Apoptosis induction by (+)alpha-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells.
We analyzed the effect of (+)alpha-tocopheryl succinate (alpha-TOS) alone or associated with arsenic trioxide (ATO) or all-trans retinoid acid (ATRA) in acute promyelocytic leukemia (APL). alpha-TOS-induced apoptosis in APL clinical samples and in ATRA-sensitive (NB4) and ATRA-resistant (NB4-R2) APL cell lines. The effective dose 50% (ED-50) was calculated to be 71 and 58muM, for NB4 and NB4-R2, respectively. alpha-TOS neither induced nor modified ATRA-induced differentiation of APL cells, and did not affect the proliferation and differentiation of normal CD34(+) hematopoietic progenitors in methylcellulose assays. alpha-TOS exerted a moderate antagonistic effect to ATO-induced apoptosis when treatment was done simultaneously but when alpha-TOS was added 24h after ATO, an additive effect was observed. Our results support the concept of alpha-TOS as an anti-leukemic compound which spares normal hematopoiesis.
Freitas
Rosana Aparecida
RA
Hematology Division, Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, SP, Brazil.
Silva dos Santos
Guilherme Augusto
GA
Gimenes Teixeira
Hamilton Luiz
HL
Scheucher
Priscila Santos
PS
Lucena-Araujo
Antonio Roberto
AR
Lima
Ana Sílvia Gouveia
AS
Abreu e Lima
Rodrigo Siqueira
RS
Garcia
Aglair Bergamo
AB
Jordão
Alceu Afonso
AA
Falcão
Roberto Passetto
RP
Vannucchi
Hélio
H
Rego
Eduardo Magalhães
EM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D006131:Growth Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D014212:Tretinoin; D024502:alpha-Tocopherol; D000077237:Arsenic Trioxide