title: 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.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D020298:U937 Cells
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019319:Okadaic Acid; D006072:Gossypol; D013755:Tetradecanoylphorbol Acetate; D017239:Paclitaxel