Proteomic analysis of Caco-2 cells treated with monacolin K.
Monascus species is an important traditional fermentation fungus used on food. Monacolin K (a secondary metabolite of Monascus, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase) in inhibition of mevalonate synthesis may result in reductions of isoprenoid prenylation in cells. Impairment of protein isoprenoid prenylation has been related to anticancer effect in cancer cells. As a functional food for Monascus, however, the molecular mechanisms responsible for the anti-proliferate effect of monacolin K in cancer cells are not clear. We used proteomic analysis by two-dimensional gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS), tandem mass spectrometry (MS/MS), and database interrogation to separate and identify the proteins of Caco-2 cells treated with monacolin K. The results showed that monacolin K inhibited the proliferation of Caco-2 cells in a dose-dependent manner. The identified proteins in proteomic analysis included anti-oxidation enzymes related to reactive oxygen species stress, cytoskeleton proteins, glycolytic enzymes, and enzymes involved in mediating protein interactions. Furthermore, glutathione S-transferase P 1 and cytoskeleton-8, -18, and -19 revealed a down-regulation in a dose-dependent manner in exposure of Caco-2 cells to monacolin K.
Lin
Wun-Yuan
WY
Department of Food Science, Nutrition and Nutraceutical Biotechnology, Shih Chien University, Taipei, Taiwan, Republic of China.
Song
Ching-Yung
CY
Pan
Tzu-Ming
TM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D017368:Protein Prenylation / Q000187:drug effects; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D008148:Lovastatin