Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease

被引:18
作者
Fenton, SL
Luong, QT
Sarafeim, A
Mustard, KJW
Pound, J
Desmond, JC
Gordon, J
Drayson, MT
Bunce, CM [1 ]
机构
[1] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England
[2] Univ Birmingham, Div Med Sci, Birmingham B15 2TT, W Midlands, England
基金
英国医学研究理事会;
关键词
apoptosis; fibrates; medroxyprogesterone acetate; Burkitt's lymphoma; combination therapy;
D O I
10.1038/sj.leu.2402843
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Current therapies for Burkitt's lymphoma (BL) utilise combined cytotoxic chemotherapy, but these treatments are not always available in areas where the disease is endemic and are also markedly less successful in AIDS-related BL. Therefore, additional therapies are urgently required. We demonstrate here that combined fibrates and MPA exert powerful, antiproliferative actions against well-characterised Daudi, Raji and L3055 BL cell lines and primary BL cells. Detailed studies in L3055 demonstrated that this activity was mediated by induced apoptosis and confirmed by observations that overexpression of the antiapoptotic genes bcl-2 or bcl-X-L conferred significant protection against the drugs. Importantly, since fibrates and MPA are inexpensive and stable with minimal-associated toxicities, we suggest that these drugs should be considered as adjuncts to currently available treatments for BL in endemic and AIDS-related disease.
引用
收藏
页码:568 / 575
页数:8
相关论文
共 51 条
[1]  
[Anonymous], BR MED J
[2]   Dissociative glucocorticoid activity of medroxyprogesterone acetate in normal human lymphocytes [J].
Bamberger, CM ;
Else, T ;
Bamberger, AM ;
Beil, FU ;
Schulte, HM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (11) :4055-4061
[3]   CHOD/BVAM regimen plus radiotherapy in patients with primary CNS non-Hodgkin's lymphoma [J].
Bessell, EM ;
Graus, F ;
López-Guillermo, A ;
Villá, S ;
Verger, E ;
Petit, J ;
Holland, I ;
Byrne, P .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 50 (02) :457-464
[4]   BURKITTS-LYMPHOMA - A MODEL FOR CLINICAL ONCOLOGY [J].
BOUFFET, E ;
FRAPPAZ, D ;
PINKERTON, R ;
FAVROT, M ;
PHILIP, T .
EUROPEAN JOURNAL OF CANCER, 1991, 27 (04) :504-509
[5]   Acquired immunodeficiency syndrome-related systemic non-Hodgkin's lymphoma [J].
Bower, M .
BRITISH JOURNAL OF HAEMATOLOGY, 2001, 112 (04) :863-873
[6]  
Breen EC, 1999, CLIN IMMUNOL, V92, P293
[7]   Potentiation of myeloid differentiation by anti-inflammatory agents, by steroids and by retinoic acid involves a single intracellular target, probably an enzyme of the aldoketoreductase family [J].
Bunce, CM ;
Mountford, JC ;
French, PJ ;
Mole, DJ ;
Durham, J ;
Michell, RH ;
Brown, G .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1996, 1311 (03) :189-198
[8]  
Cariati R, 2000, INT J CANCER, V86, P375, DOI 10.1002/(SICI)1097-0215(20000501)86:3<375::AID-IJC12>3.0.CO
[9]  
2-Z
[10]   Palliation of AIDS-related primary lymphoma of the brain: Observations from a multi-institutional database [J].
Corn, BW ;
Donahue, BR ;
Rosenstock, JG ;
Cooper, JS ;
Xie, Y ;
Brandon, AH ;
Hegde, HH ;
Sherr, DL ;
Fisher, SA ;
Berson, A ;
Han, HK ;
Wahab, MA ;
Koprowski, CD ;
Ruffer, JE ;
Curran, WJ .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1997, 38 (03) :601-605