ro-15-1570 and Colorectal-Neoplasms

Human colorectal tumor cells expressing differing metastatic potential and tissue transglutaminase (TGA) activity were tested for the ability of various pharmacological agents to enhance TGA activity. The most effective stimulant was tetradecanoylphorbol-13-acetate (TPA), which in human colon carcinoma cells (SW620) caused a 5-fold, protein synthesis dependent increase in activity over 3 days. In WiDr and SW480 cells TGA activity was less susceptible to induction by TPA, possibly owing to the higher basal levels of TGA. Retinoic acid and a synthetic retinoid, [RO 15-1570; (E)-4-[2(5,6,7,8-tetramethylnaphthalene-2-yl)propen-1-yl] benzenesulphonyl-ethane)], also induced TGA activity to a lesser extent in SW620 cells, whereas other differentiation inducers [sodium butyrate and hexamethylene bis-acetamide (HMBA)] were ineffective. In LS174T cells, TGA activity was resistant to induction by all of the agents. The synthetic retinoid (RO 15-1570) inhibited in vitro invasiveness of SW620 cells, however, TPA treatment or addition of exogenous TGA did not inhibit invasiveness of these cells. Hence, the invasive behavior of a metastatic human colon tumor cell line (SW620) does not appear to be dependent on the TGA activity which the cells express. The anti-invasive activity of the retinoid in SW620 cells therefore may be mediated by some other mechanism.

Topics: Adenocarcinoma; Colonic Neoplasms; Colorectal Neoplasms; Humans; Neoplasm Invasiveness; Retinoids; Tetradecanoylphorbol Acetate; Transglutaminases; Tretinoin; Tumor Cells, Cultured