Trichostatin A (TSA) is A potent histone deacetylase (HDAC) inhibitor and an antifungal antibiotic with an IC50 value of 1.8 nM for HDAC[1], which has the properties of inhibiting cell growth and inducing cell differentiation.
Trichostatin A (TSA) can arrest cells in G1 and G2 phases, induce cell differentiation, and restore transformed morphology of cultured cells. Trichostatin A (TSA) inhibits proliferation of breast cancer cells in human breast cancer cell linesand resulted in hyperacetylation of histone H4[1]. Trichostatin A (TSA) promotes apoptosis and radiation-induced DNA damage in mitotic G2 gap 2 (G2/M) -arrested cells. Trichostatin A (TSA) may directly participate in DNA damage in esophageal cancer cells by reducing the acetylation of growth-associated genomic protein H3[2].Pre-treatment of RLE-6TN cells with Trichostatin A (TSA) inhibited radiation-induced EMT-like morphological alterations including elevated protein level of α-SMA and Snail, reduction of E-cadherin expression, enhanced phosphorylation of GSK3β and ERK1/2, increased generation of ROS[3].The invasive and migratory abilities of MCF-7 cells were suppressed significantly upon treatment with Trichostatin A (TSA). Treatment with Trichostatin A (TSA) led to an increased expression level of E-cadherin, and decreased expression of vimentin and, in MCF-7 cells[4]. Trichostatin A (TSA) enhanced the radiosensitivity of colon cancer cells, apoptotic cell death induced by radiation was enhanced by Trichostatin A (TSA) treatment. Trichostatin A (TSA) also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells[5].
Trichostatin A (TSA) had pronounced antitumor activity in vivo when administered to 16 animals at a dose of 500 microg/kg by injection daily for 4 weeks compared with 14 control animals. Furthermore, Trichostatin A (TSA) did not cause any measurable toxicity in doses of up to 5 mg/kg by injection. Trichostatin A (TSA) has significant antitumor activity in vivo The antitumor activity of Trichostatin A (TSA) is attributed to differentiation induction[1].In porcine SCNT embryos,Chaetocin, Trichostatin A (TSA), and the combination significantly increased the cleavage and blastocyst formation rate, hatching/hatched blastocyst rate, and cell numbers and survival rate. The combined treatment improved the rate of development to blastocysts more so than chaetocin or Trichostatin A (TSA) alone[6].This decreased emotionality observed in stress-maladaptive mice was significantly recovered by chronic treatment with Trichostatin A (TSA) 2 h before daily exposure to restraint stress, which confirmed the development of stress adaptation. HDAC inhibitor Trichostatin A (TSA) may have a beneficial effect on stress adaptation by affecting 5-HT neural function in the brain and alleviate the emotional abnormality under conditions of excessive stress[7].
References:
[1]: Vigushin DM, Ali S, et,al. Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. Clin Cancer Res. 2001 Apr;7(4):971-6. PMID: 11309348.
[2]: Wang S, Song M, et,al. Trichostatin A enhances radiosensitivity and radiation-induced DNA damage of esophageal cancer cells. J Gastrointest Oncol. 2021 Oct;12(5):1985-1995. doi: 10.21037/jgo-21-560. PMID: 34790366; PMCID: PMC8576220.
[3]: Nagarajan D, Wang L, et,al. Trichostatin A inhibits radiation-induced epithelial-to-mesenchymal transition in the alveolar epithelial cells. Oncotarget. 2017 Oct 9;8(60):101745-101759. doi: 10.18632/oncotarget.21664. PMID: 29254201; PMCID: PMC5731911.
[4]: Wang X, Chen S, et,al. Trichostatin A reverses epithelial-mesenchymal transition and attenuates invasion and migration in MCF-7 breast cancer cells. Exp Ther Med. 2020 Mar;19(3):1687-1694. doi: 10.3892/etm.2020.8422. Epub 2020 Jan 3. PMID: 32104221; PMCID: PMC7027139.
[5]: He G, Wang Y, et,al. Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation. Tumour Biol. 2014 Feb;35(2):1003-11. doi: 10.1007/s13277-013-1134-z. PMID: 24122231.
[6]: Jeong PS, Yang HJ, et,al. Combined Chaetocin/Trichostatin A Treatment Improves the Epigenetic Modification and Developmental Competence of Porcine Somatic Cell Nuclear Transfer Embryos. Front Cell Dev Biol. 2021 Oct 6;9:709574. doi: 10.3389/fcell.2021.709574. PMID: 34692674; PMCID: PMC8526721.
[7]: Kimijima H, Miyagawa K, et,al. Trichostatin A, a histone deacetylase inhibitor, alleviates the emotional abnormality induced by maladaptation to stress in mice. Neurosci Lett. 2022 Jan 1;766:136340. doi: 10.1016/j.neulet.2021.136340. Epub 2021 Nov 10. PMID: 34774702.
Trichostatin A (TSA) 是一种有效的组蛋白脱乙酰酶 (HDAC) 抑制剂和抗真菌抗生素，对 HDAC[1] 的 IC50 值为 1.8 nM，具有抑制细胞生长和诱导细胞分化。
曲古抑菌素 A (TSA) 可以将细胞阻滞在 G1 和 G2 期，诱导细胞分化，并恢复培养细胞的转化形态。曲古抑菌素 A (TSA) 抑制人乳腺癌细胞系中乳腺癌细胞的增殖，并导致组蛋白 H4 过度乙酰化[1]。曲古抑菌素 A (TSA) 促进有丝分裂 G2 间隙 2 (G2/M) 阻滞细胞的细胞凋亡和辐射诱导的 DNA 损伤。曲古抑菌素A（TSA）可能通过降低生长相关基因组蛋白H3[2]的乙酰化水平直接参与食管癌细胞DNA损伤。曲古抑菌素A（TSA）预处理RLE-6TN细胞) 抑制辐射诱导的 EMT 样形态学改变，包括 α-SMA 和 Snail 蛋白水平升高、E-钙粘蛋白表达降低、GSK3β 和 ERK1/2 磷酸化增强、ROS 生成增加[3].MCF-7 细胞的侵袭和迁移能力在用曲古抑菌素 A (TSA) 处理后被显着抑制。在 MCF-7 细胞中用曲古抑菌素 A (TSA) 处理会导致 E-cadherin 表达水平升高，波形蛋白和 vimentin 表达降低[4]。曲古抑菌素A (TSA) 增强了结肠癌细胞的放射敏感性，曲古抑菌素A (TSA) 处理增强了辐射诱导的凋亡细胞死亡。曲古抑菌素A（TSA）也诱导结肠癌细胞自噬反应，抑制自噬导致细胞凋亡，增强结肠癌细胞的放射敏感性[5]。
与 14 只对照动物相比，通过每天注射 500 微克/公斤的剂量给 16 只动物给药 4 周，曲古抑菌素 A (TSA) 在体内具有显着的抗肿瘤活性。此外，曲古抑菌素 A (TSA) 在高达 5 mg/kg 的注射剂量下未引起任何可测量的毒性。 Trichostatin A (TSA) 在体内具有显着的抗肿瘤活性 Trichostatin A (TSA) 的抗肿瘤活性归因于分化诱导[1]。在猪SCNT 胚胎中，Chaetocin、Trichostatin A (TSA) 和该组合显着提高了卵裂和囊胚形成率、孵化/孵化囊胚率以及细胞数量和存活率。与单独使用毛壳菌素或曲古抑菌素 A (TSA) 相比，联合治疗更能提高胚泡的发育速度[6]。在应激适应不良小鼠中观察到的这种情绪下降通过曲古抑菌素 A 的长期治疗显着恢复(TSA) 每天暴露于束缚压力前 2 小时，这证实了压力适应的发展。 HDAC 抑制剂曲古抑菌素 A (TSA) 可能通过影响大脑中的 5-HT 神经功能对应激适应产生有益作用，并减轻过度应激条件下的情绪异常[7]。