Role of the de novo Ceramide and Arachidonic Acid in Paclitaxel-Induced Apoptosis

  • Chin, Mi-Reyoung (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Kang, Mi-Sun (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Kim, Dae-Kyong (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University)
  • Published : 2003.10.01

Abstract

Recently, several reports suggest that ceramide formation has been implicated in the apoptosis signaling in response to chemotherapeutic agents. In this study, to enhance paclitaxel-mediated cytotoxicity and endogenous ceramide levels, we blocked ceramide metabolism using an inhibitor of glucosylceramide synthase, l-phenyl-2- dacanoylamino-3-morpholino-l-propanol(PDMP) and SM synthase, D609. Exposure of human breast cancer cells to paclitaxel accumulated de novo ceramide synthesis by enhancement of SPT activity 1.2-fold, whereas ceramide synthase activity was not altered. (omitted)

Keywords