Conjugated Linoleic Acid as a Tumor Preventive Agent

  • David Kritchevsky
  • Michael W. Pariza
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Carcinogens—e.g., benzo[a]pyrene (B[a]P) and 2-amino-3-methylimidazo[4,5f]-quinoline (IQ)—may be formed during flame broiling of protein-rich foods such as meat or fish (1–3). Pariza et al. (4), in the course of studying effects of controlled cooking temperature on mutagen formation in hamburger, found both mutagenic and antimutagenic activity. This activity was also found in uncooked hamburger. In further research, Pariza et al. (5) showed that the partially purified fraction (then called mutagenesis modulator) could inhibit IQ-induced mutagenicity in the Ames test (6). Before its chemical structure was established, Pariza and Hargraves (7) demonstrated that the mutagenesis modulator also inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermal neoplasia in mice (Table 1). In 1987, Ha et al. (8) established that the material they had referred to a mutagenesis modulator was a mixture of isomers of conjugated linoleic acid (CLA).


Linoleic Acid Conjugated Linoleic Acid Dietary Conjugated Linoleic Acid Conjugated Linoleic Acid Content Furan Fatty Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lijinsky W, Shubik P. Benzo(a)pyrene and other polynuclear hydrocarbons in charcoal broiled meat. Science 1974;145:53–55.CrossRefGoogle Scholar
  2. 2.
    Dipple A. Formation, metabolism and mechanism of action of polycyclic aromatic hydrocarbons. Cancer Res 1983;43:2422S-2425S.PubMedGoogle Scholar
  3. 3.
    Wakabayashi K, Nagao M, Esumi H, Sugimura T. Food derived mutagens and carcinogens. Cancer Res 1992;52:2092S-2098S.PubMedGoogle Scholar
  4. 4.
    Pariza MW, Ashoor SH, Chu FS, Lund DB. Effects of temperature and time on mutagen formation in pan-fried hamburger. Cancer Lett 1979;7:63–69.PubMedCrossRefGoogle Scholar
  5. 5.
    Pariza MW, Loretz, LJ, Storkson JM, Holland NC. Mutagens and modulator of mutagenesis in fried ground beef. Cancer Res 1983;43:2444S-24446S.PubMedGoogle Scholar
  6. 6.
    Ames BN, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with Salmonella/mammalian microsomes mutagenicity tests. Mutat Res 1975;31:347–364.PubMedCrossRefGoogle Scholar
  7. 7.
    Pariza MW, Hargraves WA. A beef derived mutagenesis modulator inhibits initiation of mouse epidermal tumors by 7,12-dimethylbenz(a) anthracene. Carcinogenesis 1985;6:591–593.PubMedCrossRefGoogle Scholar
  8. 8.
    Ha YL, Grimm NK, Pariza MW. Anti-carcinogens from fried ground beef: heat altered derivatives of linoleic acid. Carcinogenesis 1987;8:1881–1887.PubMedCrossRefGoogle Scholar
  9. 9.
    Parodi PW. Conjugated linoleic acid: the early years, in Advances in Conjugated Linoleic Acid Research, vol. 1. Yurawecz MP, Mossaba MM, Kramer JKG, et al., eds. AOCS Press, Champaign, IL, 1999, pp. 1–11.Google Scholar
  10. 10.
    Kepler CR, Hirons KP, McNeill JJ, Tove SB. Intermediates and products of the biohydrogenation of linoleic acid by Butyrivibrio fibrisolvens. J Biol Chem 1966;241:1350–1354.Google Scholar
  11. 11.
    Kepler CR, Tove SB. Biohydrogenation of unsaturated fatty acids. III. Purification and properties of a linoleate Δ12-cis, A’ 1 -trans from Butyrivibrio fibrisolvens. J Biol Chem 1967;242:5686–5692.Google Scholar
  12. 12.
    Ha YL, Storkson JM, Pariza MW. Inhibition of benzo[a]pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res 1990;50:1097–1101.PubMedGoogle Scholar
  13. 13.
    Ip C, Chin SF, Scimeca JA, Pariza MW. Mammary cancer prevention by conjugated dienoic derivative of linoleic acid. Cancer Res 1991;51:6118–6124.PubMedGoogle Scholar
  14. 14.
    Ip C, Singh M, Thompson HJ, Scimeca JA. Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat. Cancer Res 1994;54:1212–1215.PubMedGoogle Scholar
  15. 15.
    Ip C, Scimeca JA, Thompson H. Effect of timing and duration of dietary conjugated linoleic acid on mammary cancer prevention. Nutr Cancer 1995;24:241–247.PubMedCrossRefGoogle Scholar
  16. 16.
    Welsch CW. Relationship between dietary fat and experimental mammary tumorigenesis: a review and critique. Cancer Res 1992;52:2040S-2048S.PubMedGoogle Scholar
  17. 17.
    Ip C, Briggs SP, Haegele AD, et al. The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level or type of fat in the diet. Carcinogenesis 1996;17:1045–1050.PubMedCrossRefGoogle Scholar
  18. 18.
    Ip C, Scimeca JA. Conjugated linoleic acid and linoleic acid are distinctive modulators of mammary carcinogenesis. Nutr Cancer 1997;27:131–135.PubMedCrossRefGoogle Scholar
  19. 19.
    Liew C, Schut HAJ, Chin SF, et al. Protection of conjugated linoleic acids against 2-amino-3-methylimidazo[4,5f]quinoline-induced colon carcinogenesis in the F344 rat: a study of inhibitory mechanisms. Carcinogenesis 1995:16:3037–3043.PubMedCrossRefGoogle Scholar
  20. 20.
    Belury MA, Nickel KP, Bird CE, Wu Y. Dietary conjugated linoleic acid modulation of phorbol ester skin tumor promotion. Nutr Cancer 1996;26:149–157.PubMedCrossRefGoogle Scholar
  21. 21.
    Cesano A, Hoxie JA, Lange B, et al. The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemia. Oncogene 1992;7:827–836.PubMedGoogle Scholar
  22. 22.
    Visonneau S, Cesano A, Tepper SA, et al. Conjugated linoleic acid suppresses the growth of human breast adenocarcinoma cells in SCID mice. Anticancer Res 1997;17:969–974.PubMedGoogle Scholar
  23. 23.
    Cesano A, Visonneau S, Scimeca JA, et al. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res 1998;18:833–838.Google Scholar
  24. 24.
    Visonneau S, Cesano A, Tepper SA, et al. Effect of different concentrations of conjugated linoleic acid (CLA) on tumor cell growth in vitro. FASEB J 1996;10:A182.Google Scholar
  25. 25.
    Shultz TD, Chew BP, Seaman WR, Luedecke LO. Inhibitory effect of conjugated diene derivatives of linoleic acid and (3 carotene on the in vitro growth of human cancer cells. Cancer Lett 1992;63:125–133.PubMedCrossRefGoogle Scholar
  26. 26.
    Schultz TD, Chew BP, Seaman WR. Differential stimulatory and inhibitory responses of human MCF-7 breast cancer cells to linoleic acid and conjugated linoleic acid in culture. Anticancer Res 1992;12:2143–2146.Google Scholar
  27. 27.
    Cunningham DC, Harrison LY, Shultz TD. Proliferative response of normal human mammary and MCF-7 breast cancer cells to linoleic acid, conjugated linoleic acid and eicosanoid synthesis inhibitors in culture. Anticancer Res 1997;17:197–204.PubMedGoogle Scholar
  28. 28.
    Durgam VR, Fernandes G. The growth inhibitory effect of conjugated linoleic acid on MCF-7 cells is related to estrogen response system. Cancer Lett 1997;116:121–130.PubMedCrossRefGoogle Scholar
  29. 29.
    Schonberg S, Krokan HE. The inhibitory effect of conjugated dienoic derivatives (CLA) of linoleic acid on the growth of human tumor cell lines is in part due to increased lipid peroxidation. Anticancer Res 1995;15:1241–1246.PubMedGoogle Scholar
  30. 30.
    Igarashi M, Miyazawa T. The growth inhibitory effect of conjugated linoleic acid on a human hepatoma cell line, HepG2 is induced by a change in fatty acid metabolism, but not the facilitation of lipid peroxidation in the cells. Biochim Biophys Acta 2001;1530:162–171.PubMedCrossRefGoogle Scholar
  31. 31.
    Wattenberg L. Chemoprevention of cancer. Cancer Res 1985;45:1–8.PubMedCrossRefGoogle Scholar
  32. 32.
    van den Berg JJ, Cook NE, Tribble DL. Reinvestigation of the antioxidant properties of conjugated linoleic acid. Lipids 1995;30:599–605.PubMedCrossRefGoogle Scholar
  33. 33.
    Chen ZY, Chan PT, Kwan KY, Zhang A. Reassessment of the antioxidant activity of conjugated linoleic acid. J Am Oil Chem Soc 1997;74:719–753.CrossRefGoogle Scholar
  34. 34.
    Yurawecz MP, Hood JK, Mossaba MM, et al. Furan fatty acids determined as oxidation products of conjugated octadecadienoic acid. Lipids 1995;30:595–598.PubMedCrossRefGoogle Scholar
  35. 35.
    Wamer W, Yurawecz MP, Wei R, et al. In vitro assessment of cytotoxicity and antioxidant activity of a furan fatty acid, a novel oxidation product of conjugated linoleic acid. FASEB J 1996;10:A272.Google Scholar
  36. 36.
    Zu HX, Schut HAJ. Inhibition of 2-amino-3-methylimidazo[4,5f]quinoline-DNA adduct formation in CDF1 mice by heat altered derivatives of linoleic acid. Food Chem Toxicol 1992;30:9–16.PubMedGoogle Scholar
  37. 37.
    Schut HAJ, Cummings DA, Smale MHE, et al. DNA adducts of heterocylic amines: formation, removal and inhibition by dietary components. Mutat Res 1997;376:185–194.PubMedCrossRefGoogle Scholar
  38. 38.
    Josyula S, He YH, Ruch RJ, Schut HAJ. Inhibition of DNA adduct formation of PhIP in female F344 rats by dietary conjugated linoleic acid. Nutr Cancer 1998;32:132–138.PubMedCrossRefGoogle Scholar
  39. 39.
    Josyula S, Schut HAJ. Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats. Nutr Cancer 1998;32:139–145.PubMedCrossRefGoogle Scholar
  40. 40.
    Sugano M, Tsujita A, Yamasaki M, et al. Lymphatic recovery, tissue distribution, and metabolic effects of conjugated linoleic acid in rats. J Nutr Biochem 1997;8:38–43.CrossRefGoogle Scholar
  41. 41.
    Cook ME, Miller CC, Park Y, Pariza M. Immune modulation by altered nutrient metabolism: nutritional control of immuneinduced growth depression. Poultry Sci 1993;72:1301–1306.CrossRefGoogle Scholar
  42. 42.
    Park Y, Pariza MW. Lipoxygenase inhibitors inhibit heparinreleasable lipoprotein lipase activity in 3T3-L1 adipocytes and enhance body fat reduction in mice by conjugated linoleic acid. Biochim Biophys Acta 2001;1534:27–33.PubMedCrossRefGoogle Scholar
  43. 43.
    Miller A, Stanton C, Devery R. Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF-7 and SW480 cancer cells. Lipids 2001;36:1161–1168.PubMedCrossRefGoogle Scholar
  44. 44.
    Belury MA, Vanden Heuvel JP. Modulation of diabetes by conjugated linoleic acid in Yurawicz MP, Mossaba MM, Kramer JKG, et al., eds. Advances in Conjugated Linoleic Acid Research, vol. 1. AOCS Press, Champaign, IL,1999, pp.404–411.Google Scholar
  45. 45.
    Moody DE, Reddy JK, Lake B, et al. Peroxisomers proliferation and nongenotoxic carcinogenesis. Commentary of a symposium. Fundam Appl Toxicol 1991;16:233–248.PubMedCrossRefGoogle Scholar
  46. 46.
    Peters JM, Park Y, Gonzalez FJ, Pariza MW. Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferatoractivated receptor a-null mice. Biochim Biophys Acta 2001;1533:233–242.PubMedCrossRefGoogle Scholar
  47. 47.
    Farquharson A, Wu HC, Grant I, et al. Possible mechanisms for the putative antiatherogenic and antitumorigenic effects of conjugated polyenoic fatty acids. Lipids 1999;34:5343.CrossRefGoogle Scholar
  48. 48.
    Ip C, Jiang C, Thompson HJ, Scimeca JA. Retention of conjugated linoleic acid in the mammary gland is associated with tumor inhibition during the post-initiation phase of carcinogenesis. Carcinogenesis 1997;18:755–759.PubMedCrossRefGoogle Scholar
  49. 49.
    Kneckt P, Jarvinen R, Seppanen R, et al. Intake of dairy products and the risk of breast cancer. Br J Cancer 1996;73:687–691.CrossRefGoogle Scholar
  50. 50.
    Knekt P, Järvinen R. Intake of dairy products and breast cancer risk, in Yurawecz MP, Mossaba MM, Kramer JKG, et al., eds. Advances in Conjugated Linoleic Acid Research, vol. 1. AOCS Press, Champaign, IL, 1999, pp.444–470.Google Scholar
  51. 51.
    Lavillonniere F, Bougnoux P. Conjugated linoleic acid (CLA) and the risk of breast cancer,. In Yurawecz MP, Mossaba MM, Kramer JKG, Pariza MW, Nelson GJ, eds. Advances in Conjugated Linoleic Acid Research, vol. 1. AOCS Press, Champaign, IL, 1999, pp.276–282.Google Scholar
  52. 52.
    Aro A, Männesto S, Salminen I, et al. Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women. Nutr Cancer 2000;38:151–157.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • David Kritchevsky
  • Michael W. Pariza

There are no affiliations available

Personalised recommendations