Objective: CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin), a novel synthetic water soluble camptothecin derivative, has been reported to have greater anticancer effect and better therapeutic index compared with other topoisomerase inhibitor analogues such as CPT-11 or topotecan in ovarian or lung cancer. We studied therapeutic effect of the CKD-602 on human glioma cell lines to assess the feasibility as an anticancer drug for malignant glioma.

Materials and Methods: Two human glioma cells lines, U87 MG and U251 MG, were treated with CKD-602 in vitro. We examined the effect of CKD-602 on topoisomerase expression, cell viability, cell cycle distribution, proliferative activity, and cellular apoptosis.

Result: Western blot analysis confirmed the inhibitory actions of CKD-602 on topoisomerase expression in both cell lines. CKD-602 showed conspicuous cytotoxic effect cell lines in time- and dose-dependant manner. The calculated IC50s were 879.08 nM (95% CI: 418.50-2689.94) on U87 MG and 54.76 nM (95%CI: 9.27-126.64) on U251 MG at 48 hours after treatment. CKD-602 induced cell cycle arrest at S and G2 phase.

We could also observe the anti-proliferative activity and the induction of apoptosis in both cell lines. The effect of CKD-602 was more potent in U251 MG cells (p53 mutant type) than U87 MG cells (p53 wild type).

Conclusion: This study suggests that the CKD-602 has a significant anticancer effect on glioma cells in vitro. CKD-602 is a promising candidate for further preclinical and clinical studies on glial tumors.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA