Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid

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• 作者：Tetsuya Shirota ; Seiji Haji ; Mitsuo Yamasaki ; Takuya Iwasaki ; Toshiharu Hidaka ; Yoshifumi Takeyama ; Hitoshi Shiozaki and Harumasa Ohyanagi
• 刊名：Nutrition
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：21
• 期：10
• 页码：1010-1017
• 全文大小：394 K

文摘

Objectives

Clinical studies have shown that administration of eicosapentaenoic acid (EPA) to patients who have unresectable pancreatic cancer induces marked attenuation of cachexia. However, the exact mechanisms of the beneficial effect of EPA on pancreatic cancer are unknown. This examined the effect of EPA on proliferation of human pancreatic cancer cell lines and sought to clarify its mechanisms.

Methods

The effects of EPA on proliferation of three human pancreatic cancer cell lines (SW1990, AsPC-1, and PANC-1) were assessed. Induction of apoptosis and expressions of apoptosis-related proteins were measured. The effect of EPA on cyclo-oxygenase–2 expression in these cell lines was determined.

Results

EPA inhibited proliferation of all three human pancreatic cancer cell lines in a dose-dependent fashion. Simultaneously, EPA treatment induced apoptosis and this was associated with caspase-3 activation. EPA treatment was also associated with a decrease in intracellular levels of cyclo-oxygenase–2 protein.

Conclusion

We have demonstrated that EPA inhibits human pancreatic cancer cell growth due at least in part to the induction of apoptotic cell death. Such apoptosis is associated with activation of caspase-3 and suppression of cyclo-oxygenase–2 expression. Greater understanding of the molecular events associated with the biological activity of EPA should enhance the therapeutic potential of administration of EPA to patients who have pancreatic cancer.