Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid.
OBJECTIVE
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.


CONCLUSIONS
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.
Shirota
Tetsuya
T
Department of Surgery, Kinki University School of Medicine, Osaka, Japan. tetsu515@surg.med.kindai.ac.jp
Haji
Seiji
S
Yamasaki
Mitsuo
M
Iwasaki
Takuya
T
Hidaka
Toshiharu
T
Takeyama
Yoshifumi
Y
Shiozaki
Hitoshi
H
Ohyanagi
Harumasa
H
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure
D052246:Cyclooxygenase 2 Inhibitors; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases