Cellular uptake as a determinant of cytotoxicity of quaternized ellipticines to human brain tumor cells.
The quaternized ellipticine derivative, 9-methoxy-N2-methylellipticinium acetate (MMEA), is representative of a group of ellipticinium compounds found preferentially cytotoxic to human brain tumor cell lines comprising a subpanel of the U.S. National Cancer Institute (NCI)'s in vitro "disease-oriented" anticancer drug discovery screen. The present studies indicate that the accumulation and cytotoxicity of MMEA in these susceptible cells are mediated in part by a cellular transport process having substrate and inhibitor specificities similar to those found in glial-derived cells which presumably comprise part of the structural (non-neuronal) elements of normal brain.
Vistica
D T
DT
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201.
Kenney
S
S
Hursey
M L
ML
Boyd
M R
MR
D000970:Antineoplastic Agents; D001667:Binding, Competitive; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004611:Ellipticines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D012110:Reserpine / Q000378:metabolism / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004611:Ellipticines; D012110:Reserpine