Cytotoxic mechanism of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd).
The molecular mechanism of cell death induced by 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd: Figure 1), a potent inhibitor of RNA synthesis, was performed using mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd induced the characteristics of apoptosis on these cells, such as morphological changes, DNA fragmentations (Figure 2), and caspase-3-like protease activation. General caspases inhibitor (Z-Asp-CH2-DCB) inhibited these changes and cell death. We also found that ECyd induced DNA and 28S ribosomal RNA (rRNA) fragmentations. Though the mechanisms of rRNA fragmentations haven't revealed, it suggests that translational function of the treated cells should be disturbed. These results indicate that antitumor mechanism of ECyd are characteristics of apoptosis on the cells and rRNA fragmentations is one of the death events resulted inhibition of RNA synthesis.
Wataya
Y
Y
Faculty of Pharmaceutical Science, Okayama University, Tsushima, Japan.
Takenaka
K
K
Yokogawa
T
T
Matsuda
A
A
Sasaki
T
T
Fukushima
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003562:Cytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D005354:Fibrosarcoma; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity*; D012339:RNA, Ribosomal, 28S / Q000235:genetics / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D012339:RNA, Ribosomal, 28S; D003562:Cytidine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases