Z-100, an immunomodulatory extract of Mycobacterium tuberculosis Strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma

Takayuki Horii, Koji Yoshinaga, Nobuyoshi Kobayashi, Koichi Seto, Yuki Orikawa, Masahiro Okamoto, Runa Eta, Yuta Ohira, Kokichi Katsunuma, Yuko Hori, Takao Tanaka, Mineo Takei

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Abstract

Lymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan. Here, we investigated the inhibitory effect of Z-100 on spontaneous lymphatic metastasis. C57BL/6N mice injected subcutaneously with B16-BL6 melanoma cells in the right hind footpad were administered Z-100 subcutaneously in the right inguinal region on a daily basis. On day twenty-one after the injection, the right inguinal lymph nodes were excised, and the extent of metastasis, the number of immune cells, and the amount of granzyme B protein in the lymph nodes were examined. We also investigated the combined effect of Z-100 and irradiation in this model. Results showed that Z-100 reduced number of animals with metastasis, with respective metastasis rates of 85.7%, 42.9%, 7.1% and 0.0% in saline, 0.1 mg/kg Z-100, 1 mg/kg Z-100 and 10 mg/kg Z-100 group. Further, mice that had been given Z-100 were found to have more immune cells and granzyme B protein in the lymph nodes than control mice. The combination of low dose Z-100 and irradiation also inhibited spontaneous lymph node metastases. These findings suggest that Z-100 may be beneficial in preventing lymphatic metastasis by enhancing the immune response.

Original languageEnglish
Pages (from-to)642-647
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume37
Issue number4
DOIs
Publication statusPublished - 04-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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    Horii, T., Yoshinaga, K., Kobayashi, N., Seto, K., Orikawa, Y., Okamoto, M., Eta, R., Ohira, Y., Katsunuma, K., Hori, Y., Tanaka, T., & Takei, M. (2014). Z-100, an immunomodulatory extract of Mycobacterium tuberculosis Strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma. Biological and Pharmaceutical Bulletin, 37(4), 642-647. https://doi.org/10.1248/bpb.b13-00927