Cytotoxic effects of vitamin A in combination with vincristine, daunorubicin and 6-thioguanine upon cells from lymphoblastic leukemic patients.
We studied whether isotretinoin potentiated the effects of vincristine (VCR), daunorubicin (DNR), and 6-thioguanine (6-TG) against cells obtained from 24 patients with acute lymphoblastic leukemia (ALL). Treatment with 5 micrograms/ml isotretinoin alone resulted in a leukemic cell survival of 82% +/- 28.1%. So isotretinoin is toxic to ALL cells. Dose-response curves were obtained for VCR, DNR and 6-TG in the presence and absence of isotretinoin Isotretinoin showed additive leukemic cell kills in combination with VCR and DNR. When corrected for cell kill by isotretinoin alone, it appeared that isotretinoin did not significantly enhance leukemic cell kills by VCR, DNR and 6-TG. No differences were found between samples from patients at initial diagnosis and at relapse with respect to cell kill by isotretinoin alone and with respect to a possible synergistic effect of isotretinoin and the cytostatic drugs. It is concluded that isotretinoin has additive antileukemic effects in combination with VCR or DNR. However, isotretinoin does not potentiate the antileukemic effects of VCR, DNR and 6-TG against leukemic cells obtained from patients with ALL.
Free University Hospital, Department of Pediatrics, Amsterdam, The Netherlands.
R
R
Pieters
D R
DR
Huismans
A H
AH
Loonen
K
K
Hählen
A J
AJ
Veerman
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D013866:Thioguanine / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage; D014801:Vitamin A / Q000494:pharmacology*
D014801:Vitamin A; D014750:Vincristine; D015474:Isotretinoin; D013866:Thioguanine; D003630:Daunorubicin