Fatostatin ia an inhibitor of sterol regulatory element binding protein (SREBP). It impairs the activation of SREBP-1 and SREBP-2.
Fatostatin inhibits the insulin-induced adipogenesis of 3T3-L1 cells and the serum-independent growth of human androgen-independent prostate cancer (DU145) cells. Fatostatin suppresses cell proliferation and anchorage-independent colony formation in both androgen-responsive LNCaP and androgen-insensitive C4-2B prostate cancer cells. Fatostatin blocks the activation of SREBPs in cells in tissue culture.Fatostatin also reduced in vitro invasion and migration in both cell lines. Further, fatostatin causes G2/M cell cycle arrest and induces apoptosis by increasing caspase-3/7 activity and the cleavages of caspase-3 and PARP.
Fatostatin significantly inhibits subcutaneous C4-2B tumor growth and markedly decreases serum PSA level compared to the control group. Fatostatin blocks increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake.
Cell lines: CHO-K1 cells. Concentrations: 20 μM. Incubation Time: 20 h. Method: On day 0,CHO-K1 cells are plated out onto a 96-well plate in medium A.On day 2,the cells are transiently cotransfected with pCMV-PLAP-BP2(513–1141),pCMV-SCAP,and pAc-β-gal,using Lipofectamine reagent.After incubation for 5 hr,the cells are washed with PBS and then incubated in medium B,in the absence or presence of fatostatin (20 μM) or sterols (10 μg/mL cholesterol and 1 μg/mL 25-hydroxycholesterol).After 20 hr of incubation,an aliquot of the medium is assayed for secreted alkaline phosphatase activity.The cells in each well are lysed and used for measurement of β-galactosidase activities.The alkaline phosphatase activity is normalized by the activity of β-galactosidase.