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 inducti on of either necrosis or apoptosis by eicosapentaenoic acid (EPA) in the ly mphoma cell lines Raji and Ramos, respectively. To investigate the differen t death modes induced by EPA, we assessed the importance of some antioxidan ts and reactive oxygen species in the two cell lines. We observed that diff erent antioxidants counteracted the necrotic effect bf EPA on Raji cells to a different extent, and that vitamin E counteracted EPA-induced accumulati on of superoxide anion in this cell line. On the contrary, no effects of an tioxidants were observed on development of apoptosis induced by EPA in Ramo s cells, and Vitamin E did not counteract EPA-induced accumulation of super oxide anions in Ramos cells. Moreover, apoptosis was partly inhibited by tr anscription inhibitors (actinomycin D) and protein synthesis inhibitors (cy cloheximide), suggesting dependency upon new protein synthesis prior to apo ptosis. Kinase inhibitors (staurosporin and calphostin C) did not alter the EPA-induced apoptosis. The observed cellular accumulation of superoxide an ion following EPA incubation may be important for induction of necrosis in Raji cells. In contrast, none of the other investigated parameters indicate d a role of oxidative stress promoted by EPA in the induction of apoptosis in Ramos cells.