Linoleic-acid-induced growth suppression induces quiescent cancer cell nests in nude mice.
We examined the effect of linoleic acid (LA) on tumor formation. Cell growth was suppressed by LA in a dose-dependent manner in MKN28 and Colo320 cells. Continuous treatment with LA provided growth arrest in both cells at 5-7 weeks after the treatment. LA-pretreated MKN28 and Colo320 cells showed higher tumorigenicity (9/10 and 10/10, respectively) than nontreated cells (2/10 and 3/10, respectively; p < 0.01) in nude mice. In contrast, LA-pretreated MKN28 and Colo320 cells showed more suppressed tumor growth than nontreated cells (p < 0.01). LA-pretreated MKN28 and Colo320 cells with LA administration after the inoculation did not form macroscopic tumors. Histological examination revealed small cancer cell aggregations, which showed no proliferative activity. In LA-treated MKN28 and Colo320 cells, protein production of Bcl-2 was increased, whereas Bak, EGFR and VEGF levels were decreased. These findings suggest that LA might induce quiescence and subsequent dormancy in cancer cells.
Ohmori
Hitoshi
H
Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
Sasahira
Tomonori
T
Fujii
Kiyomu
K
Yi
Luo
L
Shimomoto
Takasumi
T
Kuniyasu
Hiroki
H
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D050998:bcl-2 Homologous Antagonist-Killer Protein; D019787:Linoleic Acid; D066246:ErbB Receptors