The arotinoid Ro 40-8757 has antiproliferative effects in drug-resistant human colon and breast cancer cell lines in vitro.
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-7mdr1. 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 (IC50) in drug-resistant and parental cell lines (range, 0.06 x 10(-6) to 0.57 x 10(-6) M). We conclude that: (1) thymidylate synthase is not involved in the mechanism of action of Ro 40-8757; (2) the mdr1 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.
Louvet
C
C
INSERM U55, Hôpital Saint-Antoine, Paris, France.
Empereur
S
S
Fagot
D
D
Forgue-Lafitte
E
E
Chastre
E
E
Zimber
A
A
Mester
J
J
Gespach
C
C
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009025:Morpholines; D012176:Retinoids; D004317:Doxorubicin; C081137:mofarotene; D005472:Fluorouracil