Vorinostat (SAHA) is a pan-histone deacetylase (HDAC) inhibitor (IC50=10 nM) with inhibitory activity against HDAC1/2/3/6/7/11. Vorinostat has antitumor activity, induces cell differentiation, blocks the cell cycle and induces apoptosis.

HDAC:~10 nM (cell free)

METHODS: Synovial sarcoma cells SW-982 and chondrosarcoma cells SW-1353 were treated with Vorinostat (0.5-15 μM) for 48 h, and cell viability was measured by MST assay.
RESULTS: Vorinostat inhibited the proliferation of SW-982 and SW-1353 cells in a dose-dependent manner with IC50s of 8.6 μM and 2.0 μM, respectively. [1]
METHODS: Uterine sarcoma cells MES-SA were treated with Vorinostat (3 μM) for 24-72 h. The expression levels of target proteins were detected using Western Blot.
RESULTS: There was no difference in the expression of HDAC1 throughout the treatment period, and HDAC2, 3 and 7 showed significant inhibition of expression by Vorinostat. [2]

METHODS: To detect anti-tumor activity in vivo, Vorinostat (50 mg/kg in HOP-β-CD) was administered intraperitoneally to Nude-Foxn1nu/nu mice bearing uterine sarcoma MES-SA five times per week for twenty-one days.
RESULTS: A reduction in tumor growth of more than 50% was observed in the Vorinostat treatment group compared to the placebo group. [1]
METHODS: To study the effects in an animal model of true erythrocytosis (PV), Vorinostat (200 mg/kg in 50% PEG-400) was injected intraperitoneally into MxCre;Jak2V617F/+ mice five times per week for two weeks.
RESULTS: Vorinostat treatment normalized peripheral blood counts and significantly reduced splenomegaly in Jak2V617F knockout mice.Vorinostat may have therapeutic potential for PV and other JAK2V617F-associated myeloproliferative tumors. [3]

Cells were plated onto 100-mm tissue culture plates at a density of 2 × 10^6 for 48 h and then treated with SAHA or equal concentrations of the vehicle. For longer drug exposure times, medium with drug or vehicle were exchanged every 48 h. For wash-out experiments, cells were treated with SAHA daily for 60–72 h (drug and medium were exchanged at 48 h), then SAHA was washed out and replaced with 10% FCS containing DMEM [3].

Athymic Nude-Foxn1nu/nu mice were used in the present study. They were housed at 22°C at a constant light-dark cycle (12-h light, 12-h dark) and had free access to water and rodent chow (4-5% fat, 21% protein). Twelve weeks old male mice (n = 14) were anesthetized with Isofluran and 5 × 10^6 MES-SA cells were injected subcutaneously into the right flank of the animal. Mice from a control group received placebo containing 300 μl of empty HOP-β-CD (2-hydroxypropyl-β-cyclodextrin) vesicles. Another group of mice received vorinostat dissolved in HOP-β-CD at a concentration of 50 mg/kg/day. Both, empty vesicles and vorinostat were administered intraperitoneally, starting on the day 4 after the injection of MES-SA tumor cells. Mice body weight and tumor size (w2 × l × 0.52; measured by caliper) were estimated twice a week. All mice were treated for 21 days and afterward sacrificed by cervical dislocation. Each tumor was isolated as a whole and different tumor parameters (weight, volume, size, and macroscopic appearance) were determined. Finally, tumor slices were cryopreserved and formalin fixed (4%) for further analyses [1].