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Selective Toxicity of a Highly Potent Camptothecin Analogue: A Pilot Study with Glioblastoma Multiforme Cells
Garret Yount1, Liliana Soroceanu1, Hui-Juan Wang1
1California Pacific Medical Center Research Institute, San Francisco, CA, U.S.A.
Background/Aim:
We developed a novel camptothecin analogue, CPT417, that yields reduced toxicity compared to other analogues used in chemotherapeutic regimens. In this pilot study, we assessed the activity of CPT417 against glioblastoma multiforme (GBM) cells and glioma stem cells.
Materials And Methods:
The human U251 GBM cell line and normal human astrocytes were cultured in parallel for clonogenic survival analysis following exposure to increasing concentrations of CPT417. Cell viability of a glioma stem cell line was assessed 5 days after exposure to a range of CPT417 concentrations.
Results:
CPT417 completely inhibited clonogenic survival of GBM cells at 10 nM, whereas this concentration only inhibited astrocytes by approximately 50%. Cell viability analysis of glioma stem cell cultures yielded a half-maximal response at 15 nM.
Conclusion:
CPT417 acts selectively against GBM cells at concentrations that are at least an order of magnitude below reported values for related alkylating agents in clinical use.
