Arnatchai Maiuthed1,2, Tatchakorn Pinkhien2, Supakarn Chamni3, Khanit Suwanborirux3, Naoki Saito4, Nareerat Petpiroon2, Pithi Chanvorachote5,2. 1. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. 2. Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand. 3. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. 4. Department of Pharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, Tokyo, Japan. 5. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand pithi.c@chula.ac.th pithi_chan@yahoo.com.
Abstract
BACKGROUND: A newly-synthesized derivative of renieramycin M (RM), an anticancer lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O-cinnamoyl ester (CIN-RM), was investigated here for its activity against non-small cell lung cancer cells. MATERIALS AND METHODS: Cytotoxicity effects of CIN-RM and RM on H292 lung cancer cells were determined by the MTT assay. We also investigated the mechanism of CIN-RM-mediated apoptosis and mechanism of action of this compound by western blotting. RESULTS: CIN-RM showed more potent cytotoxicity than its parental compound (RM) against H292 lung cancer cells. At concentrations of 15-60 μM, CIN-RM significantly induced apoptosis by increasing expression of apoptosis-inducing factor (AIF) and activation of caspase-3 and -9. For up-stream mechanism, CIN-RM mediated apoptosis through a p53-dependent mechanism, that consequently down-regulated anti-apoptotic B-cell lymphoma 2 (BCL2), while increasing the level of pro-apoptotic BCL2-associated X (BAX). In addition, phosphorylation of pro-survival protein AKT was found to be dramatically reduced. CONCLUSION: This study revealed the potential of CIN-RM for apoptosis induction and in the development of a novel anticancer agent. Copyright
BACKGROUND: A newly-synthesized derivative of renieramycin M (RM), an anticancer lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O-cinnamoyl ester (CIN-RM), was investigated here for its activity against non-small cell lung cancer cells. MATERIALS AND METHODS:Cytotoxicity effects of CIN-RM and RM on H292 lung cancer cells were determined by the MTT assay. We also investigated the mechanism of CIN-RM-mediated apoptosis and mechanism of action of this compound by western blotting. RESULTS:CIN-RM showed more potent cytotoxicity than its parental compound (RM) against H292 lung cancer cells. At concentrations of 15-60 μM, CIN-RM significantly induced apoptosis by increasing expression of apoptosis-inducing factor (AIF) and activation of caspase-3 and -9. For up-stream mechanism, CIN-RM mediated apoptosis through a p53-dependent mechanism, that consequently down-regulated anti-apoptotic B-cell lymphoma 2 (BCL2), while increasing the level of pro-apoptotic BCL2-associated X (BAX). In addition, phosphorylation of pro-survival protein AKT was found to be dramatically reduced. CONCLUSION: This study revealed the potential of CIN-RM for apoptosis induction and in the development of a novel anticancer agent. Copyright