The arotinoid Ro 40-8757 has antiproliferative effects in drug-resistant human colon and breast cancer cell lines in vitro

Abstract We have examined the antiproliferative effects of the arotinoid Ro 40-8757 in 3 drug-resistant human adenocarcinoma cell lines: the colonic cells HT29-5FU and CaCo2, and the mammary cells MCF-7mdrl. Whereas all- trans retinoic acid had no effect at the concentration of 10 −6 M, Ro 40-8757 was found to exert a high antiproliferative action with similar inhibitory potency (IC 50 ) in drug-resistant and parental cell lines (range, 0.06 × 10 −6 to 0.57 × 10 −6 M). We conclude that: (1) thymidylate synthase is not involved in the mechanism of action of Ro 40-8757; (2) the mdrl gene product does not recognize this retinoic derivative; and (3) Ro 40-8757, alone or in combinations with other cytotoxic drugs, can be very useful in patients with progressive disease after conventional chemotherapy.