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Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells

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Abstract

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.

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Authors and Affiliations

  1. The Department of Internal Medicine, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501, Japan

    Jun Yatsunami, Yuji Fukuno, Masaki Nagata, Masaki Tominaga, Shigehisa Aoki, Michihiro Kawashima & Shin-ichiro Hayashi

  2. Research Institute for Disease of the Chest, Faculty of Medicine, Kyushu University, 3-1-1, Maidashi Higashiku, Fukuoka, 812-8582, Japan

    Nobuko Tsuruta

  3. Research Center on Aging and Adaptation, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-862, Japan

    Shun'ichiro Taniguchi

Authors
  1. Jun Yatsunami
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  2. Yuji Fukuno
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  3. Masaki Nagata
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  4. Masaki Tominaga
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  5. Shigehisa Aoki
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  6. Nobuko Tsuruta
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  7. Michihiro Kawashima
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  8. Shun'ichiro Taniguchi
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  9. Shin-ichiro Hayashi
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Yatsunami, J., Fukuno, Y., Nagata, M. et al. Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells. Clin Exp Metastasis 17, 359–365 (1999). https://doi.org/10.1023/A:1006605725619

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