RESUMO
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.
Assuntos
Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Linfoma de Burkitt/patologia , Ácido Clofíbrico/farmacologia , Hipolipemiantes/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Linfoma de Burkitt/tratamento farmacológico , Divisão Celular/efeitos dos fármacos , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Transdução Genética , Células Tumorais Cultivadas , Proteína bcl-XRESUMO
Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated by patients. We demonstrate that clofibric acid (CA) enhances the response of HL60 cells to all-trans RA and D3. Our findings and those of others in the field lead us to suggest that combination therapy using all-trans RA and CA should be considered as potential therapy for AML and MDS.