Size : 100mg
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Etoposide (VP-16) is the first agent recognized as a topoisomerase II inhibitor of anticancer drug with IC50 of 59.2 μM.
The activity of the topoisomerase II enzyme on re-ligation of DNA strands is interrupted by etoposide. A ternary complex with DNA is formed by etoposide, and causes DNA strands to break [1]. The enzyme was more important in cancer cell than healthy cells, because cancer cells divided more rapidly. So etoposide induced apoptosis of the cancer cells [2]. Etoposide exhibited cytotoxic activity against HepG2 and MOLT-3 cancer cells with IC50 of 30.16 μM and 0.051μM [3]. The IC50 values of etoposide against the tumor cell lines of BGC-823, HeLa, and A549 were 43.74 ± 5.13, 209.90 ± 13.42, and 139.54 ± 7.05 μM, respectively [4].
References:[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.
Topoisomerase II activity assay
Nuclear extracts are prepared, and nuclei are isolated. The activity of topoisomerase II is calculated from the percentage of decatenation obtained. Tritiated kinoplast DNA (KDNA 0.22 μg) is used as a substrate. Etoposide and topoisomerase II are incubated for 30 min at 37°C and are stopped with 1% sodium dodecyl sulfate (SDS) and proteinase K (100 μg/mL). The percentages of decatenation and inhibition of topoisomerase II by Etoposide are obtained.
Cell lines
BGC-823, HeLa and A549 cells
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions
0.5, 1, 10, 20, 50, 100, 200 and 500 μM; 2 d
Applications
The IC50 values of Etoposide against the tumor cell lines of BGC-823, HeLa and A549 were 43.74 ± 5.13 μM, 209.90 ± 13.42 μM and 139.54 ± 7.05 μM, respectively.
Animal models
Murine angiosarcoma xenografts ISOS-1
Dosage form
2.5, 5, 10 mg/kg; i.p.; every day for 5 days
The dose of 10 mg/kg Etoposide (i.p.) inhibited murine angiosarcoma cell ISOS-1 tumors.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1] Beauchesne P, Bertrand S, N'guyen MJ, Christianson T, Dore JF, Mornex F, Bonner JA. Etoposide sensitivity of radioresistant human glioma cell lines. Cancer Chemother Pharmacol. 1998; 41 (2): 93-7.
[2] 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.
[3] Ma G1, Masuzawa M, Hamada Y, Haraguchi F, Tamauchi H, Sakurai Y, Fujimura T, Katsuoka K. Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone. J Dermatol Sci. 2000 Nov; 24 (2): 126-33.