Linoleic acid and Cancer: the Importance of Prostaglandins as Demonstrated by Manipulation of the COX enzymes

I’ve previously discussed on this blog my belief  that linoleic acid may have negative effect on cancer risk. Today I want to look at some experimental evidence regarding why this is.

First, consider the fact that linoleic acid is a substrate for the production arachidonic acid, which itself is converted into various prostaglandins by the cyclooxygenase enzymes COX 1 & 2. Now consider this:

  • A large number of epidemiological studies have found that taking NSAID drugs, which block both the cyclooxygenase enzymes from producing prostaglandins, is associated with a reduced risk of certain cancers (1-10).
  • Numerous animal experiments have found that administration of NSAID drugs reduces the susceptibility, progression, and/or development of cancer induced by a carcinogenic agent. This has been seen in cancer of the breast (11-19), colon (20-27), liver (28), prostate (29-32), and bladder (33-35).
  • Animal experiments have also found that increasing expression of cyclooxygenase seems to increase susceptibility to cancer (36-38) and that removing COX genes reduces cancer development in response to carcinogens (39-40).
  • It has been observed that variations of the COX genes in humans affects the rate of cancer development (41,42).
  • Human cancers have frequently been found to have increased levels and/or expression of the cyclooxygenase enzymes (43-56).
  • Finally, a few controlled human trials have found that NSAID drugs reduce the occurrence (57-60) and progression (61-62) of cancer, typically of the colon.

I believe this is further evidence supporting the negative role of linoleic acid in cancer. Consuming linoleic acid increases prostaglandin production in the body (63-66) and provides the substrate for prostaglandin production. As shown above, reducing the ability of the COX enzymes to produce prostaglandins seems to reduce cancer risk, and vis versa. Thus, this is likely an important reason why reducing one’s intake of linoleic acid will be beneficial to cancer prevention.

Citations:

1. http://www.ncbi.nlm.nih.gov/pubmed/15998950

2. http://www.ncbi.nlm.nih.gov/pubmed/15668504

3. http://www.ncbi.nlm.nih.gov/pubmed/15734963

4. http://www.nature.com/bjc/journal/v97/n4/full/6603874a.html

5. http://www.sciencedirect.com/science/article/pii/S001650850350018X

6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363879/

7. http://www.ncbi.nlm.nih.gov/pubmed/15764753

8. http://www.ncbi.nlm.nih.gov/pubmed/21813335

9. http://www.ncbi.nlm.nih.gov/pubmed/12496048

10. http://www.ncbi.nlm.nih.gov/pubmed/15998950

11. http://cancerres.aacrjournals.org/content/60/8/2101.short

12. http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2000.tb01030.x/abstract

13. http://www.sciencedirect.com/science/article/pii/0952327892900984

14. http://cancerres.aacrjournals.org/content/45/4/1803.abstract?ijkey=ece30360b89ebecc10f77c9e233d5f9ae2a5cc44&keytype2=tf_ipsecsha

15. http://www.ncbi.nlm.nih.gov/pubmed/21590235?dopt=Abstract

16. http://www.ncbi.nlm.nih.gov/pubmed/10652588

17. http://www.ncbi.nlm.nih.gov/pubmed/11848504

18. http://www.ncbi.nlm.nih.gov/pubmed/10697514

19. http://www.ncbi.nlm.nih.gov/pubmed/9464506?dopt=Abstract

20. http://cancerres.aacrjournals.org/content/58/3/409.short

21. http://cancerpreventionresearch.aacrjournals.org/content/4/12/2015.abstract

22. http://cancerres.aacrjournals.org/content/65/17/8022.abstract

23. http://carcin.oxfordjournals.org/content/19/11/1939.short

24. http://cancerres.aacrjournals.org/content/41/5/1954.abstract

25. http://carcin.oxfordjournals.org/content/13/6/1019.abstract

26. http://clincancerres.aacrjournals.org/content/11/4/1618.abstract

27. http://www.cancerletters.info/article/S0304-3835(99)00296-7/abstract

28. http://jjco.oxfordjournals.org/content/37/9/673.abstract

29. http://clincancerres.aacrjournals.org/content/11/5/1999.abstract

30. http://cancerres.aacrjournals.org/content/64/9/3334.short

31. http://clincancerres.aacrjournals.org/content/13/18/5480.abstract

32. http://www.sciencedirect.com/science/article/pii/S0022534705673211

33. http://mct.aacrjournals.org/content/5/2/329.abstract

34. http://cancerres.aacrjournals.org/content/62/2/356.short

35. http://cancerpreventionresearch.aacrjournals.org/content/2/11/951.abstract

36. http://www.jbc.org/content/281/18/12210.abstract

37. http://www.jbc.org/content/276/21/18563.abstract

38. http://www.pnas.org/content/99/19/12483.abstract

39. http://cancerres.aacrjournals.org/content/65/21/10113.short

40. http://www.stanford.edu/class/cbio101/coursework/oshima1996.pdf

41. http://www.nature.com/bjc/journal/v97/n4/full/6603874a.html

42. http://carcin.oxfordjournals.org/content/28/6/1197.abstract

43. http://clincancerres.aacrjournals.org/content/7/2/429.abstract

44. http://cancerres.aacrjournals.org/content/55/17/3785.short

45. http://www.pnas.org/content/94/7/3336.short

46. http://cancerres.aacrjournals.org/content/62/3/632.short

47. http://cancerres.aacrjournals.org/content/59/5/987.short

48. http://europepmc.org/abstract/MED/7926468

49. http://jnci.oxfordjournals.org/content/90/6/455.short

50. http://europepmc.org/abstract/MED/11729113

51. http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0045(20000101)42:1%3C73::AID-PROS9%3E3.0.CO;2-G/abstract

52. http://cancerres.aacrjournals.org/content/58/17/3761.short

53. http://cancerres.aacrjournals.org/content/58/22/4997.short

54. http://cancerres.aacrjournals.org/content/59/5/991.short

55. http://www.ncbi.nlm.nih.gov/pubmed/21533404

56. http://cancerres.aacrjournals.org/content/59/1/198.short

57. http://www.ncbi.nlm.nih.gov/pubmed/8385741

58. http://www.nejm.org/doi/full/10.1056/NEJMoa061652

59. http://www.nejm.org/doi/full/10.1056/NEJMoa021633

60. http://www.nejm.org/doi/full/10.1056/NEJMoa021735

61. http://clincancerres.aacrjournals.org/content/9/13/4756.short

62. http://gut.bmj.com/content/50/6/857.abstract

63. http://ajcn.nutrition.org/content/40/4/763.full.pdf

64. http://www.ncbi.nlm.nih.gov/pubmed/3992060

65. http://www.ncbi.nlm.nih.gov/pubmed/7137955

66. http://www.ncbi.nlm.nih.gov/pubmed/472473

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s