Cancer Immunology, Immunotherapy

, Volume 31, Issue 6, pp 358–364 | Cite as

Regression mechanisms of mouse fibrosarcoma cells after in vitro exposure to quercetin: Diminution of tumorigenicity with a corresponding decrease in the production of prostaglandin E2

  • Futoshi Okada
  • Masuo Hosokawa
  • Junji Hasegawa
  • Makoto Ishikawa
  • Itsuo Chiba
  • Yayoi Nakamura
  • Hiroshi Kobayashi
Original articles


We have previously reported that both regressor (QR) and progressor (metastatic, QP) clones were obtained after the in vitro exposure of a mouse fibrosarcoma BMT-11 cl-9 to quercetin [17]. In this study, we investigated possible mechanisms of spontaneous regression of QR clones as compared with tumorigenic QP and BMT-11 cl-9 tumor clones. We observed that BMT-11 cl-9 cells produced relatively high amounts of prostaglandin E2 (PGE2) during in vitro culture. The average production by 11 subclones of BMT-11 cl-9 cells was 9236±2829 pg/ml whereas that by 9 QR clones was 3411±2213 pg/ml (P <0.02). Indomethacin not only inhibited in vitro PGE2 synthesis by QP clones (high-PGE2 producers) but also the s.c. growth of QP clones in mice. Chronological changes in host immune responses to tumor-associated antigen were measured by cytotoxic T lymphocyte (CTL) activity examined after mixed lymphocyte/tumor cell culture of spleen cells obtained from tumor-bearing mice. The CTL activity disappeared abruptly in the spleen of QP-clonebearing mice 21 days after the inoculation of tumors, whereas the spleen cells of QR-clone-inoculated mice retained their CTL activity. We determined that the mechanism responsible for the regression of these regressor clones is not due to any qualitative or quantitative increase in pre-existing membrane antigens, nor the emergence of new antigen(s) on the cell surface of the QR clones; nor was it due to enhanced susceptibility of QR clones to natural killer cells, lymphokine-activated killer cells and macrophages. These finding suggest that the regression mechanism of QR clones may be the diminished inhibition of host response to tumor-associated antigen caused by the reduced production of PGE2 by QR clones.


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Futoshi Okada
    • 1
  • Masuo Hosokawa
    • 1
  • Junji Hasegawa
    • 1
  • Makoto Ishikawa
    • 1
  • Itsuo Chiba
    • 1
  • Yayoi Nakamura
    • 1
  • Hiroshi Kobayashi
    • 1
  1. 1.Laboratory of Pathology, Cancer InstituteHokkaido University School of MedicineSapporoJapan

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