Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells

被引:64
作者
Dörrie, J [1 ]
Sapala, K [1 ]
Zunino, SJ [1 ]
机构
[1] Univ Erlangen Nurnberg, Chair Genet, D-91058 Erlangen, Germany
关键词
B-lineage leukemia; acute lymphoblastic leukemia; Bcl-2; apoptosis; carnosol;
D O I
10.1016/S0304-3835(01)00549-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Carnosol, a phenolic compound extracted from the herb rosemary has been reported to have anti-cancer activity. We investigated whether carnosol was cytotoxic against several pro-B and pre-B acute lymphoblastic leukemia (ALL) lines. In all ALL lines tested, carnosol induced apoptotic cell death distinguished by loss of nuclear DNA, externalization of cell membrane phosphatidylserine, and depolarization of mitochondrial membranes. Flow cytometric measurement of Bcl-2 protein levels revealed that carnosol induced a 34-53% decrease in Bcl-2 in the cell population exhibiting a viable phenotype prior to detectable apoptotic changes in morphology. These results suggest that carnosol may be useful as a novel chemotherapeutic agent against B-lineage leukemias, and possibly other types of cancers that express high levels of the protective protein, Bcl-2. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:33 / 39
页数:7
相关论文
共 18 条
[1]   BCL-2 FAMILY: Regulators of cell death [J].
Chao, DT ;
Korsmeyer, SJ .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :395-419
[2]   MITOCHONDRIAL MODIFICATIONS DURING RAT THYMOCYTE APOPTOSIS - A STUDY AT THE SINGLE-CELL LEVEL [J].
COSSARIZZA, A ;
KALASHNIKOVA, G ;
GRASSILLI, E ;
CHIAPPELLI, F ;
SALVIOLI, S ;
CAPRI, M ;
BARBIERI, D ;
TROIANO, L ;
MONTI, D ;
FRANCESCHI, C .
EXPERIMENTAL CELL RESEARCH, 1994, 214 (01) :323-330
[3]   Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia [J].
CoustanSmith, E ;
Kitanaka, A ;
Pui, CH ;
McNinch, L ;
Evans, WE ;
Raimondi, SC ;
Behm, FG ;
Arico, M ;
Campana, D .
BLOOD, 1996, 87 (03) :1140-1146
[4]   FEATURES OF APOPTOTIC CELLS MEASURED BY FLOW-CYTOMETRY [J].
DARZYNKIEWICZ, Z ;
BRUNO, S ;
DELBINO, G ;
GORCZYCA, W ;
HOTZ, MA ;
LASSOTA, P ;
TRAGANOS, F .
CYTOMETRY, 1992, 13 (08) :795-808
[5]   ANALYSIS AND DISCRIMINATION OF NECROSIS AND APOPTOSIS (PROGRAMMED CELL-DEATH) BY MULTIPARAMETER FLOW-CYTOMETRY [J].
DIVE, C ;
GREGORY, CD ;
PHIPPS, DJ ;
EVANS, DL ;
MILNER, AE ;
WYLLIE, AH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1133 (03) :275-285
[6]   Regulation of CD95 expression and CD95-mediated cell death by interferon-γ in acute lymphoblastic leukemia with chromosomal translocation t(4;11) [J].
Dörrie, J ;
Schuh, W ;
Keil, A ;
Bongards, E ;
Greil, J ;
Fey, GH ;
Zunino, SJ .
LEUKEMIA, 1999, 13 (10) :1539-1547
[7]   Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia [J].
Faderl, S ;
Kantarjian, HM ;
Talpaz, M ;
Estrov, Z .
BLOOD, 1998, 91 (11) :3995-4019
[8]   THE ACUTE LYMPHOBLASTIC-LEUKEMIA CELL-LINE SEM WITH T(411) CHROMOSOMAL REARRANGEMENT IS BIPHENOTYPIC AND RESPONSIVE TO INTERLEUKIN-7 [J].
GREIL, J ;
GRAMATZKI, M ;
BURGER, R ;
MARSCHALEK, R ;
PELTNER, M ;
TRAUTMANN, U ;
HANSENHAGGE, TE ;
BARTRAM, CR ;
FEY, GH .
BRITISH JOURNAL OF HAEMATOLOGY, 1994, 86 (02) :275-283
[9]  
HUANG MT, 1994, CANCER RES, V54, P701
[10]  
LANGE B, 1987, BLOOD, V70, P192