Roxithromycin and clarithromycin, 14-membered ring macrolides, potentiate the antitumor activity of cytotoxic agents against mouse B16 melanoma cells.
We previously reported antiangiogenic activity of roxithromycin and clarithromycin, 14-membered ring macrolide antibiotics. In the present study, we examined the antitumor effects of roxithromycin and clarithromycin, alone and in combination with several cytotoxic drugs, on mouse B16BL6 melanoma cells in vivo and in vitro. Both roxithromycin and clarithromycin potentiated the inhibition of tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin and vindesine in vivo. However, neither roxithromycin nor clarithromycin, altered the cytotoxicity of 4-hydroperoxycyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin or vindesine in an in vitro cell proliferation assay. These results suggest that the antiangiogenic activity of roxithromycin and clarithromycin may provide beneficial effects in combination with cytotoxic therapies against solid tumors.
Yatsunami
J
J
Department of Internal Medicine, Saga Medical School, Nabeshima, Japan. yatsunam@post.saga-med.ac.jp
Fukuno
Y
Y
Nagata
M
M
Tsuruta
N
N
Aoki
S
S
Tominaga
M
M
Kawashima
M
M
Taniguchi
S
S
Hayashi
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D017291:Clarithromycin / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D015575:Roxithromycin / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000008:administration & dosage
D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D017291:Clarithromycin; D002945:Cisplatin; D014751:Vindesine; C011272:perfosfamide