抄録
Epidemiological studies of breast and pancreatic cancer in several Mediterranean countries, including Southern Europe, North Africa, and the Middle East have demonstrated that increased dietary intake of oleic acid may reduce a risk of cancer onset. It is well-known that eicosapentaenoic acid (EPA), which is one of the PUFAs, was demonstrated to inhibit proliferation of human leukemic HL-60 cells in vitro. We studied the mechanism of apoptosis in HeLa cells by oleic acids as compared with those by EPA, which was previously reported to induces apoptosis. In this study, we found that the fragmentation of DNA was detected in agarose electrophoresis and apoptotic features, such as cell shrinkage, concentration, and fragmentation of nucleus after addition by 100μM of oleic acids and EPA. After 24 hours of medication by EPA and oleic acid, the apoptosis-related proteins (Bax, Bcl-2, Fas, cytochrome C, Apaf-1, caspase 3) were analyzed by the Western blot analysis. The Bcl-2 expression was inhibited and the ratio of Bax/Bcl-2 expression increased at 50μM and 100μM oleic acid. The apoptosis-related proteins (Fas, cytochrome C, Apaf-1, caspase 3) were increased by 50μM and 100μM EPA. In contrast, there was not the significant change in expression of apoptosis-related proteins (Fas, cytochrome C, Apaf-1, caspase 3) at 50μM and 100μM oleic acid. Moreover, EPA significantly increased the activity of caspase 3, while oleic acid did not affect the caspase 3 activity. Our results indicate that the apoptosis of HeLa cells by oleic acids might be through caspase-independent mechanism. We also analyzed the change of NF-κB , IκBα and IκBβ, to which have been, recently, paid much attention with relation to apoptosis. We found that NF-κB was dose-dependently inhibited by oleic acid and IκBβ was dose-dependently increased, although there was no change in IκBα. Our results suggest that the apoptosis by oleic acids might be associated with IκBβ, indicating that the mechanism of apoptosis by oleic acid might be different from those by EPA.
