Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia - PubMed (original) (raw)

HDAC inhibitors and resveratrol dose-dependently increase luciferase reporter activity. The Neuro-2a luciferase reporter cell line used for screening was also utilized in follow-up experiments. A, dose-response relationships for HTS hits SAHA (●), resveratrol (△), and leflunomide (■). EC50 values were 0.51 μ

m

for SAHA and 0.24 μ

m

for resveratrol. B, dose-response relationships for HDAC inhibitors M344 (●), PTACH (△), and trichostatin A (TSA; □). C, dose-response relationships for class I specific HDAC inhibitors MS-275 (●) and sodium valproate (△). D, selective HDAC inhibitors MC1568 (class II selective; ●), tubacin (HDAC6-specific; ■), tubastatin A (HDAC6-specific; △), and droxinostat (HDAC3-, HDAC6-, and HDAC8-selective; ♢) did not increase GRN promoter reporter activity. E, SAHA and resveratrol have additive effects. Resveratrol concentrations tested are shown on the x axis. SAHA concentrations tested are noted next to the dose-response curves. ●, resveratrol alone; △, resveratrol + 0.1 μ

m

SAHA; ■, resveratrol + 0.3 μ

m

SAHA; ♢, resveratrol + 0.5 μ

m

SAHA. F, SAHA and resveratrol have additive effects. SAHA concentrations tested are shown on the x axis. Resveratrol concentrations tested are noted next to the dose-response curves. ●, SAHA alone; △, SAHA + 0.1 μ

m

resveratrol; ■, SAHA + 1 μ

m

resveratrol.