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.