Trichostatin A (TSA) is an antifungal antibiotic derived from Streptomyces that inhibits mammalian histone deacetylase (HDAC). TSA inhibits the eukaryotic cell cycle during the beginning of the growth stage. Trichostatin A (TSA) can be used to alter gene expression by interfering with the removal of acetyl groups from histones (histone deacetylases, HDAC) and therefore altering the ability of DNA transcription factors to access the DNA molecules inside chromatin. It is a member of a larger class of histone deacetylase inhibitors (HDIs or HDACIs) that have a broad spectrum of epigenetic activities. Trichostatin A has also been shown to inhibit both G1- and G2-phases of the mammalian cell cycle and has been tested for use as a potential anticancer agent.
bioRxiv. 2023 May 30.
Imaging the microscopic viscoelastic anisotropy in living cells
Trichostatin A purchased from AbMole
University of Otago. 2019.
Transcriptional effects of mood stabiliser drugs in a serotonergic cell line
Trichostatin A purchased from AbMole
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Source | Oncotarget (2017). Figure 2. Trichostatin A |
| Method | Western blotting | |
| Cell Lines | RLE-6TN cells | |
| Concentrations | 100 nM | |
| Incubation Time | 72 h | |
| Results | Snail was significantly increased in irradiated group which was effectively modulated by the treatment of TSA, as we observed from the data of western blot |
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Source | Oncotarget (2017). Figure 1. Trichostatin A |
| Method | Western blotting | |
| Cell Lines | RLE-6TN cells | |
| Concentrations | 100 nM | |
| Incubation Time | 72 h | |
| Results | TSA led to a significant modification in the protein and gene expressions of both E-cadherin and α-SMA in cells collected at 72 h after irradation. |
| Cell Experiment | |
|---|---|
| Cell lines | MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3 cell lines |
| Preparation method | Cell Proliferation Assay. Stock cultures of breast cancer cell lines MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3 (American Type Culture Collection, Rockville, MD) were grown in DMEM containing 10% (v/v) FCS, 2 mM L-glutamine, 100 units/ml penicillin, and 100 mg/ml streptomycin at 37°C in 5% CO2 humidified atmosphere. Cells were counted in a hemocytometer after detachment using 0.25% (w/v) trypsin in Dulbecco’s PBS without Ca21 or Mg21 (DPBS; Sigma-Aldrich) containing 0.02% (w/v) EDTA. Viability was determined by trypan blue exclusion. For each cell line, cells were seeded in 96-well microtiter plates at optimal densities determined in prior experiments to ensure exponential growth for the duration of the assay. After a 24-h preincubation, growth medium was replaced with experimental medium containing TSA at final concentrations ranging from 10-12 M to 10-5 M in log dilutions and 0.1% (v/v) ethanol, or growth medium containing 0.1% (v/v) ethanol as a vehicle control. After 96 h incubation, cell proliferation was estimated using the sulforhodamine B colorimetric assay (11), and the results are expressed as the mean 6 SD for six replicates as a percentage of vehicle control (taken as 100%). |
| Concentrations | 10-12 M to 10-5 M |
| Incubation time | 96 h |
| Animal Experiment | |
|---|---|
| Animal models | Inbred virgin female (Ludwig/Wistar/ Olac) rats bearing tumors induced with NMU model |
| Formulation | DMSO |
| Dosages | 500 µg/kg TSA in50 µl DMSO twice weekly for 4 weeks |
| Administration | s.c. injection |
| Molecular Weight | 302.37 |
| Formula | C17H22N2O3 |
| CAS Number | 58880-19-6 |
| Solubility (25°C) | DMSO 23 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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