Skip to main content
Log in

Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice

  • Research Articles
  • Articles
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Azuma, I., Kishimoto, S., Yamamura, Y., and Petit, J.F., Adjuvanticity of mycobacterial cell walls.Jpn. J. Microbiol., 15, 193–197 (1971).

    PubMed  CAS  Google Scholar 

  • Azuma, I., Ribi, E.E., Meyer, T.J., and Zber, B., Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3.J. Natl. Cancer Inst., 52, 95–101 (1974).

    PubMed  CAS  Google Scholar 

  • Azuma, I. and Yamamura, Y., Immunotherapy of cancer with BCG cell-wall skeleton and related materials.Gann Monogr. Cancer Res., 24, 121–141 (1979).

    CAS  Google Scholar 

  • Bingham, E., Stemmer, K.L., and Falk, H.L., The effects of repeated injections of certain adjuvants on chemical carcinogenesis.Ann. Allergy, 25, 684–690 (1967).

    PubMed  CAS  Google Scholar 

  • Fidler, I.J., Selection of successive tumour lines for metastasis.Nat. New Biol., 242, 148–149 (1973).

    PubMed  CAS  Google Scholar 

  • Freund, J., The mode of action of immunological adjuvants.Adv. Tuberc. Res., 7, 130–148 (1956).

    Google Scholar 

  • Han, M.J., Park, H.Y., and Kim, D.H., Pretective effects ofBifidobacterium spp. on experimental colon carcinigenesis with 1,2-dimethylhydrazine.J. Microbiol. Biotechnol., 9, 368–370 (1999).

    CAS  Google Scholar 

  • Hayashi, A., Interferon-g as a marker for the effective cancer immunotherapy with BCG-cell wall skeleton.Proc. Japan Acad., 70, 205–209 (1994).

    Article  CAS  Google Scholar 

  • Hayashi, A., and Noda, A., Does the cell wall skeleton from Bacille Calmette-Guerin directly induce interferon-g, independent of interleukin-12?Jpn. J. Clin. Oncol., 26, 124–127 (1996).

    PubMed  CAS  Google Scholar 

  • Hirao, F., Nishikawa, H., Yasaki, S., Ogura, T., Azuma, I., Taniyama, T., Yoshimoto, T., Kishimoto, S., and Yamamura, Y., Effect of oil-attached BCG cell-wall skeleton and thymectomy on the incidence of lung cancer and amyloidosis induced by chemical carcinogens in rabbits.Gann, 69, 453–459 (1978).

    PubMed  CAS  Google Scholar 

  • Kang, T.Y., Park, S.H., and Choe, T.B., Immunostimulating effects of cell wall components isolated fromLactobacillus plantarum.J. Microbiol. Biotechnol., 4, 195–199 (1994).

    CAS  Google Scholar 

  • Kuwamura, S., Studies on the relationship between the induction of primary hepatic carcinoma by 3′-methyl-4-dimethylaminoazobenzene and cell-mediated immunity in hosts.J. Osaka City Med. Cent., 26, 145–157 (1977).

    CAS  Google Scholar 

  • Matsumoto, M., Seya, T., Kikkawa, S., Tsuji, S., Shida, K., Nomura, M., Kurita-Taniguchi, M., Ohigashi H., Yokouchi, H., Takami, H., Hayashi, A., Azuma, I., Masaoka, T., Kodama, K., and Toyoshima, K., Interferon gamma-producing activity in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton.Int. Immunopharmacol., 1(8), 1559–1569 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Ogura, T., Namba, M., Hirao, F., Yamawaki, M., Azuma, I., and Yamamura Y., Effect of BCG cell-wall skeleton on metastasis of syngeneic tumor in rats, with special reference to lymphocyte trapping.Gann, 69, 311–315 (1978).

    PubMed  CAS  Google Scholar 

  • Okuyama, H. and Morikawa, K., Histological study on adjuvanticity of BCG-cell wall: Comparison of adjuvanticity between oil-in-water and water-in-oil forms.GANN Monogr. Cancer Res., 21, 87–91 (1978).

    Google Scholar 

  • Tokuzen, R., Okabe, M., Nakahara, W., Azuma, I., and Yamamura, Y., Effect of Nocardia and Mycobacterium cell-wall skeletons on autochthonous tumor grafts.Gann, 66, 433–435 (1975).

    PubMed  CAS  Google Scholar 

  • Whitehouse, M.W., Orr, K.J., Beck, F.W., and Pearson, C., Freund’s Adjuvants: Relationship of arthritogenicity and adjuvanticity in rats to vehicle composition.Immunology, 27, 311–330 (1974).

    PubMed  CAS  Google Scholar 

  • Yoo, Y.C., Saiki, I., Sato, K., and Azuma, I., MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the metastasis of haematogenous and non-haematogenous tumors in mice.Vaccine, 12, 175–180 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Yoo, Y.C., Watanabe, S., Watanabe, R., Hata, K., Shimazaki, K., and Azuma, I., Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice.Jpn. J. Cancer Res., 88, 184–19 (1997).

    PubMed  CAS  Google Scholar 

  • Yoo, Y.C., Park, S.Y., Lee, K.B., and Azuma, I., MDP-Lys(L18), a synthetic muramyl dipeptide derivative, enhances antitumor activity of an inactivated tumor vaccine.J. Microbiol. Biotechnol., 10, 399–404 (2000).

    CAS  Google Scholar 

  • Yoshimoto, T., Azuma, I., Sakatani, M., Nishikawa, H., Ogura, T., Hirao, F., and Yamamura, Y., Effect of oil-attached BCG cell-wall skeleton on the induction of pleural fibrosarcoma in mice.Gann, 67, 441–445 (1976).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yung Choon Yoo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoo, Y.C., Hata, K., Lee, K.B. et al. Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice. Arch Pharm Res 25, 522–527 (2002). https://doi.org/10.1007/BF02976612

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02976612

Key words

Navigation