Docosahexaenoic Acid Reverses Epithelial-Mesenchymal Transition and Drug Resistance ...

[pjoshea13]

New Chinese cell study [1].

Docosahexaenoic Acid [DHA] is one of the two marine omega-3 fatty acids that people seem to have become bored with. Are supplements good or bad? Why do the softgels have an "off" taste? Is the oil oxidized, rancid, etc."I like to get my DHA from fish. For breakfast I might have a can of King Oscar sardines, on toast. Or kippers. I had fried oysters this morning. Canned Alaskan salmon can deliver a high dose. The Alaskan season was very short this year for fresh fish, and one can't always trust the fishmonger, who may not realize that he is selling cheap farmed salmon as Alaskan. The distinctive can is reliable, I feel. It is designed for Alaska - the empty cans take up less space than regular cans when stacked. Keeps shipping costs down. They are not be shipped to other States."Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina." [2]. Why would one risk insufficiency?From the study: "Drug resistance is a serious problem in cancer therapy. Growing evidence has shown that docosahexaenoic acid has anti-inflammatory and chemopreventive abilities. Studies have shown that autophagy inhibition and ferroptosis are promising therapeutic strategies for overcoming multidrug resistance.""DHA displayed anti-cancer effects on proliferation, colony formation, migration, apoptosis, autophagy and epithelial mesenchymal transition." (See below for more.)-Patrick[1] pubmed.ncbi.nlm.nih.gov/363...... This study was aimed to examine whether docosahexaenoic acid (DHA) could reverse docetaxel resistance in prostate cancer cells. Cell survival was examined by MTT and colony formation. Protein expression was determined by Western blot. Reactive oxygen species (ROS) production was measured by flow cytometry. DHA displayed anti-cancer effects on proliferation, colony formation, migration, apoptosis, autophagy and epithelial mesenchymal transition. Glutathione-S-transferase π is an enzyme that plays an important role in drug resistance. DHA inhibited GSTπ protein expression and induced cytoprotective autophagy by regulating the PI3K/AKT signalling pathway in PC3R cells. DHA combined with PI3K inhibitor (LY294002) enhanced apoptosis by alleviating the expression of LC3B, (pro-) caspase- 3 and (uncleaved) PARP. DHA induced ferroptosis by attenuating the expression of glutathione peroxidase 4 (GPX4) and nuclear erythroid 2-related factor 2 (Nrf2). DHA-treated PC3R cells produced ROS. The ROS and cytotoxicity were reversed by treatment with ferrostatin-1. DHA combined with docetaxel inhibited EMT by regulating the expression of E-cadhein and N-cadherin. In summary, DHA reversed drug resistance and induced cytoprotective autophagy and ferroptosis by regulating the PI3K/AKT/Nrf2/GPX4 signalling pathway in PC3R cells. We propose that DHA could be developed as a chemosensitizer and that the PI3K/AKT /Nrf2/GPX4 signalling pathway might be a promising therapeutic target for overcoming cancer drug resistance."[2] en.wikipedia.org/wiki/Docos...

[cesanon]

Welcome back. I have missed you.

[Scout4answers]

As always Patrick, another stimulating discussion. Just finished some smoked Salmon from Costco. Farm raised but oh so tasty... How can I find the DHA content?

[pjoshea13 in reply to Scout4answers]

I can't vouch for accuracy, but:

"A dinner portion of farmed salmon (150 grams) will provide an average of 1.8 grams of EPA and DHA. DHA accounts for well over half of this."

I try to get smoked salmon from Norway.

I will not buy salmon from Chile.

The "sashimi special" at a nearby restaurant always includes some salmon. Delicious, but I have no idea how they source it. If ordering à la carte, I would avoid salmon.

-Patrick

[treedown]

I also am glad your back. Hopefully your return will encourage others to do the same.

[MateoBeach]

I love it when you talk that way, Patrick. You’re speaking my language. 💕🙏

[Sunlight12]

I am so glad you mentioned the point about oil possibly being oxidized or rancid..it hooks into a concern I have with many food studies. The study says "fish oil" was tested or "olive oil", but little else. There is so much we that don't know: farm raised fish or wild? Organic olives or not? Cold pressed or not? Cold processed or not? Shipped and kept cold or not? Nitrogen-flushed, light-blocked bottles and sealed to protect from oxidation? I have to think there could be some significant differences in results between fish oil from wild-caught fish, cold-pressed and processed and etc, vs oil farm-raised fish, heated, in a non-light-block bottle etc.

-Sun

[cujoe]

Patrick - Does this say anything about the need to boost/reduce EPA? And am I correct in that Omega 3s are no longer the cursed enemy of PCa? Say it ain't so?

ncbi.nlm.nih.gov/pmc/articl...

[pjoshea13 in reply to cujoe]

Cujoe,

Even as late as two years ago, EPA was still getting bad press (the EPIC study):

"There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk." [1]

The increased risk for lethal PCa was small, but why was there any?

"Circulating eicosapentaenoic acid concentrations have been associated with a higher risk of total prostate cancer in a pooled analysis of prospective studies12 and dietary intake of eicosapentaenoic acid was associated with a higher risk of advanced and fatal prostate cancer in the NIH‐AARP study.36 However, results from the Health Professionals Follow‐Up Study showed that a higher intake of eicosapentaenoic acid was associated with a lower risk of total and advanced prostate cancer.32"

Would be nice to see which EPIC countries were responsible for the finding. The data was collected for every country between, & including, the Nordics down to Greece. I can't believe that the finding was consistent for all of them.

Also: "Dietary intakes of individual fatty acids were estimated using center‐specific validated dietary questionnaires at baseline and calibrated with 24‐h recalls." How was EPA estimated? Did the data include fish by species?

One other point. In the U.S. fish consumption is often of the low-EPA/DHA fried variety. The omega-6:omega-3 ratio might be quite high in such a meal, after including French fries. The ratio is important imo. I can't comment on Individual EPIC countries, except to say that PCa mortality is decreased as one travels south.

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[cujoe in reply to pjoshea13]

Patrick - Your north-to-south observation is that of one who knows how to look beyond the research "headlines". I'm just getting there and have a great example of "headline distortion" that I will link you to in a reply to another of your recent posts. Maybe later today/tonight - or tomorrow. Ciao - cujoe