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[Cancer Research 62, 6870-6878, December 1, 2002]
© 2002 American Association for Cancer Research

Experimental Therapeutics

Nuclear Factor {kappa}B Inhibitors Induce Adhesion-dependent Colon Cancer Apoptosis

Implications for Metastasis1

Courtney L. Scaife2, Jinqiu Kuang, Jason C. Wills, D. Brad Trowbridge, Phil Gray, Bernadette M. Manning, Ernst J. Eichwald, Raymond A. Daynes and Scott K. Kuwada3

Departments of Medicine [J. K., J. C. W., D. B. T., P. G., S. K. K.], Surgery [C. L. S.], and Pathology [B. M. M., E. J. E., R. A. D.], Salt Lake City Veterans Administration Medical Center, and University of Utah, Salt Lake City, Utah 84132

The transcription factor nuclear factor {kappa}B (NF{kappa}B) is constitutively active in many types of cancercells and regulates the expression of several antiapoptotic genes. Previous studies demonstrated a role for the inhibition of NF{kappa}B in cancer therapyusing a transgenic approach in mice. We found that NF{kappa}B was transiently activated much greater than background constitutive levels during colon cancer cell readhesion, which rendered the readhering colon cancer cells exquisitely susceptible to apoptosis in the presence of soluble NF{kappa}B inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NF{kappa}B inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis.




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