RESUMO
Targeting the nuclear factor kappa B (NFκB) pathway is proposed as therapy for chronic lymphocytic leukemia (CLL). We hypothesized that an omega-3 fatty acids (n-3) supplement would suppress NFκB activation in lymphocytes of Rai Stage 0-1 CLL patients. The initial dose of 2.4 g n-3/day was gradually increased to 7.2 g n-3/day. After n-3 consumption: 1) plasma n-3 increased; 2) NFκB activation was suppressed in lymphocytes; 3) in vitro sensitivity of lymphocytes to doxorubicin was increased; and 4) expression of 32 genes in lymphocytes was significantly decreased.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Linfócitos/metabolismo , NF-kappa B/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Suplementos Nutricionais , Doxorrubicina/uso terapêutico , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/sangue , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of RBCs might accurately indicate incorporation of omega 3 fatty acids in the WBCs. In this report we determine and compare the changes in fatty acid compositions of red blood cells and white blood cells in response to consumption of three doses of an omega 3 fatty acid supplement. RESULTS: We found that the fraction of omega 3 fatty acids in both red blood cells and white blood cells increased following consumption of the supplement. There was a linear, dose responsive increase in the fraction of omega 3 fatty acids in red blood cells but the increase in omega 3 in white blood cells was not linear. The magnitude of increase in omega 3 fatty acids was different between the two cell types. CONCLUSIONS: Fatty acid analysis of red blood cells is a good measure of compliance with supplement consumption. However, fatty acid analysis of white blood cells is needed to correlate changes in fatty acid composition of white blood cells with other biochemical changes in the white blood cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00899353.
