Columbus, OH 43210

Abstract

The compound 13-acetoxyrolandrolide was previously isolated from Rolandra fruticosa (L.) Kuntze (Asteraceae). Potent cytotoxic activity was found against HT-29 colon cancer cells compared with paclitaxel, EC₅₀=0.16µM and EC₅₀=0.0006µM, respectively. Initial screening showed that the NF-κB inhibition was IC₅₀=7.1µM. The mechanism of action through which transcription factor NF-κB was further investigated and the expression of up-stream mediators such as IKKα and IKKβ was analyzed by immunoblotting. In this study, 13-acetoxyrolandrolide demonstrated similar effects to staurosporine, inducing loss of the mitochondrial membrane potential (ΨΔm). Cell cycle analysis showed a significant increase of HT-29 cells in the G₁-phase after treatment, and 68% of treated cells were found in this G₁-phase compared to 55% in the untreated cells. In addition, high intracellular levels of ROS were also detected in treated cells. These findings suggest that the mitochondrial activity of cancer cells was affected and NF-κB was inhibited, possibly through an oxidative pathway. Thus, chemical optimization of 13-acetoxyrolandrolide might lead to the discovery of a new potential cancer chemotherapeutic agent for the treatment of colon cancer.