title: Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment.
abstract: Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells.
authors: Faculty of Science, Universiti Tunku Abdul Rahman, Bandar Barat, Kampar, Perak, Malaysia.
authors: W H
authors: WH
authors: Yap
authors: K S
authors: KS
authors: Khoo
authors: S H
authors: SH
authors: Lim
authors: C C
authors: CC
authors: Yeo
authors: Y M
authors: YM
authors: Lim
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D031330:Coleus / Q000737:chemistry; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D011755:Pyrophosphatases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D050777:Stathmin / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D020543:Proteome; D011755:Pyrophosphatases; D050777:Stathmin; D014315:Triterpenes; C530104:CCND1 protein, human; C500985:MAPRE1 protein, human; C493995:STMN1 protein, human; C091775:ran-binding protein 1; C412811:maslinic acid; D009828:Oleanolic Acid; C020020:dUTP pyrophosphatase