The traditional diet of Greece and cancer.

[R.B.]

Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane
Paola A Corsetto,1 Gigliola Montorfano,1 Stefania Zava,1 Ilaria E Jovenitti,1 Andrea Cremona,1 Bruno Berra,1 and Angela M Rizzocorresponding author1
1Dipartimento di Scienze Molecolari Applicate ai Biosistemi, UniversitÃ* degli Studi di Milano, Italy

(Full Free Text)

http://www.ncbi.nlm.nih.gov/pmc/arti...tool=pmcentrez

Background
PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells.

Methods
Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane.
Results
We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR.
N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa.

Conclusions
Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

[R.B.]

Hi All

Apologies I managed to duplicate a reference above.

The ongoing saga of dental infection continues, and my suspicion that dental infections can fog the brain remains. My childhood hockey accident broken root filled and refilled and apisectomied tooth [twice] appears to have been reinfecting the bone through escape of bacteria living in the space where the post sits - the tooth and a neighbouring tooth have now been removed - not a good look (-: - but hopefully the recurring infection in the bone in the area and likely higher in the face which has been going on to greater and lesser extent for several years, now may clear up.

This is a fascinating summary adding to the evidence excess linoleic acid (plant based 18 carbon Omega Six which makes up 50 - 70 % of the fat in many vegetable oils, and arguably which many of us get too much of) is a factor in BC.


Int J Biochem Cell Biol. 2011 Sep 16. [Epub ahead of print]
Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A.
Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, Salazar EP.
Source

Departamento de Biologia Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
Abstract

Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Epithelial-mesenchymal-transition (EMT) is a process, by which epithelial cells are transdifferentiated to a mesenchymal state, and it has been implicated in cancer progression, including invasion and metastasis. Linoleic acid (LA) induces proliferation and invasion in breast cancer cells. However, the role of LA on the EMT process in human mammary epithelial cells remains to be studied. In the present study, we demonstrate that LA induces a transient down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2, Twist1, Twist2 and Sip1 expressions. Furthermore, LA induces FAK and NFκB activation, MMP-2 and -9 secretions, migration and invasion. In summary, our findings demonstrate, for the first time, that LA promotes an EMT-like process in MCF10A human mammary epithelial cells.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
21945809
[PubMed - as supplied by publisher]

[R.B.]

More Omega 3 and 6 mechanisms which affect cancer cell function (-:

Omega 6 derivatives are the main natural activators of pathways in which cannabis derivatives are also active, which has a host of implications, including in controlling mood, food intake, weight gain etc. As well as influencing brain function these Omega 6 compounds are also active in many cells, including the reproductive system. This paper suggests they affect proliferation in cancer cells.

It looks as if Omega 3 derivatives have different roles in these pathways to Omega 6 derivatives and once again the balance between the two appears to affect cell function. ( FYI anandamide and 2-arachidonoylglycerol are omega 6 based products - see below)

The involvement of cannabis receptors begs the question does cannabis affect cancer (increase or decrease) by inhibiting the access of other compounds to these pathways - scientists are looking a the effects of cannabis derivatives on cancer - and that in turn would depend on the balance of natural activators produced in the body, including through the Omega 3 and 6 pathways but the wider implications ??? These receptors are found widely in the body including in the brain, and I value the function of mine.



Prostaglandins Leukot Essent Fatty Acids. 2011 Oct 11. [Epub ahead of print]
Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines.
Brown I, Wahle KW, Cascio MG, Smoum-Jaouni R, Mechoulam R, Pertwee RG, Heys SD.
Source

Translational Medical Sciences, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Abstract

Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
21995886
[PubMed - as supplied by publisher]

[R.B.]

This is neat because it relates the Omega 3:6 profile of strictly controlled diet to what is happening in prostate cancer cells in living humans. The diet was tested in the time frame whilst patients were awaiting surgical removal of cancerous tissue, which tissue was then available for examination as to the effect of the different diets on cancer cell fat composition, structure, cell division rate, etc. The trial is small but has prompted a bigger trial


http://www.newswise.com/articles/you...e-cancer-cells

You are What You Eat: Low-Fat Diet with Fish Oil Slowed Growth of Human Prostate Cancer Cells
Released: 10/25/2011 7:00 AM EDT
Source: University of California, Los Angeles (UCLA), Health Sciences

"Newswise — A low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed down the growth of prostate cancer cells – the number of rapidly dividing cells – in human prostate cancer tissue compared to a traditional, high-fat Western diet.

Done by researchers at UCLA’s Jonsson Comprehensive Cancer Center, the short-term study also found that the men on the low-fat, fish oil supplement diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, though further studies are needed, said Dr. William Aronson, the study’s first author and a researcher with UCLA’s Jonsson Comprehensive Cancer Center.

The study also found that blood obtained from patients after the low-fat, fish oil diet program slowed the growth of prostate cancer cells in a test tube as compared to blood from men on the Western diet, which did not slow cancer growth.

“The finding that the low-fat, fish oil diet reduced the number of rapidly dividing cells in the prostate cancer tissue is important because the rate at which the cells are dividing can be predictive of future cancer progression,” Aronson said. “The lower the rate of proliferation, the lesser the chances that the cancer will spread outside the prostate, where it is much harder to treat.” . . .

"- the “treatment” was indeed reaching the targeted organ because of the changes in the prostate cell membrane’s fatty acid composition." . . .

"Diet studies often are difficult to evaluate because getting patients to comply with dietary changes can be challenging. However, the food eaten by men in both arms of this study was precisely controlled, Aronson said. The meals were prepared by chefs in the UCLA Clinical Translational Research Center and delivered in bulk to study participants several times a week. Participants also met with a dietician, kept food diaries and were required to return uneaten food."


"
The study appeared Oct. 25, 2011 in Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research."

[Andrea Barnett Budin]

For goodness sakes -- IS THERE NO END TO THE MANY WAYS IN WHICH OMEGA 3 BENEFITS US ALL...???

Hi, RB! Can you list some of the diseases and ailments Omega 3 can alter our lives? Just in a neat little package. (I've read your book, and am ever impressed with it's messages.)

I know people in their 40s, 50s, 60s, 70s, and 80s who are on to this life-saver!

I take 2 a day. Every day...

[R.B.]

Hi Andrea

Great to your positive posts. Thanks for the kind words. The book is not very well written, but the science in it is generally fine, and I am well received at specialist conferences on lipids on the strength of it. It raises important issues, is thought provoking, but is a bit disjointed and best read in small sections - it leaves lots of questions and that is because this is a developing area of science and much is still simply not known - if the book gets you to realise that excess Omega 6 (and not enough Omega 3) in our diet is an important issue it is a positive step - I stand by some of the more sweeping claims - excess Omega 6 will be seen in the future to be a very serious health issue - I have largely rewritten an expanded book, which is much fuller and more confidently written, and ties in other areas, but I need to find some serious time to finish it - the researchers that are doing all the fine work that made the book and rewrite possible are way ahead of their time.

One of the pieces of good news is that the US military are beginning to take the subject seriously, and they really do have the power to influence food production and composition.

Excess Omega 6 is strongly connected with the ability to reproduce and all of the processes that entails. Excess omega 6 is a factor in many western conditions, and particularly those that are inflammation related. I will try and find time over the weekend to add a list.

(For anyone who has read the biography at the back the issue is still ongoing, and it was disclosed at a recent Freedom of Information Tribunal seeking disclosure of a secret practice direction dealing with the closure of Royal wills that the document related to a secret illegitimate royal child; so the claim may not be as batty as it sounds.)

[R.B.]

Some of you may also have seen the vitamin D threads in the nutrition section that suggest those with 'higher' levels of vitamin D on average have a lower risk of BC / recurrence.

The body is enormously complicated and interlinked as is evidenced by the paper below. The study suggests there may be links between the vitamin D pathways and Omega 6 pathways. PGE2 (a prostaglandin) is an oxidised downstream product of the 20 carbon fat called arachidonic acid (a member of the Omega 6 family, its name is explained by the fact it was first isolated from a spider). PGE2 features in lots of body functions, including inflammation, and hormone production.

The paper suggests links between a combination of increased Omega 6 PGE2 and lower Vitamin D (calcitriol) in breast cancer patients - double trouble.

Another paper on vitamin D and cancer below suggests a mechanism. Vitamin D is suggested to regulate enzymes that produce and dispose of prostaglandins including one called COX2, which is the enzyme that allows PGE2 to be made.

As a very broad generalisation Omega 3 competes for the same enzymes as Omega 6, and those with lower Omega 6 tend to have lower levels of Omega 6 products including PGE2 in their systems. In this way increased Omega 3 and lower Omega 6 may reduce the risk of a number of conditions including an array of cancers including BC and prostate cancer

A significant number of non-steroidal drugs commonly block the production or action of PGE2, which may explain why they and asprin may be associated with a reduction in the risk of cancer - but have other side effects



"Prostaglandin Metabolising Enzymes and PGE2 are Inversely Correlated with Vitamin D Receptor and 25(OH)2D3 in Breast Cancer

http://ar.iiarjournals.org/content/30/5/1673.abstract

Abstract

Background: Breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression. The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. First data suggest a correlation between vitamin D and prostaglandin metabolism. Materials and Methods: We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP2/EP4 in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)2D3 and PGE2 plasma levels from healthy and breast cancer patients. Results: Significantly higher COX-2, lower VDR and lower EP2 and EP4 receptor protein levels in the malignant tissue and a significantly lower 15-PGDH protein level in normal breast tissue were detected. Breast cancer patients older than 45 years, diagnosed and sampled in the wintertime had significantly lower 25(OH)2D3 and higher PGE2 serum levels. Conclusion: The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE2 and 25(OH)2D3 levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism."

Vitamin D and cancer: current dilemmas and future research needs1,2,3
Cindy D Davis
1 From the Nutritional Sciences Research Group, National Cancer Institute, Rockville, MD

2 Presented at the National Institutes of Health conference "Vitamin D and Health in the 21st Century: an Update," held in Bethesda, MD, September 5–6, 2007.


(the paper includes the following quote)

"Vitamin D regulates many genes involved in prostaglandin metabolism. 1,25(OH)2D inhibits COX-2 expression and activity, inhibits expression of prostaglandin receptors, and increases prostaglandin catabolism by increasing expression of 15-prostaglandin dehydrogenase (25). In combination, these 3 mechanisms reduce prostaglandin levels and signaling, thereby attenuating the growth-stimulatory effects of prostaglandins in prostate cancer (25). Furthermore, 1,25(OH)2D and naproxen (a nonsteroidal antiinflammatory drug) act synergistically in vitro and inhibit prostate cancer cell growth more effectively than either alone in patients on the basis of a slowing of the prostate-specific antigen doubling time (25). Thus, by understanding the molecular targets for vitamin D, researchers can develop more effective strategies for cancer prevention and treatment. "