Gossypol decreases tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression via suppression of NF-κB activity

Abstract

Gossypol is a yellowish polyphenolic compound originally from cotton plant, which has been shown to exert a potential for anti-cancer and anti-inflammatory effects. However, its molecular mechanism is not thoroughly understood on breast cancer cells known to highly express intercellular adhesion molecule-1 (ICAM-1) for their adhesion and metastasis. This study aims to investigate the effect of gossypol on tumor necrosis factor (TNF)-α-stimulated ICAM-1 via nuclear factor-kappa B (NF-κB) activity. Gossypol was shown to inhibit TNF-α-induced ICAM-1 expression and U937 cell adhesion to MDA-MB-231 and MCF-7 cells. Additionally, TNF-α-induced MDA-MB-231 cell invasion was blocked in the presence of gossypol. Chromatin immunoprecipitation analysis demonstrated that gossypol blocks NF-κB binding on the ICAM-1 promoter regions. Additionally, TNF-α-induced NF-κB activation was completely suppressed in the presence of gossypol. Gossypol did not directly suppress the binding of NF-κB to the DNA but rather inhibited the nuclear translocation of p65 and p50 via phosphorylation and degradation of IκB. We also found that gossypol suppresses NF-κB activation induced by a wide variety of agents, including taxol, okadaic acid, and phorbol myristate acetate. Taken together, gossypol effectively inhibited TNF-α-induced ICAM-1 expression via the suppression of NF-κB activation and in vitro adhesion and invasion in human breast cancer cells.