Etoposide (VP-16)是第一个识别的作为抗癌药物的拓扑异构酶II抑制剂，IC50值为59.2 μM。

Etoposide可以阻断拓扑异构酶II对DNA链重新连接的活性。Etoposide与DNA形成三元复合物，引起DNA链断裂[1]。由于癌细胞的分裂更为迅速，因而该酶在癌细胞中的作用比健康细胞中更重要。因此，etoposide可诱导癌细胞的凋亡[2]。 Etoposide对HepG2和MOLT-3癌细胞具有细胞毒性效应，IC50值分别为30.16 μM和0.051 μM[3]。Etoposide对BGC-823、HeLa和A549癌细胞系的IC50值分别为43.74 ± 5.13、209.90 ± 13.42和139.54 ± 7.05 μM[4]。

参考文献：
[1].  Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010 May 28;17(5):421-33.
[2].  Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15;44(4):441-59.
[3].  Pingaew R, Mandi P, Nantasenamat C, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity. Eur J Med Chem. 2014 May 6;81C:192-203.
[4].  Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10;80:267-77.