PB-100: a potent and selective inhibitor of human BCNU resistant glioblastoma cell multiplication.
Major drawbacks to present-day cancer chemotherapy are its intrinsic lack of selectivity for tumour cells, resulting in severe damage to normal rapidly dividing cells, and the widespread emergence of drug resistance. Here experimental evidence is presented demonstrating that PB-100, a beta-carboline alkaloid, selectively inhibits in vitro multiplication of human BCNU-resistant glioblastoma cells (U251), but has no effect on normal astrocyte (CRL 1656) multiplication. PB-100 activity is dose-dependent. In the presence of ferritin or CaCl2, which are highly mitogenic for glioblastoma cells, higher doses of the alkaloid are required to inhibit multiplication completely. PB-100 is one of several compounds which were selected for their specific action on cancer DNA and cells, together with lack of activity on normal DNA and cells. Both the selectivity of PB-100 and its ability to overcome drug resistance stem from its effect on cancer DNA secondary structure. This activity is described and discussed, and therapeutic applications are mentioned.
Beljanski
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Centre Oncologique et Biologique de Recherches Appliquées Domaine de la Source, St-Prim, France.
Crochet
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Beljanski
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D000970:Antineoplastic Agents / Q000633:toxicity*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002122:Calcium Chloride / Q000494:pharmacology; D002243:Carbolines / Q000633:toxicity*; D002330:Carmustine / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005293:Ferritins / Q000494:pharmacology; D005909:Glioblastoma; D006801:Humans; D007700:Kinetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002243:Carbolines; D004273:DNA, Neoplasm; D004247:DNA; D005293:Ferritins; C034262:flavopereirine; D002122:Calcium Chloride; D002330:Carmustine