Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease.
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.
Fenton
S L
SL
Division of Medical Sciences, University of Birmingham, UK.
Luong
Q T
QT
Sarafeim
A
A
Mustard
K J W
KJ
Pound
J
J
Desmond
J C
JC
Gordon
J
J
Drayson
M T
MT
Bunce
C M
CM
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002995:Clofibric Acid / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D018931:Antineoplastic Agents, Hormonal; C494811:BCL2L1 protein, human; D000960:Hypolipidemic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D002995:Clofibric Acid; D017258:Medroxyprogesterone Acetate