N-(4-hydroxyphenyl)retinamide induces apoptosis in T lymphoma and T lymphoblastoid leukemia cells.
We demonstrate that N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), a synthetic retinoic acid (RA) derivative, is a potent and selective inducer of apoptosis in malignant T lymphoid cells, but has little effect on normal lymphoid cells of the thymus or spleen. 4-HPR and its stereoisomer, 9-cis-4-HPR, are 50 to > 150 times more potent than 7 other retinoids in killing CEM-C7 human T lymphoblastoid leukemia cells and P1798-C7 murine T lymphoma cells. 4-HPR's apoptotic action requires the intact molecule bearing both the retinoid moiety and the hydroxyphenol ring; 4-HPR remains unmetabolized after uptake into CEM-C7 and P1798-C7 cells for up to 24 hours. We also show that glucocorticoid (GC)-resistant variants are equally susceptible to 4-HPR as are GC-sensitive cells. Thus, 4-HPR may be potentially important as a new chemotherapeutic drug for use as alternative to, or in combination with, conventional drugs for treating lymphoid malignancies.
Chan
L N
LN
Dept. Human Biological Chemistry & Genetics, University of Texas Medical Branch at Galveston 77555-0643, USA.
Zhang
S
S
Shao
J
J
Waikel
R
R
Thompson
E A
EA
Chan
T S
TS
D000627:Aminophenols / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D017313:Fenretinide / Q000378:metabolism / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012176:Retinoids / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013237:Stereoisomerism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000627:Aminophenols; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D012176:Retinoids; D017313:Fenretinide; D014212:Tretinoin; C026729:4-aminophenol