Skip to main content

Advertisement

SpringerLink
Log in

Peritoneal metastasis inhibition by linoleic acid with activation of PPARγ in human gastrointestinal cancer cells

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The effect on peritoneal metastasis of linoleic acid (LA) was examined using in vitro treatment of cancer cells and mouse peritoneal metastasis models. Firstly, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by LA in a dose-dependent manner with increment of apoptosis. LA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor gamma (PPARγ) or 15-lipoxygenase-1, which converts LA to PPARγ ligands. LA significantly inhibited invasion into type-IV collagen-coated membrane of MKN28 and Colo320 cells (p<0.05). BALB/c nu/nu mice inoculated with MKN28 and Colo320 cells into their peritoneal cavities were administrated with LA intraperitoneally (weekly, four times). The LA treatment significantly diminished the number of metastatic foci of both cells in the peritoneal cavity (p<0.05). Protein production in MKN28 and Colo320 cells treated with LA showed a decrease of epidermal growth factor receptor and an increase of Bax. These findings suggest that LA inhibits invasion and metastasis of human gastric and colon cancer cells by nondietary administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

LA:

Linoleic acid

ODN:

Oligodeoxynucleotide

PPAR:

Peroxisome proliferator-activated receptor

LOX:

Lipoxygenase

EGFR:

Epidermal growth factor receptor

PG:

Prostaglandin

HODE:

Hydroxyoctadecadienoic acid

OXO:

Oxooctadecadienoic acid

CLA:

Conjugated linoleic acid

PBS:

Phosphate-buffered saline

References

  1. Badawi AF, Eldeen MB, Liu Y, Ross EA, Badr MZ (2004) Inhibition of rat mammary gland carcinogenesis by simultaneous targeting of cyclooxygenase-2 and peroxisome proliferator-activated receptor γ. Cancer Res 64:1181–1189

    Article  PubMed  CAS  Google Scholar 

  2. Belury MA (2002) Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 132:2995–2998

    PubMed  CAS  Google Scholar 

  3. Chang WC, Chapkin RS, Lupton JR (1997) Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis. Carcinogenesis 18:721–730

    Article  PubMed  CAS  Google Scholar 

  4. Chen A, Xu J (2004) Activation of PPARγ by curcumin inhibits Moser cell growth and mediates the suppression of the gene expression of cyclinD1 and EGFR. Am J Physiol Gastrointest Liver Physiol 14:14

    CAS  Google Scholar 

  5. Gupta RA, Dubois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21

    Article  PubMed  CAS  Google Scholar 

  6. Kuniyasu H, Yasui W, Kitahara K, Naka K, Yokozaki H, Akama Y, Hamamoto T, Tahara H, Tahara E (1997) Growth inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line. Cell Growth Differ 8:47–52

    PubMed  CAS  Google Scholar 

  7. Liu JJ, Huang RW, Lin DJ, Peng J, Wu XY, Lin Q, Pan XL, Song YQ, Zhang MH, Hou M, Chen F (2005) Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-γ ligands induces apoptosis on human myeloid leukemia cells in vitro. Ann Oncol 10:10

    Google Scholar 

  8. Majumder B, Wahle KW, Moir S, Schofield A, Choe SN, Farquharson A, Grant I, Heys SD (2002) Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells. FASEB J 16:1447–1449

    PubMed  CAS  Google Scholar 

  9. Miller A, Stanton C, Devery R (2002) Cis 9, trans 11- and trans 10, cis 12-conjugated linoleic acid isomers induce apoptosis in cultured SW480 cells. Anticancer Res 22:3879–3887

    PubMed  CAS  Google Scholar 

  10. Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM (1998) Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell 93:229–240

    Article  PubMed  CAS  Google Scholar 

  11. Osawa E, Nakajima A, Wada K, Ishimine S, Fujisawa N, Kawamori T, Matsuhashi N, Kadowaki T, Ochiai M, Sekihara H, Nakagama H (2003) Peroxisome proliferator-activated receptor γ ligands suppress colon carcinogenesis induced by azoxymethane in mice. Gastroenterology 124:361–367

    Article  PubMed  CAS  Google Scholar 

  12. Rao CV, Hirose Y, Indranie C, Reddy BS (2001) Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res 61:1927–1933

    PubMed  CAS  Google Scholar 

  13. Reddy BS, Burill C, Rigotty J (1991) Effect of diets high in ω-3 and ω-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis. Cancer Res 51:487–491

    PubMed  CAS  Google Scholar 

  14. Singh J, Hamid R, Reddy BS (1997) Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res 57:3465–3470

    PubMed  CAS  Google Scholar 

  15. Sugarbaker PH (2002) New responsibilities in the management of colorectal cancer with peritoneal seeding. Cancer Invest 20:1118–1122

    Article  PubMed  Google Scholar 

  16. Sugarbaker PH, Yu W, Yonemura Y (2003) Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy: the evolution of treatment strategies for advanced gastric cancer. Semin Surg Oncol 21:233–248

    Article  PubMed  Google Scholar 

  17. Terashita Y, Sasaki H, Haruki N, Nishiwaki T, Ishiguro H, Shibata Y, Kudo J, Konishi S, Kato J, Koyama H, Kimura M, Sato A, Shinoda N, Kuwabara Y, Fujii Y (2002) Decreased peroxisome proliferator-activated receptor γ gene expression is correlated with poor prognosis in patients with esophageal cancer. Jpn J Clin Oncol 32:238–243

    Article  PubMed  Google Scholar 

  18. Vogel I, Kalthoff H (2001) Disseminated tumour cells. Their detection and significance for prognosis of gastrointestinal and pancreatic carcinomas. Virchows Arch 439:109–117

    Article  PubMed  CAS  Google Scholar 

  19. Yoshizumi T, Ohta T, Ninomiya I, Terada I, Fushida S, Fujimura T, Nishimura G, Shimizu K, Yi S, Miwa K (2004) Thiazolidinedione, a peroxisome proliferator-activated receptor-γ ligand, inhibits growth and metastasis of HT-29 human colon cancer cells through differentiation-promoting effects. Int J Oncol 25:631–639

    PubMed  CAS  Google Scholar 

  20. Zhou S, Wang G, Chen B, Wang P (2000) Effect of dietary fatty acids on tumorigenesis of colon cancer induced by methyl nitrosourea in rats. J Environ Pathol Toxicol Oncol 19:81–86

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Kaori Isobe for expert assistance with the preparation of this manuscript. This research was supported by Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science and Grant-in-Aid for Scientific Research from Mitsui Memorial Fund.

Author information

Authors and Affiliations

  1. Department of Molecular Pathology, Nara Medical University, Kashihara, Japan

    Takamitsu Sasaki, Kiyomu Fujii, Tomonori Sasahira, Hitoshi Ohmori & Hiroki Kuniyasu

  2. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Kazuhiro Yoshida

  3. First Department of Surgery, Fukuoka University School of Medicine, Fukuoka, Japan

    Hideo Shimura

Authors
  1. Takamitsu Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kiyomu Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideo Shimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomonori Sasahira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hitoshi Ohmori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroki Kuniyasu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroki Kuniyasu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sasaki, T., Fujii, K., Yoshida, K. et al. Peritoneal metastasis inhibition by linoleic acid with activation of PPARγ in human gastrointestinal cancer cells. Virchows Arch 448, 422–427 (2006). https://doi.org/10.1007/s00428-005-0110-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-005-0110-4

Keywords

Search

Navigation