Cladosporols A and B, two natural peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibit adipogenesis in 3\u202fT3-L1 preadipocytes and cause a conditioned-culture-medium-dependent arrest of HT-29 cell proliferation.

Abstract

BACKGROUND\nObesity and type 2 diabetes mellitus, which are widespread throughout the world, require therapeutic interventions targeted to solve clinical problems (insulin resistance, hyperglycaemia, dyslipidaemia and steatosis). Several natural compounds are now part of the therapeutic repertoire developed to better manage these pathological conditions. Cladosporols, secondary metabolites from the fungus Cladosporium tenuissimum, have been characterised for their ability to control cell proliferation in human colon cancer cell lines through peroxisome proliferator-activated receptor gamma (PPARγ)-mediated modulation of gene expression. Here, we report data concerning the ability of cladosporols to regulate the differentiation of murine 3\u202fT3-L1 preadipocytes.\n\n\nMETHODS\nCell counting and MTT assay were used for analysing cell proliferation. RT-PCR and Western blotting assays were performed to evaluate differentiation marker expression. Cell migration was analysed by wound-healing assay.\n\n\nRESULTS\nWe showed that cladosporol A and B inhibited the storage of lipids in 3\u202fT3-L1 mature adipocytes, while their administration did not affect the proliferative ability of preadipocytes. Moreover, both cladosporols downregulated mRNA and protein levels of early (C/EBPα and PPARγ) and late (aP2, LPL, FASN, GLUT-4, adiponectin and leptin) differentiation markers of adipogenesis. Finally, we found that proliferation and migration of HT-29 colorectal cancer cells were inhibited by conditioned medium from cladosporol-treated 3\u202fT3-L1 cells compared with the preadipocyte conditioned medium.\n\n\nCONCLUSIONS\nTo our knowledge, this is the first report describing that cladosporols inhibit in vitro adipogenesis and through this inhibition may interfere with HT-29 cancer cell growth and migration.\n\n\nGENERAL SIGNIFICANCE\nCladosporols are promising tools to inhibit concomitantly adipogenesis and control colon cancer initiation and progression.