Effect of Dietary CLA Isomers on Apoptosis and Cell Proliferation in Colonic Mucosa of DMH-Treated Rats

식이에 첨가한 CLA Isomer가 쥐에서 대장점막의 세포사멸과 세포증식에 미치는 영향

  • 박현서 (경희대학교 생활과학대학 식품영양학과) ;
  • 권필수 (경희대학교 생활과학대학 식품영양학과) ;
  • 윤정한 (한림대학교 생명과학부) ;
  • 하영래 (경상대학교 응용생명과학부)
  • Published : 2003.09.01

Abstract

The study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid (CLA) isomers on colon carcinogenesis in 1,2-dimethylhydrazine (DMH)-treated rats by determining the levels of apoptosis, cell proliferation, eicosanoids and 1,2-diacylglycerol (DAG) in colonic mucosa. Sixty male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. BT group (no CLA contained), CLA-C group (cis-9, trans11 isomer contained), and CLA- T group (trans-10, cis-12 isomer contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 0.8% CLA isomers by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of l80mg per kg body weight. Two CLA isomers (c9t11 and t10c12) significantly increased the relative percentage of apoptosis but reduced cell proliferation in mucosal cell and also the levels of PGE$_2$, TXB$_2$, and DAG in colonic mucosa. However, there was no significant differences in anti-carcinogenic effect between c9t11 isomer and t10c12 isomer. Overall, colon carcinogenesis could be significantly inhibited by CLA isomers by increasing apoptosis and reducing cell proliferation, the levels of eicosanoids and DAG in colonic mucosa.

Keywords

References

  1. Progress in Lipid Research v.40 The biologically active isomers of conjugated linoleic acid Pariza,M.W.;Park,Y.H.;Cook,M.E. https://doi.org/10.1016/S0163-7827(01)00008-X
  2. J Nutr v.132 Inhibition of carcinogenesis by conjugated linoleic acid:potential mechanisms of action Belury,M.A.
  3. Cancer Epidemiol Biomarkers Prev v.9 no.7 Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor cells and premalignant lesions of the rat mammary gland Ip,C.;Ip,M.M.;Loftus,T.;Shoemaker,S.;Shea-Eaton,W.
  4. J Am Coll Nutr v.19 no.2 Conjugated linoleic acid and disease prevention:a review of current knowledge MacDonald,H.B. https://doi.org/10.1080/07315724.2000.10718082
  5. Cancer Letters v.127 Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in murine keratinocytes Liu,K.L.;Belury,M.A. https://doi.org/10.1016/S0304-3835(97)00479-5
  6. Brit J Nutr v.86 Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats:a possible mechanism of the anticarcinogenic effect by CLA Park,H.S.;Ryu,J.H.;Ha,Y.L.;Park,H.Y. https://doi.org/10.1079/BJN2001445
  7. Am J Physiol Regulatory Integrative Comp Physiol v.280 CLA reduces antigen-induced histamine and PGE2 release from sensitized guinea pig tracheae Whigham,L.D.;Cook,E.B.;Stahl,J.L.;Saban,R.;Bjorling,D.E.;Paraza,M.W.;Cook,M.E.
  8. Doctoral Dissertation Effect of dietary supplementation of conjugated linoleic acid on tumor incidence and colon carcinogenesis in I,2-dimethylhydrazine-treated rats Kim,K.H.
  9. J Cell Biol v.119 Identification of programmed cell death via specific labeling of nuclear DNA fragmentation Gavrieli,Y;Sherman,Y;Ben-Sasson,S.A. https://doi.org/10.1083/jcb.119.3.493
  10. J Histochem Cytochem v.35 Studies with anti-bromo deoxyuridine antibodies:II. Simultaneous immunocytochemical detection of antigen expression and DNA synthesis by in vivo labeling of mouse intestinal mucosa Schutte,B.;Reyders,M.M.J.;Bosman,F.T.;Blijham,G.H. https://doi.org/10.1177/35.3.3546484
  11. Advances in prostaglandin and thromboxane research v.5 Granstron,E.;Samuelson,B.;J.C.Frolich(ed.)
  12. Can J Biochem Physiol v.37 A rapid method of total lipid extraction and purification Bligh,E.G.;Dyer,W.J.
  13. Int J Biochem v.25 An increase in phosophatidic acid in the absence of changes in diacylglycerol in human platelets stimulated with ADP Duncan,E.M.;Lyoyd,J.V. https://doi.org/10.1016/0020-711X(93)90485-W
  14. Clin Chim Acta v.22 A colorimetric method for estimating serum triglycerides Fletcher,M.J. https://doi.org/10.1016/0009-8981(68)90041-7
  15. Toxicology Letters v.64-65 A programmed cell death and its protective role with particular reference to apoptosis Schulte-Hermann,R.;Bursch,W.;Kraupp-Grasl,B.;Oberhammer,F.;Wagner,A. https://doi.org/10.1016/0378-4274(92)90233-A
  16. Cancer Res v.55 Inhibition of apoptosis during development of colorectal cancer Bedi,A.;Pasricha,P.J.;Akhtar,A.J.;Barber,J.P.;Bedi,G.C.;Giar-diello,F.M.;Zehnbauer,B.A.;Hamilton,S.R.;Jones,R.J.
  17. Exp Cell Res v.250 Conjugated linolic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture Ip,M.M.;Masso-Welch,P.A.;Shoemaker,S.F.;Shea-Eaton,W.K.;Ip,C. https://doi.org/10.1006/excr.1999.4499
  18. Eur J Cancer v.34 no.7 Effect of anthraquinone-laxatives on the proliferation and urokinase secretion of normal, premalignant and malignant colonic epithelial cells Schorkhuber,M.;Richter,M.;Dutter,A.;Sontag,G.;Marian,B. https://doi.org/10.1016/S0959-8049(98)00037-9
  19. J Clin Pathol v.43 no.9 Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of sub-jects with polyps Wilson,R.G.;Smith,A.N.;Bird,C.C. https://doi.org/10.1136/jcp.43.9.744
  20. Biochim et Biophy Acta v.1438 Antiplatelet effects of conjugated linoleic acid isomers Truitt,A.;McNeill,G.;Vanderhoek,J.Y. https://doi.org/10.1016/S1388-1981(99)00055-4
  21. Cancer Res v.55 no.11 Dietary fat, fiber and carcinogen alter fecal diacylglycerol composition and mass Pickering,J.S.;Lupton,J.R.;Chapkin,R.S.
  22. Lipid v.34 Possible mechanism for the putative antiatherogenic and antitumorigenic effects of conjugated polyenoic fatty acid Farquharson,A.;Wu,H.-C.L.;Grant,I.;Graf,B.;Choung,J.-J.;Eremin,O.;Heys,S.;Wahle,K. https://doi.org/10.1007/BF02562337