Arachidonic Acid and Cancer. (X-Factor)

Bigfishy

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I stumbled over a few things which led me to do some research on a few other thing which... well figure it out for yourself.


Arachidonic acid activation of translation initiation signaling in vascular smooth muscle cells.

Neeli I, Yellaturu CR, Rao GN.

Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

To understand the role of arachidonic acid (AA) in regulating vascular smooth muscle cell (VSMC) growth, its effects on phosphorylation of Akt, S6K1, ribosomal protein S6, 4EBP1, and eIF4E were studied. Arachidonic acid stimulated phosphorylation of Akt, S6K1, ribosomal protein S6, 4EBP1, and eIF4E in a time-dependent manner in VSMC. Arachidonic acid stimulation of phosphorylation of the above signaling molecules is specific, as these events were not affected by other unsaturated or saturated fatty acids. Metabolic conversion of AA via the LOX/MOX and/or COX pathways, to some extent, was required for its effects on the phosphorylation of Akt, S6K1, ribosomal protein S6, 4EBP1, and eIF4E. In addition, AA increased PI3K activity in a time-dependent manner in VSMC. LY294002, an inhibitor of PI3K, completely blocked AA-induced phosphorylation of Akt, S6K1, ribosomal protein S6, 4EBP1, and eIF4E, suggesting a role for PI3K in these effects. Consistent with its effects on translation initiation signaling events, AA induced global protein synthesis in VSMC and this response was dependent, to some extent, on its metabolism via the LOX/MOX and/or COX pathways, and mediated by the PI3K/Akt/mTOR pathway. Thus, the above observations provide the first biochemical evidence for the role of AA in the activation of translation initiation signaling in VSMC.


Genistein-induced apoptosis via Akt signaling pathway in anaplastic large-cell lymphoma.

Park SS, Kim YN, Jeon YK, Kim YA, Kim JE, Kim H, Kim CW.

Department of Pathology and Tumor Immunity, Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-779, Korea, [email protected].

More than half of anaplastic large-cell lymphoma (ALCL) are associated with chromosomal translocation t(2;5)(p23;q35) that leads to the expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncoprotein. NPM-ALK activates the antiapoptotic phosphatidylinositol-3 kinase/Akt (PI3K/Akt) signaling pathway, which plays a critical role in cell survival and apoptosis. Inhibition of the PI3K/Akt pathway has been considered as a therapeutic target for cancer where PI3K/Akt activation is a causative factor. Genistein, a natural isoflavonoid found in soy products, has been shown to inhibit cell growth and induce apoptosis in a wide variety of cell lines. Here, we demonstrated that treatment of two t(2;5) ALCL cell lines, SUDHL-1 and Karpas299, with genistein induced apoptosis in a time- and dose-dependent manner. Concurrently, these cells exhibited a decrease in Akt protein levels and subsequent downregulation of Akt activity (Akt phosphorylation). Furthermore, genistein treatment induced mitochondrial membrane potential change, caspase-3 activation and PARP cleavage. From these results, we conclude that inhibition of the Akt signaling pathway and induction of apoptosis by genistein could be used as a new treatment modality for the prevention and/or treatment of t(2;5) ALCL and other hematopoietic malignancies.

PMID: 15883821 [PubMed - as supplied by publisher]






So it would seem that arachidonic acid not only makes muscles grow (for some people) but cancer as well. I was extremely interested in this product as a PCT aid but... I think I may just take a pass on this one.
 

cubical

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you cant take any EFAs while taking xfactor or milk thistle. no way im taking this supp
 

w_llewellyn

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* There are a number of long-term macro studies looking at EFAs and cancer, and none of them show a correlation between AA and risk. They show no correlation. PGs, as potent growth promoting hormones, can help cancer grow if you have it, just like GH, Testosterone, IGF-1, and estrogens. But AA is not the direct cause.

* OTHER Omega 6 acids are proven to increase cancer risk, like LA, which we eat ample amounts of in the U.S.

* AA is added to baby forumla in many countries, U.S. included, to help infant growth.

* AA has been granted self-declaired G.R.A.S. status by the FDA, which means Generally Regarded As Safe. The manufacturer has been approved the claim that it is safe, which is not common for a supplement product. Ample data is being evaluated for a formal adoption of this claim.

* Numerous clinical studies have investigated the use of AA as we have outlined, and ALL have concluded the nutrient SAFE to use.

Bottom line: This is an essential fatty acid, not a drug or carcinogenic chemical. The subject of AA, immune response, inflammation etc. is HUGE, and easy to get confused or lost in when floating around pub med..

I just hope some of you who don't want to bother looking at all the various studies understand that this product was only brought out by use after a long investigation into its safety. It is indeed FAR safer than prohormones.
 

w_llewellyn

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you cant take any EFAs while taking xfactor or milk thistle. no way im taking this supp
You can take them.. They just stop X-Factor from working..
 
Par Deus

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Some other things that activate PI3K:

glucose, insulin, leucine, IP6
 

Bigfishy

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I don't mean to screw anybody and I welcome your opposing views, and I actually am hopeful that AA is safe as I have read plenty of good reviews on it and have a couple bottles in my personal supplement stash. I also believe that it is important the the consumer understands the possible risks involved. I planned on using AA until I found out that the pain I've had in my ankle for the past 3 years are bone tumors (Im 21 years old). This along with the below excerpt* lead me to do more research on AA and tumors. From what I understand AA makes tumors grow kinda like IGF-1 and GH. All I have to say is thank god I found this out before supplementing AA as my ankle barely funtions with the tumors the size they are. I just really wish that this information had been more easily avaliable.

I again stress first that I have no motive other than my safety and the safety of my bodybuilding peers. Second I am 100% open to being wrong. Im looking for the truth not excuses to hurt anybody in the business.


*I know its not a scientific document so flame as needed

http://www.imagination-institute.com/The%20Cancer%20Diet.htm

"Unlike heart disease, in which both good and bad eicosanoids play a role, cancer appears to be the result of a runaway production of bad eicosanoids. So the goal in treating and preventing cancer is to clamp down on the synthesis of bad eicosanoids by choking off the supply of arachidonic acid."
Arachidonic acid is the building block of bad eicosanoids. It is found in the fatty tissue of muscle meat and organ meat. Just as high insulin levels in humans produce high levels of arachidonic acid in our bodies, animals fattened on grain have high levels of arachidonic acid in their fat and organs.
 
lifted

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you cant take any EFAs while taking xfactor or milk thistle. no way im taking this supp
WHAT??? Where did you hear you can't take EFA's and milk thistle together?? And what is the reasoning??
 

Bigfishy

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Hey Par your my idol, but I believe that IP6 actually inhibits PI3k. Could this be used in conjunction with AA to counteract increased PI3K activity without hurting the effectivness of the product? Yet again, I'm just a curious kid and I leave the real interpretion and application of this stuff to the the pros.

Impairment of erbB1 receptor and fluid-phase endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate carcinoma DU145 cells.

Zi X, Singh RP, Agarwal R.


Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA.

Recently, we observed that epidermal growth factor receptor (EGFR or erbB1) endocytosis and associated mitogenic signaling occur in human prostate cancer (PCA) cells, suggesting that erbB1 endocytosis might be involved in advanced and androgen-independent PCA growth. Based on these findings, and the fact that aberrant expression of erbB family members is common in human prostatic intraepithelial neoplasia and invasive PCA, we reasoned that impairment of erbB1 endocytosis and associated mitogenic signaling might inhibit PCA growth. Inositol hexaphosphate (IP6) interacts with plasma membrane clathrin-associated protein complex 2 (AP2) and inhibits phosphatidylinositol 3-kinase (PI3K). As these are essential components of receptor-mediated and fluid-phase endocytosis, respectively, we reasoned that IP6 might impair erbB1 endocytosis and associated signaling in human PCA cells, leading to their growth inhibition. IP6 strongly to completely inhibited (26-100%; P < 0.05) transforming growth factor alpha-induced binding of activated erbB1 to AP2 in human PCA DU145 cells, demonstrating the impairment of the initial step in ligand-induced erbB1 endocytosis. IP6 treatment of cells resulted in a dose-dependent increase (1.8- to 7. 7-fold compared with cells treated with ligand alone; P < 0.05) in levels of activated erbB1. These two findings suggest that the inhibitory effect of IP6 on receptor endocytosis is independent of its lack of effect on ligand-induced erbB1 activation. These effects of IP6, however, were associated with strong inhibition of ligand-induced Shc phosphorylation (77-84% decrease; P < 0.05) and its binding to erbB1 (58-100% decrease; P < 0.05). IP6 also significantly and dose-dependently inhibited fluid-phase endocytosis (19-52%; P < 0.05). It inhibited PI3K-AKT signaling pathway as an upstream response in its effect on the inhibition of fluid-phase endocytosis. The inhibition of erbB1 receptor and fluid-phase endocytosis, and associated signaling by IP6, was corroborated by very strong to complete inhibition (70-100%; P < 0.05) of extracellular signal-regulated protein kinase 1/2 activation by IP6. IP6 significantly (P < 0.05) inhibited anchorage-dependent and -independent inhibition (50-100% and 30-75%, respectively) in DU145 cells. Targeting the impairment of erbB1 endocytosis and associated mitogenic signaling by IP6 in advanced and androgen-independent human PCA DU145 cells could be a useful approach for treating PCA.

PMID: 11133812 [PubMed - indexed for MEDLINE]
 
CyberMuscle

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WHAT??? Where did you hear you can't take EFA's and milk thistle together?? And what is the reasoning??
I beleive he was talking about while you are using x-factor. I know you cant use EFAs with X-factor because EFA are anti-inflammatory and x-factor is a pro-inflammatory. I dont know why you couldnt take milk thistle, i didnt know it had an anti-inflammatory effect.
 

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The whole Zone Diet centers around having the proper ratio of EPA to arachidonic acid so the body will then have balance between "good" and "bad" eicosanoids. If one's body is out of balance and has a ratio of "good" to "bad" eicosanoids that highly favors the "bad" eicosanoids, then Dr. Sears claims they are in a state of cellular inflammation. According to Sears, cellular inflammation is the cause of most chronic disease, it makes us mentally "slower", and many other unsettling things etc. What is everyone's take on his work.
 

w_llewellyn

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The whole Zone Diet centers around having the proper ratio of EPA to arachidonic acid so the body will then have balance between "good" and "bad" eicosanoids. If one's body is out of balance and has a ratio of "good" to "bad" eicosanoids that highly favors the "bad" eicosanoids, then Dr. Sears claims they are in a state of cellular inflammation. According to Sears, cellular inflammation is the cause of most chronic disease, it makes us mentally "slower", and many other unsettling things etc. What is everyone's take on his work.
The put it all in perspective, these are the exact criticisms of the Atkins Diet (too much red meat, too much Arachidonic acid, too much inflammation). This makes sense as Atkins can cause very sharp increases in AA levels due to the high fat/meat intake. X-Factor probably wouldn't be healthy to do forever, just like Atkins wouldn't. But short term I think we all know how the dangers of Atkins diet are overblown, especially when healthy bodybuilders are doing it.
 

w_llewellyn

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Some other things that activate PI3K:

glucose, insulin, leucine, IP6
Oh, don't forget the big one - IGF-1. IGF-1 mediates its effects on protein synthesis/glucose transport via PI3K.
 

Grant

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I tried it for about 1 bottle, I had three bought, but I retured all 3, ( 2 and a bottle with a few caps left)when I used it perfectly (2+2+1, no efa's, ate more red meat, haha no sushi!!! no fish, no NAC) and got nothing from it, MAYBE a pump is all, no signifigant increases in lifts, no increased soreness at all, no gain above what I normally get. Maybe I am missing out on something??? Its to late to try it again, but I just wanna know am I forgetting something?
 
Aeternitatis

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So it would seem that arachidonic acid not only makes muscles grow (for some people) but cancer as well. I was extremely interested in this product as a PCT aid but... I think I may just take a pass on this one.
That's a funny statement considering steroids can make cancers grow as well but that didn't stop you.
 

w_llewellyn

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I tried it for about 1 bottle, I had three bought, but I retured all 3, ( 2 and a bottle with a few caps left)when I used it perfectly (2+2+1, no efa's, ate more red meat, haha no sushi!!! no fish, no NAC) and got nothing from it, MAYBE a pump is all, no signifigant increases in lifts, no increased soreness at all, no gain above what I normally get. Maybe I am missing out on something??? Its to late to try it again, but I just wanna know am I forgetting something?
This is the reason we decided to change the forumulation towards a higher dose/cap count. Most people really haven't been on it long enough to jugde its efficacy on 1 bottle. It requires a bit of loading before it kicks in. You probably were just starting to notice it kicking in (pumps) when you stopped.

If you want to try it again, please email us at "sales at molecularnutrition.net" (make it sales@). We'll arrange to replace the bottle you lost, but ya have to promise to go on it for 3-4 weeks this time (1 full NEW bottle) before passing judgement.. ;)
 
TheUnlikelyToad

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If you want to try it again, please email us at "sales at molecularnutrition.net" (make it sales@). We'll arrange to replace the bottle you lost, but ya have to promise to go on it for 3-4 weeks this time (1 full NEW bottle) before passing judgement.. ;)

That's crap Bill.

I'm doin a X-factor log at semi-low doses just for you and I never got an offer like that... I call favorites :rasp:
 

Bigfishy

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That's a funny statement considering steroids can make cancers grow as well but that didn't stop you.
It is true that test can make androgen dependant cancers such as prostate cancer grow. Other than that i haven't found and proof that it has any effect on any other types of cancer. Esspecially with the osteo ostoma (my tumors) I have found no correlation between them and test and growth. Yet again if anybody has info that I missed please share it with me as my heal comes before my pride (not true). Also I suggest that unless you have something construtive and relevant to say keep it to yourself. Im trying to pose questions about products for the good of everyone at AM, no need to flame. I've had the tumors removed two days ago (**** OUCH) they suck, largest osteo ostoma doctor has every seen. Lastly I agree that AA may well be safe in moderation. Like I said im not here to bring people down but simple to pose questions that i see as relevant and important. When my surgery heals I might just give X-Factor a spin and see what all the hoopla is about.



Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro. Distribution of peripheral blood T lymphocytes and cell cycle progression.

Aboudkhil S, Henry L, Zaid A, Bureau JP.


Departement of Biology, UFR Environment and Health, Faculty of Science and Technique University Hassan II, Mohammedia, Maroc. [email protected].

In transplanted mice, the P388 tumor grew better in castrated than in non castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small tumor tissue (<10 mg). The correlation observed between the tumor weight and T cell subset in PBL and in the mice with small tumors could confirm the important intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone (DT) injection reduced strongly weight and tumor growth in mice. On top of that, DT administration induced a significant increase in the percentage of blood CD8+ cells in grafted mice. The effect of DT was studied on the cell cycle progression, in tumor tissue of P388 tumor bearing BDF1 mice and in P388 murine leukemia cell line in culture. The cell cycle analysis in tumor tissue showed that DT decreased both the cells in S phase and the proliferating leukemic cells, with accumulation of cells in G0/G1 phase. The testosterone can inhibit the proliferation of leukemic cells with a pharmacological dose (10exp-7 M). This growth inhibition, dose and time dependent, was associated with cell cycle arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation between tumor weight and the percentage of cells in G0/G1 and the relative number of cells in proliferative state (S + G2/M). To conclude, our experiments reported that testosterone prevents the growth of tumor: indirectly by modulation of subsets T cells distribution and directly by the alteration of the cell cycle.

PMID: 15875090 [PubMed - in process]
 

w_llewellyn

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It is true that test can make androgen dependant cancers such as prostate cancer grow. Other than that i haven't found and proof that it has any effect on any other types of cancer. Esspecially with the osteo ostoma (my tumors) I have found no correlation between them and test and growth. Yet again if anybody has info that I missed please share it with me as my heal comes before my pride (not true). Also I suggest that unless you have something construtive and relevant to say keep it to yourself. Im trying to pose questions about products for the good of everyone at AM, no need to flame. I've had the tumors removed two days ago (**** OUCH) they suck, largest osteo ostoma doctor has every seen. Lastly I agree that AA may well be safe in moderation. Like I said im not here to bring people down but simple to pose questions that i see as relevant and important. When my surgery heals I might just give X-Factor a spin and see what all the hoopla is about.



Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro. Distribution of peripheral blood T lymphocytes and cell cycle progression.

Aboudkhil S, Henry L, Zaid A, Bureau JP.


Departement of Biology, UFR Environment and Health, Faculty of Science and Technique University Hassan II, Mohammedia, Maroc. [email protected].

In transplanted mice, the P388 tumor grew better in castrated than in non castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small tumor tissue (<10 mg). The correlation observed between the tumor weight and T cell subset in PBL and in the mice with small tumors could confirm the important intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone (DT) injection reduced strongly weight and tumor growth in mice. On top of that, DT administration induced a significant increase in the percentage of blood CD8+ cells in grafted mice. The effect of DT was studied on the cell cycle progression, in tumor tissue of P388 tumor bearing BDF1 mice and in P388 murine leukemia cell line in culture. The cell cycle analysis in tumor tissue showed that DT decreased both the cells in S phase and the proliferating leukemic cells, with accumulation of cells in G0/G1 phase. The testosterone can inhibit the proliferation of leukemic cells with a pharmacological dose (10exp-7 M). This growth inhibition, dose and time dependent, was associated with cell cycle arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation between tumor weight and the percentage of cells in G0/G1 and the relative number of cells in proliferative state (S + G2/M). To conclude, our experiments reported that testosterone prevents the growth of tumor: indirectly by modulation of subsets T cells distribution and directly by the alteration of the cell cycle.

PMID: 15875090 [PubMed - in process]
It is all about the tissue. Androgen responsive tissues tend to produce very androgen responsive cancers (loose rule). Take GH/IGF-1 for example. Most cells are responsive to these hormones, so anything that increases GH, IGF-1, or signalling of either could also help a variety of cancers increase in mass.

If you have cancer, or ever are someone with a strong genetic/familial predisposition for it, and you want to play it safe, I would not advise taking any anabolic substances.
 

w_llewellyn

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That's crap Bill.

I'm doin a X-factor log at semi-low doses just for you and I never got an offer like that... I call favorites :rasp:
I only give out to free bottles to people that take manly doses.

:)
 
TheUnlikelyToad

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Oh my... I'll remember that Bill when I give my 'honest' review. ;)
 
GuyverX

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a small plea

* There are a number of long-term macro studies looking at EFAs and cancer, and none of them show a correlation between AA and risk. They show no correlation. PGs, as potent growth promoting hormones, can help cancer grow if you have it, just like GH, Testosterone, IGF-1, and estrogens. But AA is not the direct cause.

* OTHER Omega 6 acids are proven to increase cancer risk, like LA, which we eat ample amounts of in the U.S.

* AA is added to baby forumla in many countries, U.S. included, to help infant growth.

* AA has been granted self-declaired G.R.A.S. status by the FDA, which means Generally Regarded As Safe. The manufacturer has been approved the claim that it is safe, which is not common for a supplement product. Ample data is being evaluated for a formal adoption of this claim.

* Numerous clinical studies have investigated the use of AA as we have outlined, and ALL have concluded the nutrient SAFE to use.

Bottom line: This is an essential fatty acid, not a drug or carcinogenic chemical. The subject of AA, immune response, inflammation etc. is HUGE, and easy to get confused or lost in when floating around pub med..

I just hope some of you who don't want to bother looking at all the various studies understand that this product was only brought out by use after a long investigation into its safety. It is indeed FAR safer than prohormones.
I did a read up on several sites about AA. I bought the syntrax version( took for 10 days) first then after I read about your X-Factor being the original I bought a bottle of X-Factor. It gives me a good deep sleep(I work graveyard shift and could never sleep over 4 hours in the day-- now its 9 straight) and has improved my strength and mood at 1000mg/4caps a day. when I finish 50 days I am going to pop in my Fish oil supplements. and I have only been taking it for a couple of days. (I have a high response to any supplement for some reason... even vitamins).

I want to ask would you consider bringing out an Ecdy supplement as well at the same mg as your X-Factor AA supplement?
Your AA stacked with ecdy seems to be the best stack I've ever tried. And I can eat way more calories and still can stay rather hard and ripped.

Thumbs up for X-Factor.....
 
GuyverX

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Try taking it with some Omega 6...
btw Guyver? I used to be into that a while back, cool stuff.
Thanks for the advice man..
Lolz.... p.s. you guys have excellent products too
 
Aeternitatis

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when I finish 50 days I am going to pop in my Fish oil supplements.
Just a warning: there's no need to OD on the fish oil. It's not like you suddenly need PCT or something like that after X-factor. Yes, adding fish oil to your diet will be a good thing after the cycle, just don't go crazy with it. I personally would not go above 2-3 grams of fish oil per day (thats regular, non-concentrated).

Just be sure to get a wide variety of fatty acids. The proper ratio is more important than anything else.
 

Grant

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This is the reason we decided to change the forumulation towards a higher dose/cap count. Most people really haven't been on it long enough to jugde its efficacy on 1 bottle. It requires a bit of loading before it kicks in. You probably were just starting to notice it kicking in (pumps) when you stopped.

If you want to try it again, please email us at "sales at molecularnutrition.net" (make it sales@). We'll arrange to replace the bottle you lost, but ya have to promise to go on it for 3-4 weeks this time (1 full NEW bottle) before passing judgement.. ;)


Awwww man, I never saw where he offered a free bottle to try it at a better dose... haha is 2 years a a few months too late to take you up on the offer?

I had to bump this thread, was reading about AA and noticed I got offered to try the stuff :(
 

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