CKD-602, a camptothecin derivative, inhibits proliferation and induces apoptosis in glioma cell lines.
CKD-602 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan) is a synthetic water-soluble camptothecin derivative and topoisomerase inhibitor that has been shown to have clinical anticancer effect against ovarian and lung cancer. We studied its anticancer effects on four human glioma cell lines, U87 MG, U343 MG, U251 MG and LN229. Cell viability was quantified by a modified 2-(2-methoxy-4-nitropheyl)-3-(4-nitropheyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and significant time- and dose-dependent cytotoxicity was observed in all cell lines. Susceptibility to CKD-602 at 48 h after treatment varied among the four cell lines and their IC50 value was as follows: 9.07 nM (95% CI 0.18-37.42) for LN229, 14.57 nM (95% CI 0.86-47.33) for U251 MG, 29.13 nM (95% CI 0.35-101.23) for U343 MG, and 84.66 nM (95% CI 34.63-148.25) for U87 MG. CKD-602 induced cell cycle arrest at G2 phase and produced antiproliferative activity and apoptosis in all cell lines. Thus, CKD-602 showed a significant anticancer effect on glioma cells in vitro and is a promising candidate for further studies on malignant gliomas.
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
Young-Yim
YY
Kim
Chul-Kee
CK
Park
Seung-Ki
SK
Kim
Ji-Hoon
JH
Phi
Jin-Hyun
JH
Kim
Chae-Yong
CY
Kim
Kyu-Chang
KC
Wang
Byung-Kyu
BK
Cho
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020128:Inhibitory Concentration 50; D013997:Time Factors; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; C116963:belotecan; D002166:Camptothecin