Induction of apoptosis by enediyne antitumor antibiotic C1027 in HL-60 human promyelocytic leukemia cells.
C1027, a new macromolecular antitumor antibiotic with an enediyne chromophore, displays extremely potent cytotoxicity against cancer cells. HL-60 human promyelocytic leukemia cells treated with C1027 (0.1-10 nM) for 2 hours resulted in morphological changes, including Hoechst 33342-stained condensed nuclei, condensation of nuclear chromatin, and nuclear fragmentation. Agarose gel electrophoresis of C1027-treated HL-60 cells showed a typical ladder-like pattern of DNA fragments. In addition, the apoptotic DNA peak of propidium iodide-stained nuclei was revealed by flow cytometry. Treatment of HL-60 cells with C1027 (5 nM) induced apoptosis in up to 79% of the cells. The results suggest that C1027 may exert antitumor activity by triggering apoptosis.
Jiang
B
B
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tiantan, Beijing.
Li
D D
DD
Zhen
Y S
YS
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053281:Enediynes; D005434:Flow Cytometry; D006248:Harringtonines / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D009336:Necrosis; D010455:Peptides; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D053281:Enediynes; D006248:Harringtonines; D010455:Peptides; C062500:harringtonin; C058024:C 1027