Function of retinoid acid receptor alpha and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis.
All-trans-retinoic acid (ATRA) is a morphogenetic signalling molecule derived from vitamin A and is used clinically to target acute promyelocytic leukemia by inducing differentiation of immature blood cells. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Retinoic acid receptors consist of RARalpha, RARbeta and RARgamma isotypes. Among these components, RARalpha is preferentially bound to ATRA, which is used to treat acute T-lymphoblastic leukemia, yet the conditions and mechanisms remain unknown. In this study, we have demonstrated that, in human acute T-lymphoblastic leukemia Molt3 cells, inhibition of RA-induced proliferation results from massive cell death characterised by apoptosis. The effect of ATRA:RARalpha binding on apoptosis in Molt3 cells has been investigated. Consequently, it has been shown that, in RA-treated Molt3 cells, upregulation of p21 due to RA accompanies caspase 3/PARP activation which precedes the occurrence of apoptosis.
Luo
Peihua
P
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Lin
Meili
M
Lin
Meihua
M
Chen
Yiyu
Y
Yang
Bo
B
He
Qiaojun
Q
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology*; D003720:Densitometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases