CC-1065 (NSC 298223), a most potent antitumor agent: kinetics of inhibition of growth, DNA synthesis, and cell survival.
CC-1065 (NSC 298223) is the most cytotoxic agent tested against cells in culture in our laboratory. The 50% lethal doses for exponentially growing B16 melanoma and Chinese hamster ovary cells were 0.44 and 0.14 ng/ml, respectively, as compared to 35 and 500 ng/ml for Adriamycin. In the human tumor-cloning assay, 1-hr exposure to CC-1065 (0.1 ng/ml) caused greater than or equal to 50% lethality in a broad spectrum of tumors. The dose-survival curves for B16 and Chinese hamster ovary cells were characterized by an initial shoulder followed by an exponential decline with increasing dose. CC-1065 was more lethal to exponentially growing B16 cells (50% lethal dose = 0.44 ng/ml) than to plateau-phase cells (50% lethal dose = 1.2 ng/ml). CC-1065 inhibited DNA synthesis much more than did RNA or protein synthesis. After a 2-hr incubation with drug, inhibition of DNA synthesis was low immediately (0 hr) after drug exposure and reached maximum inhibition about 20 hr later. The doses for 50% inhibition of growth (0.18 ng/ml), survival (0.44 ng/ml), and DNA synthesis (0.15 ng/ml) were in the same range, whereas RNA synthesis was inhibited 50% at a much higher dose (5 ng/ml).
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001769:Blood; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D000080890:Duocarmycins; D005260:Female; D006801:Humans; D007211:Indoles; D007700:Kinetics; D007933:Leucomycins / Q000494:pharmacology*; D008545:Melanoma; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000473:pathology*; D010053:Ovary; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D004273:DNA, Neoplasm; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C018782:CC 1065