Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis.
The transcription factor nuclear factor kappaB (NFkappaB) 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 NFkappaB in cancer therapyusing a transgenic approach in mice. We found that NFkappaB 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 NFkappaB inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NFkappaB inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis.
Scaife
Courtney L
CL
Department of Surgery, Salt Lake City Veterans Administration Medical Center, and University of Utah, Salt Lake City, Utah 84132, USA.
Kuang
Jinqiu
J
Wills
Jason C
JC
Trowbridge
D Brad
DB
Gray
Phil
P
Manning
Bernadette M
BM
Eichwald
Ernst J
EJ
Daynes
Raymond A
RA
Kuwada
Scott K
SK
D000008:Abdominal Neoplasms / Q000556:secondary; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009366:Neoplasm Seeding; D009368:Neoplasm Transplantation; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; C416282:BAY 11-7085; D016328:NF-kappa B; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones