Conjugated linoleic acid reduced metastasized LL2 tumors in mouse peritoneum.
The effect of conjugated linoleic acid (CLA) on pre-existent peritoneal metastasis was examined by mouse peritoneal metastasis models. The cell growth of LL2 mouse cancer cells was suppressed by CLA in a dose-dependent manner. CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma. C57B6 mice were inoculated with LL2 cells into their peritoneal cavity. Two weeks after inoculation, colonized peritoneal cancer foci (2.2+/-0.4 mm in diameter) were treated with CLA administrated intraperitoneally (200 or 600 pmol/mouse, twice a week). CLA treatment decreased the number of peritoneal tumors: 8.7+/-0.6, 5.7+/-0.6, and 2.3+/-0.6 in untreated, 200 pmol/mouse CLA, and 600 pmol/mouse CLA groups, respectively (P<0.0001). CLA treatment decreased the size of peritoneal tumors: 3.7+/-1.5, 1.3+/-0.5, and 1.0+/-0.4 mm in untreated, 200 pmol/mouse CLA, and 600 pmol/mouse CLA groups, respectively (P<0.0001). In CLA-treated tumors, proliferating cells were decreased (P<0.0001), whereas apoptotic cells were increased (P=0.0010). CLA-treated LL2 tumors showed decrease of PPARgamma and EGFR proteins and increase of BAX protein in comparison with untreated tumors. These findings suggest that CLA possesses anti-tumor capability to peritoneal metastasis.
Sakai
Yasuha
Y
Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Japan.
Sasahira
Tomonori
T
Ohmori
Hitoshi
H
Yoshida
Kazuhiro
K
Kuniyasu
Hiroki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D007274:Injections, Intraperitoneal; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D016376:Oligonucleotides, Antisense; D047495:PPAR gamma; D018809:Proliferating Cell Nuclear Antigen