Romidepsin (FK228, depsipeptide) is an effective and selective histone deacetylase (HDAC) inhibitor, with IC50 values of 36nM, 47nM, 510nM, and 1.4μM for HDAC1, HDAC2, HDAC4, and HDAC6, respectively [1-2]. HDAC is a type of epigenetic regulator, and the HDAC1 is expressed in many tumor types [3]. Romidepsin has anti-tumor activity and can induce cell cycle arrest, cell differentiation, apoptosis, and gene expression changes in malignant tumor cells [4].
In vitro, Romidepsin (0.5-30ng/mL; 72h) treatment can dose-dependently reduce the cell viability of neuroblastoma cell lines (NB), and the cell morphology shows a round, denser, and non-adherent state. In different NB cell lines, the IC50 range of Romidepsin is 1-6.5ng/mL [5]. Romidepsin (0-60nM; 0-48h) can induce G2/M phase cell cycle arrest in HCC cells in a time- and dose-dependent manner and promote cell apoptosis, increasing the expression of c-caspase-3, c-caspase-9, and c-PARP proteins [6].
In vivo, Romidepsin (1-1.7mg/kg/day; injected once every 3 or 4 days, for a total of five times; i.p.) significantly inhibits the growth of xenograft mouse KCNR tumors. Within 6 hours of a single dose, the p21 level in the mouse tumors increased nearly 7 times compared to the control group, and reached 25 times at 24 hours [5]. Romidepsin (0.5 and 1mg/kg/day; once every 3 days, for 21 days; i.p.) significantly inhibits tumor growth in Huh7 tumor-bearing mice and increases the expression of p-cdc25C, ki67, c-caspase-3, and c-PARP, and reduces the expression of Ki-67 [6].
References:
[1] Karen M VanderMolen, William McCulloch, Cedric J Pearce and Nicholas H Oberlies. Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. The Journal of Antibiotics 2011: 64, 525-531
[2] Furumai R, Matsuyama A, Kobashi N, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res. 2002;62(17):4916-4921.
[3] Pojani E, Barlocco D. Romidepsin (FK228), A Histone Deacetylase Inhibitor and its Analogues in Cancer Chemotherapy. Curr Med Chem. 2021;28(7):1290-1303.
[4] Jyoti Panicker, Zhijie Li, Christine McMahon, et al. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells. Cell Cycle 2010 9:9, 1830-1838.
[5] Panicker J, Li Z, McMahon C, et al. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells. Cell Cycle. 2010;9(9):1830-1838.
[6] Sun WJ, Huang H, He B, et al. Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells. Biochem Pharmacol. 2017;127:90-100.
Romidepsin (FK228, depsipeptide)是一种有效且选择性的组蛋白去乙酰化酶（HDAC）抑制剂，抑制HDAC1，HDAC2，HDAC4和HDAC6的IC50值分别为36nM，47nM，510nM和1.4μM [1-2]。HDAC是一类表观遗传调节因子，HDAC1在许多肿瘤类型中表达 [3]。Romidepsin具有抗肿瘤活性，能诱导恶性肿瘤中的细胞周期停滞、细胞分化、凋亡和基因表达改变 [4]。
在体外，Romidepsin（0.5–30ng/mL; 72h）处理能够剂量依赖性降低神经母细胞瘤细胞系（NB）的细胞活力，并且细胞形态表现为圆形、更密集且不贴壁的状态。在不同的NB细胞系中，Romidepsin的IC50范围为1-6.5ng/mL [5]。Romidepsin（0-60nM; 0-48h）能够以时间和剂量依赖性方式诱导HCC细胞中G2/M期细胞周期停滞，并促进细胞凋亡，增加了细胞中c-caspase-3、c-caspase-9和c-PARP蛋白的表达 [6]。
在体内，Romidepsin（1-1.7mg/kg/day; 每3或4天注射一次，共五次; i.p.）显著抑制异种移植小鼠KCNR肿瘤的生长。单剂量给药6小时内，小鼠肿瘤中的p21水平与对照组相比增加了近7倍，并在24小时达到25倍 [5]。Romidepsin（0.5和1mg/kg/day; 每3天一次, 21天; i.p.）显著抑制Huh7荷瘤小鼠的肿瘤生长，并升高了肿瘤中p-cdc25C、ki67、c-caspase-3和c-PARP的表达，以及降低Ki-67的表达 [6]。