32 replies to this topic

[CallMeLucky]

http://m.medicalxpre...y-leukemia.html

Fish oil may hold key to leukemia cure

09:50, Cancer

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The compound shown above is D12-PGJ2, which closely resembles delta-12-protaglandin J3, or D12-PGJ3, a compound that targeted and killed the stem cells of chronic myelogenous leukemia, or CML, in mice during experiments conducted by Penn State researchers. According to the American Cancer Society, about 5,150 new cases of CML are reported annually and approximately 270 people die from the disease each year. Credit: Sandeep Prabhu

A compound produced from fish oil that appears to target leukemia stem cells could lead to a cure for the disease, according to Penn State researchers. The compound -- delta-12-protaglandin J3, or D12-PGJ3 -- targeted and killed the stem cells of chronic myelogenous leukemia, or CML, in mice, said Sandeep Prabhu, associate professor of immunology and molecular toxicology in the Department of Veterinary and Medical Sciences. The compound is produced from EPA -- Eicosapentaenoic Acid -- an Omega-3 fatty acid found in fish and in fish oil, he said.

"Research in the past on fatty acids has shown the health benefits of fatty acids on cardiovascular system and brain development, particularly in infants, but we have shown that some metabolites of Omega-3 have the ability to selectively kill the leukemia-causing stem cells in mice," said Prabhu. "The important thing is that the mice were completely cured of leukemia with no relapse."

The researchers, who released their findings in the current issue of Blood, said the compound kills cancer-causing stem cells in the mice's spleen and bone marrow. Specifically, it activates a gene -- p53 -- in the leukemia stem cell that programs the cell's own death. "p53 is a tumor suppressor gene that regulates the response to DNA damage and maintains genomic stability," Prabhu said.

Killing the stem cells in leukemia, a cancer of the white blood cells, is important because stem cells can divide and produce more cancer cells, as well as create more stem cells, Prabhu said.

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Penn State researchers initially tested a compound produced from fish oil on a type of leukemia found in mice called the Friend Virus. This slide shows a Friend Virus Leukemia Stem Cell. Learning how to target and kill leukemia stem cells is critical to finding a cure for leukemia. Credit: Robert Paulson

The current therapy for CML extends the patient's life by keeping the number of leukemia cells low, but the drugs fail to completely cure the disease because they do not target leukemia stem cells, said Robert Paulson, associate professor of veterinary and biomedical sciences, who co-directed this research with Prabhu.

"The patients must take the drugs continuously," said Paulson. "If they stop, the disease relapses because the leukemia stem cells are resistant to the drugs."

Current treatments are unable to kill the leukemia stem cells, Paulson noted. "These stem cells can hide from the treatment, and a small population of stem cells give rise to more leukemia cells," said Paulson. "So, targeting the stem cells is essential if you want to cure leukemia."

During the experiments, the researchers injected each mouse with about 600 nanograms of D12-PGJ3 each day for a week. Tests showed that the mice were completely cured of the disease. The blood count was normal, and the spleen returned to normal size. The disease did not relapse.

In previous experiments, the compound also killed the stem cells of Friend Virus-induced leukemia, an experimental model for human leukemia.

The researchers focused on D12-PGJ3 because it killed the leukemia stem cells, but had the least number of side effects. The researchers currently are working to determine whether the compound can be used to treat the terminal stage of CML, referred to as Blast Crisis. There are currently no drugs available that can treat the disease when it progresses to this stage.

More information: Researchers have uncovered what cells respond to anesthesia in an organism known as the C. elegans, according to a new study from the Seattle Children's Research Institute.

Provided by Pennsylvania State University

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[PhilB]

Before the lawyers come and get you, I think we need to clarify what you're going to do with your fish oil when you get it.  If you're planning to try injecting it as they did with the mice it definitely can hurt!

Oily fish cooked with turmeric anyone?

[CallMeLucky]

I'm not holding my breath, we can add it to the list of other "potential" cures that seem to kill leukemia stem cells in a petri dish or a mouse.  I'm pretty sure I can kill a leukemia stem cell in a petri dish with some bleach.  The key is getting it to work in a human.  More  than anything I just get encouraged when I hear that people are looking at this stuff.  For a pretty rare disease, it gets a lot of attention, which means that hopefully someone will eventually stumble onto something that works.

[scuba]

Interesting ... I began taking Omega 3 fish oil to assist Curcumin in getting into my blood.  Fish oil is good to help Curcumin bio-availability.

How interesting it would be to have CML reduced dramatically or even cured because of the fish oil and not the curcumin + Sprycel?

But ... like you said, Gary, not holding my breath.  But since fish oil is good for you anyway - it doesn't hurt to make sure we keep taking it.

Any correlation with fish eaters and CML in the general population?  Japanese sure eat a lot of fish - do they have less CML significantly?

What about Norwegians?  They eat Herring - raw?  And Eskimo's in the Tundra? (never mind, they eat whale blubber).

[CallMeLucky]

There is a high incidence of CML in Asia, but I believe that is due to the radiation exposure during WWII, but who knows?

To clarify on the FISH oil, it is easy to read over an important piece of the story

"The compound shown above is D12-PGJ2, which closely resembles delta-12-protaglandin J3, or D12-PGJ3, a compound that targeted and killed the stem cells of chronic myelogenous leukemia, or CML, in mice during experiments conducted by Penn State researchers."

"The compound is produced from EPA -- Eicosapentaenoic Acid -- an Omega-3 fatty acid found in fish and in fish oil"

If I'm reading it right D12-PGJ2 is what is commonly found in fish oil - D12-PGJ3 is something they derived from the fish oil, which was able to kill the stem cell in the mouse.  Remember there is no profit in finding something that is already available, you have to tweak it just enough to patent it.

[scuba]

Good point.  Subtle.

Do we know if the metabolizing of Omega-3 fish oil creates this compound? (D12-PGJ3)

[scuba]

Also - in reference to your comment on "there is no profit in finding something that is already available ..."

Gordon Gekko: The point is ladies and gentlemen that greed, for lack of a better word, is good.

Greed is good - it leads to life saving TKI's which - until a cure is found - keeps us alive.  Without 'greed' for lack of a better word, there would be no Tyrosine Kinase inhibitor. 

[CallMeLucky]

Greed is a good motivator, so I don't have a problem with that, the point I was making is that it is a bit disheartening that a researcher could be on the path to something that might work, but if there is no profit in it, the research will most likely not be funded.  This is just the way the world works, no point in crying about it.  If all it takes is them tweaking something that already exists so they can make a buck on it, I'm fine with that, just get it done....

[scuba]

More info on your very interesting find, Gary: (the bold emphasis in the body of the abstract is mine).

Trey:  Would welcome your comments.  This does, in fact, look quite interesting.  Also - I sent a copy to Dr. Cortes and he responded that this is new. 

As RCT would say, however, "it's just mice".

{Delta}12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice.

Hegde S, Kaushal N, Ravindra KC, Chiaro C, Hafer KT, Gandhi UH, Thompson JT, Vanden Heuvel JP, Kennett MJ, Hankey P, Paulson RF, Prabhu KS.

Source

Ctr for Molecular Immunology & Infectious Disease and Ctr for Molecular Toxicology & Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.

Abstract

Targeting cancer stem cells (CSC) is of paramount importance to successfully combat the relapse of cancer. Recently, in silico screen of public gene expression datasets identified cyclooxygenase- derived cyclopentenone prostaglandins (CyPG) as likely agents to target malignant stem cells. We show here that ?(12)-PGJ(3), a novel and naturally produced CyPG from the dietary fish-oil omega-3 polyunsaturated fatty acid (n-3 PUFA), eicosapentaenoic acid (EPA; 20:5), alleviates the development of leukemia in two well-studied murine models of leukemia. Intraperitoneal administration of ?(12)-PGJ(3) to mice infected with Friend erythroleukemia virus (FV) or those expressing chronic myelogenous leukemia (CML) oncoprotein BCR-ABL in the hematopoietic stem cell (HSC) pool completely restored normal hematological parameters, splenic histology, and enhanced the survival of such mice. More importantly, ?(12)-PGJ(3) selectively targeted leukemia stem cells (LSC) for apoptosis in the spleen and bone marrow. This treatment completely eradicated leukemia stem cells in vivo as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplants. Given the potency of n-3 PUFA-derived CyPG and the well-known refractoriness of LSC to currently used clinical agents, ?(12)-PGJ(3) may represent a new chemotherapeutic for leukemia that targets LSCs.

[Trey]

Fish oil is a close relative of snake oil. 

[CallMeLucky]

I have to go revise my letter to Santa.

[GerryL]

Have to agree with you a little bit there Trey - I have been taking fish oil for at least 10 years, didn't prevent the CML.

Am hoping it will keep Alzheimer away though - when I mentioned I was taking it to the GP, he asked me if it was working. I told him if I was still able to keep my appointments with him when I got into my 90s we would know it was working.

[Happycat]

Lucky,

I'm so proud of you for cottoning on to the  derivative!  Warms my chemist's heart. 

Regarding mouse vs. human, mouse models do not predict drug activity in humans all that well.  Rats are better. 

Traci

[Trey]

If you look closely at the picture of the fish oil compound you will note why this cannot possibly work:

[scuba]

Trey - Bravo!

Merry Christmas!

[hannibellemo]

Waiter, there appears to be a feather in my fish!

[cousineg]

                  Will freedom from CML come from the sea?

[Judy2]

I don't know but that picture makes me want to take a cruise!!!

Judy

[Dina]

So should we start taking the fish oil, it wont hurt, right??

I got two big jars, hope its safe with the Tasigna.

[CallMeLucky]

Always check with your doctor or pharmacist before taking anything with your Tasigna.

Keep in mind that the article does not say Fish Oil will do anything for CML.  They are talking about a compound they derived from Fish Oil.  Fish Oil in its natural state does not do anything particular for CML.

In general, Fish Oil is healthy for you so if your doctor says it is ok to take it, then go ahead, but I don't think anyone should have any expectations when taking it regarding CML stem cells.