A retinoic acid resistant HL-60 cell clone sensitive to N-(4-hydroxyphenyl) retinamide-mediated clonal growth inhibition.
Among the Retinoic Acid (RA) derivatives, retinamides, and in particular N-(4-hydroxyphenyl) retinamide (4-HPR), are currently being investigated in selected cases of cancer chemoprevention. The cellular target range, however, seems to be limited, as cells of hemopoietic origin are virtually incapable of terminal differentiation upon addition of the compound. We have reconsidered the effect of 4-HPR on HL-60 cells by taking advantage of a mutant clone, generated in our laboratory, unresponsive to RA but highly responsive to dimethylsulfoxide (DMSO). We show here that this clone, upon addition of 4-HPR, although unable of undergoing full differentiation, shows considerable reduction of clonal growth. Moreover, the combination of 4-HPR and RA resulted in a much greater effect than the administration of 4-HPR alone. We suggest that 4-HPR and RA, at least in terms of mediating growth inhibition, may follow different metabolic pathways.
Brigati
C
C
Molecular Biology Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Ferrari
N
N
Megna
M
M
Roncella
S
S
Cutrona
G
G
Tosetti
F
F
Vidali
G
G
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D017313:Fenretinide / Q000494:pharmacology*; D005434:Flow Cytometry; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017313:Fenretinide; D014212:Tretinoin; D004121:Dimethyl Sulfoxide