Leucodine blocks mitotic clonal expansion during preadipoctye differentiation through cell cycle arrest

In this study, we investigated the effect of 11,13 dihydro-[11R]-dehydroleucodine (i.e., leucodine), a sesquiterpene lactone obtained from the reduction of dehydroleucodine, on adipogenesis of 3T3-L1 preadipocyte. 11,13 dihydro-[11R]-dehydroleucodine blocked the accumulation of lipid droplets stained with Oil Red O and inhibited the increase of triglycerides in the adipocytes (IC50: 71.0 ± 4.1 μM). Expressions of Glut-4, adiponectin and perilipin-2 were blocked in the presence of 11,13 dihydro-[11R]-dehydroleucodine. Furthermore, expression of PPARγ and C/EBPα was significantly inhibited by 11,13 dihydro-[11R]-dehydroleucodine as well as the expression of C/EBPβ was also strongly inhibited in time- and concentration-dependent manner. This is consistent with the inhibitory effect of 11,13 dihydro-[11R]-dehydroleucodine on the early stage of adipogenesis. Thus, the proliferation of preadipocytes were also suppressed by addition of 11,13 dihydro-[11R]-dehydroleucodine during the first 48 h after induction. These results indicate that 11,13 dihydro-[11R]-dehydroleucodine may selectively affect mitotic clonal expansion to block preadipocyte differentiation. 11,13 dihydro-[11R]-dehydroleucodine stopped the cell cycle at the G0/G1 phase by diminishing the increase of phosphorylation of Rb, Erk1/2 and Akt while increasing the expression of p27. Collectively, our results indicate that the inhibition of early stage preadipocytes differentiation by 11,13 dihydro-[11R]-dehyd...
Source: Phytochemistry Letters - Category: Chemistry Source Type: research