Retinol tends to reduce activator protein‐1 and nuclear factor kappa B mediated gene transcription in cultured human colorectal cancer cells

Abstract

Retinol decreases matrixmetalloproteinase 9 (MMP‐9) mRNA in colon cancer cells. The MMP‐9 promoter contains activator protein‐1 (AP‐1) and nuclear factor kappa B (NFkB) responsive elements. Our objective was to determine if retinol could affect AP‐1 and NFkB mediated gene expression. Luciferase reporter constructs containing AP‐1 or NFkB responsive elements were transfected into HCT‐116 colon cancer cells. Cells transfected with the AP‐1 construct received 20 ng/ml phorbol myristate acetate (PMA), 10 microM retinol, PMA and retinol, or vehicle (control) for 24 h. Cells transfected with the NFkB construct received 20 ng/ml tumor necrosis factor alpha (TNFalpha), 10 microM retinol, TNFalpha and retinol, or vehicle for 24 h. Treatment of cells containing the AP‐1 reporter with PMA increased luciferase activity to 280 ± 79% control. Treatment with PMA and retinol tended to reduce luciferase activity to 164 ± 39% control (P = 0.16). Treatment of cells transfected with the NFkB reporter with TNFalpha increased luciferase activity to 418 ± 142% control; while TNFalpha and retinol tended to decrease luciferase activity to 227 ± 121% control (P = 0.13). In summary, retinol tends to reduce gene transcription via AP‐1 and NFkB responsive elements. This may account, at least in part, for the ability of retinol to decrease MMP‐9 mRNA.This research was sponsored by a grant from the American Institute for Cancer Research to ML.