Nuclear Transcription Factor Kappa B Downregulation Reduces Chemoresistance in Bone Marrow-derived Cells Through P-glycoprotein Modulation

Inhibition of the NF-κB pathway increases the susceptibility of bone marrow-derived cells to anticancer drugs that is mediated by P-glycoprotein activity. (A) Canonical NF-κB signaling. (B) Pharmacological and genetic inhibition of NF-κB signaling 1. Bay 11-7085 inhibits the phosphorylation of I kappa B α by IKK (IκB kinase), which blocks the proteasomal degradation of the inhibitor protein I kappa B α, allowing the sequestration of NF-κB B in the cytoplasm. 2. Adenovirus IκB α mutant encodes an IκB α protein that cannot be phosphorylated by IKK due to mutations in serine residues 32 and 36.112