Etoposide (VP-16) is a nonspecific inhibitor of topoisomerase II with an IC50 value of 59.2μM[1]. Etoposide inhibits DNA synthesis by inhibiting topoisomerase II activity, and can induce cell cycle arrest, apoptosis, and autophagy[2].
In vitro, treatment of HCT116 FBXW7+/+, FBXW7−/−, and p53−/− cells with Etoposide (0-1μM) for 72h inhibited cell growth in a dose-dependent manner with IC50 values of 0.945μM, 0.375μM, and 1.437μM, respectively[3]. Treatment of adherent C33a cells with Etoposide (5μM) for 48h induced marginal cell apoptosis and cell cycle G2/M arrest[4].
In vivo, Etoposide (80mg/kg) was injected intraperitoneally into adult Smc5 flox/del, Stra8-Cre cKO mice. After 8 days of exposure, spermatocyte defects were observed in the mice, with an increase in the number of enlarged round spermatids with two acrosomes and extra chromosomes [5]. Etoposide (50mg/kg) was injected intraperitoneally into mice inoculated with 3LL lung cancer cells, inducing the host immune system to recognize 3LL cells and increasing the survival rate of the mice to 60% [6].
References:
[1] Sudo K, Konno K, Shigeta S, et al. Inhibitory effects of podophyllotoxin derivatives on herpes simplex virus replication[J]. Antiviral Chemistry and Chemotherapy, 1998, 9(3): 263-267.
[2] Xu D, Cao J, Qian S, et al. 5k, a novel β-O-demethyl-epipodophyllotoxin analogue, inhibits the proliferation of cancer cells in vitro and in vivo via the induction of G2 arrest and apoptosis[J]. Investigational new drugs, 2011, 29: 786-799.
[3] Cui D, Xiong X, Shu J, et al. FBXW7 confers radiation survival by targeting p53 for degradation[J]. Cell reports, 2020, 30(2): 497-509. e4.
[4] Bristol M L, Wang X, Smith N W, et al. DNA damage reduces the quality, but not the quantity of human papillomavirus 16 E1 and E2 DNA replication[J]. Viruses, 2016, 8(6): 175.
[5] Hwang G, Verver D E, Handel M A, et al. Depletion of SMC5/6 sensitizes male germ cells to DNA damage[J]. Molecular biology of the cell, 2018, 29(25): 3003-3016.
[6] Slater L M, Stupecky M, Sweet P, et al. Etoposide induction of tumor immunity in Lewis lung cancer[J]. Cancer chemotherapy and pharmacology, 2001, 48: 327-332.
Etoposide（VP-16）是一种非特异性拓扑异构酶II（Topoisomerase II）抑制剂，IC50值为59.2 μM[1]。Etoposide通过抑制拓扑异构酶II活性而抑制DNA合成，可诱导细胞周期停滞、凋亡和自噬[2]。
在体外，Etoposide（0-1μM）处理HCT116 FBXW7+/+, FBXW7−/−, p53−/−细胞72h，以剂量依赖性方式抑制了细胞生长，IC50分别为0.945 μM、0.375 μM，和1.437 μM[3]。Etoposide（5μM）处理贴壁C33a细胞48h，诱导了边缘细胞凋亡以及细胞周期G2/M停滞[4]。
在体内，Etoposide（80mg/kg）通过腹膜内注射处理成年Smc5 flox/del、Stra8-Cre cKO小鼠，暴露8天后，使小鼠精子细胞发生缺陷，增大的圆形精子细胞数量增加，且具有2个顶体和多余染色体[5]。Etoposide（50mg/kg）通过腹膜内注射治疗接种了3LL肺癌细胞的小鼠，诱导宿主免疫系统识别3LL细胞，使小鼠存活率达到60%[6]。