Re-evaluation of tumor-specific cytotoxicity of mitomycin C, bleomycin and peplomycin.
Three antitumor antibiotics, mitomycin C, bleomycin sulfate and peplomycin sulfate, were compared for their tumor-specific cytotoxicity, using human oral squamous cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and NA), human promyelocytic leukemic cell line HL-60 and human normal oral cell types (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Among these three compounds, mitomycin C showed the highest tumor-specificity, due to its higher cytotoxic activity against human oral tumor cell lines than bleomycin and peplomycin. However, there was considerable variation of drug sensitivity among the six tumor cell lines. Mitomycin C induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in HL-60 cells only after 24 h. On the other hand, mitomycin C induced no clear-cut DNA fragmentation in HCS-2 cells, although it activated caspase-3, -8 and -9 to a slightly higher extent. Western blot analysis demonstrated that mitomycin C did not induce any apparent change in the intracellular concentration of anti-apoptotic protein (Bcl-2) and pro-apoptotic proteins (Bax, Bad). Electron microscopy of mitomycin C-treated HL-60 cells showed intact mitochondria (as regards to integrity and size) and cell surface microvilli, without production of an apoptotic body or autophagosome, at an early stage after treatment. The present study suggests the incomplete induction of apoptosis or the induction of another type of cell death by mitomycin C treatment.
Sasaki
Masahiro
M
Division of Oral Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Okamura
Masahiko
M
Ideo
Atsushi
A
Shimada
Jun
J
Suzuki
Fumika
F
Ishihara
Mariko
M
Kikuchi
Hirotaka
H
Kanda
Yumiko
Y
Kunii
Shiro
S
Sakagami
Hiroshi
H
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D017663:Peplomycin / Q000494:pharmacology*; D014466:Ultraviolet Rays
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D016685:Mitomycin; D017663:Peplomycin; D020169:Caspases