Methylcobalamin inhibits fibroblast growth factor-8 stimulated proliferation and induces apoptosis in Shionogi carcinoma cells.
SC-3 cells, an androgen-dependent mouse mammary carcinoma cell line, in response to androgen stimuli, induces the secretion of fibroblast growth factor (FGF-8), which in turn increases the proliferation of these cells. We have shown previously that methylcobalamin (MeCbl) decreases the levels of FGF-8 mRNA in SC-3 cells stimulated by testosterone, inhibiting the proliferation of SC-3 cells and inducing apoptosis. In the present study, we analyzed the effects of MeCbl on SC-3 cell proliferation in response to exogenous addition of FGF-8. Thymidine incorporation showed a significant decrease in SC-3 cells cultured with MeCbl. Immunocytochemistry for single-stranded DNA (ssDNA) and DNA fragmentation analysis demonstrated that MeCbl induced apoptosis in SC-3 cells, even in the presence of FGF-8. These results show that the addition of FGF-8 stimulates the proliferation of SC-3 cells under the androgen-depleted condition and that MeCbl might be able to interfere with FGF-8 action.
Goto
Greicy H
GH
Dept. of Pathology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-Chome, Higashinari, Osaka, Japan.
Katayama
Hiroshi
H
Tanigaki
Yumiko
Y
Fushiki
Shinji
S
Nishizawa
Yoshio
Y
Nishizawa
Yasuko
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D006131:Growth Inhibitors; D051524:Fibroblast Growth Factor 8; D004247:DNA; C019476:mecobalamin; D014805:Vitamin B 12; D013936:Thymidine