ANTIPROLIFERATIVE EFFECTS OF THE AROTINOID RO-40-8757 ON HUMAN CANCERCELL-LINES INVITRO

A novel arotinoid with a morpholine structure in the polar end group R o 40-8757 hyl-2-naphthyl)propenyl]phenoxy]ethyl]-morpholine) was teste d for its anti-proliferative activity against nine human cancer cell l ines in vitro. The lines included two estrogen receptor positive breas t cancer lines (MCF-7 and' ZR-75-1), two estrogen receptor negative br east cancer lines (MDA-MB-231 and BT-20), one cervix carcinoma line (K B-3-1), two lung adenocarcinoma lines (A549 and HLC-1), one large cell lung cancer line (LXFL 529) and two colorectal lines (CXF 243 and CXF 280). Proliferation of all the lines, except the two lung adenocarcin oma lines, was inhibited by lower concentrations of Ro 40-8757 than th ose of all-trans retinoic acid (RA) or 13-cis RA giving the same level of inhibition. The degree of inhibition of RO 40-8757 was concentrati on and time dependent. The arotinoid was not cytotoxic and morphologic al signs by differentiation were not evident in cultures treated with Ro 40-8757 for up to 2 weeks. Because this compound is active on cells such as KB-3-1 that are not inhibited by all-trans RA and because it does not bind to nuclear retinoic acid receptors, it may represent a n ovel class of anti-proliferative agents.