Necrosis and apoptosis in lymphoma cell lines exposed to eicosapentaenoic acid and antioxidants.
The present study is focused on the role of oxidative stress in the induction of either necrosis or apoptosis by eicosapentaenoic acid (EPA) in the lymphoma cell lines Raji and Ramos, respectively. To investigate the different death modes induced by EPA, we assessed the importance of some antioxidants and reactive oxygen species in the two cell lines. We observed that different antioxidants counteracted the necrotic effect of EPA on Raji cells to a different extent, and that vitamin E counteracted EPA-induced accumulation of superoxide anion in this cell line. On the contrary, no effects of antioxidants were observed on development of apoptosis induced by EPA in Ramos cells, and vitamin E did not counteract EPA-induced accumulation of superoxide anions in Ramos cells. Moreover, apoptosis was partly inhibited by transcription inhibitors (actinomycin D) and protein synthesis inhibitors (cycloheximide), suggesting dependency upon new protein synthesis prior to apoptosis. Kinase inhibitors (staurosporin and calphostin C) did not alter the EPA-induced apoptosis. The observed cellular accumulation of superoxide anion following EPA incubation may be important for induction of necrosis in Raji cells. In contrast, none of the other investigated parameters indicated a role of oxidative stress promoted by EPA in the induction of apoptosis in Ramos cells.
Heimli
H
H
Institute for Nutrition Research, University of Oslo, Norway.
Finstad
H S
HS
Drevon
C A
CA
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology*; D009281:Naphthalenes / Q000494:pharmacology; D009336:Necrosis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011500:Protein Synthesis Inhibitors; D013481:Superoxides; D014810:Vitamin E; D015118:Eicosapentaenoic Acid; D005979:Glutathione Peroxidase; D011493:Protein Kinase C; C058819:calphostin C