Nuclear Factor κB Inhibitors Induce Adhesion-dependent Colon Cancer Apoptosis: Implications for Metastasis

The transcription factor nuclear factor κB (NFκB) 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 NFκB in cancer therapyusing a transgenic approach in mice. We found that NFκB 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 NFκB inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NFκB inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis.