Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity.

Obesity is biologically characterized at the cellular level by an increase in the number and size of adipocytes differentiated from fibroblastic pre-adipocytes in adipose tissue. In this study, we focused on the relationship between the influence of flavonoids on cell population growth and their antioxidant activity. The results showed that the inhibition of flavonoids (naringenin, rutin, hesperidin, resveratrol, naringin and quercetin) on 3T3-L1 pre-adipocytes was 28.3, 8.1, 11.1, 33.2, 5.6 and 71.5%, respectively. In oxygen radical absorbance capacity (ORAC) assay, quercetin had the highest ORAC(ROO) value among the six flavonoids tested. Apoptosis assays showed that quercetin increased apoptotic cells in time- and dose-dependent manner. Treatment of cells with quercetin decreased the mitochondrial membrane potential in the courses of time and dose. The cell apoptosis/necrosis assay showed that quercetin increased the number of apoptotic cells, but not necrotic cells. Quercetin treatment of cells caused a significant time- and dose-dependent increase in the caspase-3 activity. Western analysis indicated that treatment of quercetin markedly down-regulated PARP and Bcl-2 proteins, and activated caspase-3, Bax, and Bak proteins. These results indicate that quercetin efficiently inhibits cell population growth and induction of apoptosis in 3T3-L1 pre-adipocytes.