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Dynamic proteomic overview of glioblastoma cells (A172) exposed to perillyl alcohol
Authors:Juliana de Saldanha da Gama Fischer  Lujian Liao  Paulo C. Carvalho  Valmir C. Barbosa  Gilberto B. Domont  Maria da Gloria da Costa Carvalho  John R. Yates
Affiliation:1. Laboratory for Protein Chemistry, Chemistry Institute, and the Rio de Janeiro Proteomic Network, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA;3. Systems Engineering and Computer Science Program, COPPE, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;4. Laboratory for Control of Gene Expression, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Brazil
Abstract:Perillyl alcohol (POH) is a naturally occurring terpene and a promising chemotherapeutic agent for glioblastoma multiform; yet, little is known about its molecular effects. Here we present results of a semi-quantitative proteomic analysis of A172 cells exposed to POH for different time-periods (1′, 10′, 30′, 60′, 4 h, and 24 h). The analysis identified more than 4000 proteins; which were clustered using PatternLab for proteomics and then linked to Ras signaling, tissue homeostasis, induction of apoptosis, metallopeptidase activity, and ubiquitin-protein ligase activity. Our results make available one of the most complete protein repositories for the A172. Moreover, we detected the phosphorylation of GSK3β (Glycogen synthase kinase) and the inhibition of ERK's (extracellular signal regulated kinase) phosphorylation after 10′, which suggests a new mechanism of POH's activation for apoptosis.
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