Homoharringtonine is a protein synthesis inhibitor and a cytotoxic alkaloid, originally isolated from the evergreen tree Cephalotaxus hainanensis. It is often used in the research of lung cancer and breast cancer[1].
Homoharringtonine (0-36.7nM; 0-96h) effectively inhibits the growth and viability of human acute myeloid leukemia cells and promotes cell cycle arrest, apoptosis and differentiation[1]. Homoharringtonine (0-400nM; 24-48h) inhibits the proliferation of melanoma cells A375 and B16F10 in vitro by inducing DNA damage, apoptosis, and G2/M cell cycle arrest[2]. Homoharringtonine (20nM; 0-48h) suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma[3].
In an A375 cell xenograft mice model, Homoharringtonine (1mg/kg; 10 days) can treat mice FLT3 mutant acute myeloid leukemia by targeting the SP1/TET1 pathway in acute myeloid leukemia cells and downregulating overall 5hmC levels[1]. Homoharringtonine (2.5mg/kg; two-day intervals; 20 days) inhibits the growth of lung tumor cells in mice carrying Kras mutations in vivo by altering cytokine expression in immune cells through inhibition of protein synthesis[4].
References：
[1]. Li C, Dong L, Su R, et al. Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC[J]. haematologica, 2020, 105(1): 148.
[2]. Tang J, Li G, Zhang T, et al. Homoharringtonine inhibits melanoma cells proliferation in vitro and vivo by inducing DNA damage, apoptosis, and G2/M cell cycle arrest[J]. Archives of Biochemistry and Biophysics, 2021, 700: 108774.
[3]. Zhu, Man et al. “Homoharringtonine suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma.” Cell death & disease vol. 11,8 632. 14 Aug. 2020.
[4]. Weng T Y, Wu H F, Li C Y, et al. Homoharringtonine induced immune alteration for an efficient anti-tumor response in mouse models of non-small cell lung adenocarcinoma expressing Kras mutation[J]. Scientific reports, 2018, 8(1): 8216.
Homoharringtonine是一种蛋白质合成抑制剂和细胞毒性生物碱，最初从常绿树海南三尖杉中分离得到。Homoharringtonine常用于肺癌和乳腺癌的研究[1]。
Homoharringtonine（0-36.7nM；0-96h）可有效抑制人急性髓系白血病细胞的生长和活力，并促进细胞周期停滞、凋亡和分化[1]。Homoharringtonine（0-400nM；24-48h）通过诱导DNA损伤、凋亡和G2/M细胞周期停滞，抑制黑色素瘤细胞A375和B16F10体外增殖[2]。Homoharringtonine（20nM；0-48h）通过调节肝细胞癌中EphB4介导的β-catenin丢失来抑制肿瘤增殖和迁移[3]。
在A375细胞异种移植小鼠模型中，Homoharringtonine（1mg/kg；10 days) 可通过靶向急性髓系白血病细胞中的SP1/TET1通路并下调整体5hmC水平来治疗小鼠 FLT3 突变型急性髓系白血病[1]。Homoharringtonine（2.5mg/kg；两天间隔；20 days）可通过抑制蛋白质合成来改变免疫细胞中的细胞因子表达，从而抑制体内携带Kras突变的小鼠的肺肿瘤细胞生长[4]。