460 replies to this topic

[thefirstimmortal]

Just glad you got it!

Yeah, me too. Of all people to have a glitch.

Edited by thefirstimmortal, 14 August 2008 - 04:23 AM.

[thefirstimmortal]

http://www.imminst.o...&...st&p=257080

[thefirstimmortal]

The aminoacid glycine works against angiogenesis, glycine is not expensive, it can not inhibit the formation of new tumors but it inhibits and limits the growth of already existing. (1)

I have logged your post and glycine in my research data base. Thank You aidanpryde.

[thefirstimmortal]

Good night Missminni

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[thefirstimmortal]

Good morning Missminni

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[missminni]

Good morning Missminni

Good morning. Hope all goes well today.

[jCole]

Good morning Missminni

Good morning. Hope all goes well today.

As do I!

Mid month bro!

[sgreory]

If you want to get your body more alkeline instead of acidic, I suggest apple cider vinegar. It is also very helpful for a a lot of other things.

[jCole]

If you want to get your body more alkeline instead of acidic, I suggest apple cider vinegar. It is also very helpful for a a lot of other things.

Great for your skin... I've never had acne problems, but when I started weight training hard this past year, I broke out like no other. But a couple tablespoons of Apple Cider Vinegar before bed cleared that right up!

[thefirstimmortal]

If you want to get your body more alkeline instead of acidic, I suggest apple cider vinegar. It is also very helpful for a a lot of other things.

MissMinni recomended this to me a while ago. What are the deitary uses of it? I'm not real fond of vinegar, how can it be used in the diet? Do you have to drink it?

[missminni]

If you want to get your body more alkeline instead of acidic, I suggest apple cider vinegar. It is also very helpful for a a lot of other things.

MissMinni recomended this to me a while ago. What are the deitary uses of it? I'm not real fond of vinegar, how can it be used in the diet? Do you have to drink it?

You can take a tablespoon of Braggs apple cider vinegar in a glass of water or sprinkle it on a salad as a dressing.

Edited by missminni, 16 August 2008 - 07:11 AM.

[jCole]

If you want to get your body more alkeline instead of acidic, I suggest apple cider vinegar. It is also very helpful for a a lot of other things.

MissMinni recomended this to me a while ago. What are the deitary uses of it? I'm not real fond of vinegar, how can it be used in the diet? Do you have to drink it?

You can take a tablespoon of Braggs apple cider vinegar in a glass of water or sprinkle it on a salad as a dressing.

I mix it in my protein drink, then dash in a few drops of Stevia, which helps dull the bitterness a bit.

[missminni]

I just read this in wikipedia, certainly not the last word, but worth noting.

Resveratrol given orally also had no effect on leukemia and lung cancer;[12][17] however, injected intraperitoneally, 2.5 or 10 mg/kg of resveratrol slowed the growth of metastatic Lewis lung carcinomas in mice.[12][18] Resveratrol (1 mg/kg orally) reduced the number and size of the esophageal tumors in rats treated with a carcinogen.[19] In several studies, small doses (0.02-8 mg/kg) of resveratrol, given prophylactically, reduced or prevented the development of intestinal and colon tumors in rats given different carcinogens.[12]

The fact that they used 1mg/kg orally and reduced tumor size and TFI is using 250mg/kg leads me to believe he's got that covered.
As for the lung cancer, I would hope the huge amount he is taking orally would have an affect. Intraperitonel (abdominal cavity) injection seems
like a long shot considering the doctor he is working with, but the study where the 70 year old man used 15g a day of fish oil/EPA/DHA and
cured himself of lung cancer came to mind. I think that should be pursued vigorously as well. 15 grams of fish oil a day is not that difficult to achieve.

[davidd]

Emodin a good thing?

http://lib.bioinfo.pl/pmid:17935676

Chin Med J (Engl). 2007 Oct 5;120 (19):1710-5 17935676 (P,S,E,B) Effects of emodin on gene expression profile in small cell lung cancer NCI-H446 cells. Zhong-Yan Fu, Jin-Xiang Han, Hai-Yan Huang BACKGROUND: The treatment of patients with small cell lung cancer (SCLC) is based on chemotherapy. However, the treatment is limited by the development of drug resistance. Emodin has been shown to exhibit an anti-cancer effect. But the molecular mechanism remains unclear. This study was conducted to investigate the effect of emodin on the gene expression profile changes in SCLC NCI-H446 cells. METHODS: NCI-H446 cells were treated with emodin and cell viability was determined by MTT assay. Cell apoptosis was determined by both flow cytometry and caspase-3 activity assay. The effect of emodin on the gene expression profile of NCI-H446 cells was analyzed using cDNA microarray. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to validate the microarray results. RESULTS: Emodin suppressed viability, induced apoptosis and changed cell cycle of NCI-H446 cells. Among the 1262 genes, 10 genes were up-regulated and 8 genes were down-regulated more than 2 folds in NCI-H446 cells when compared with the control cells after treatment with emodin for 12 hours, while 12 genes were up-regulated and 24 genes were down-regulated after treatment with emodin for 24 hours. These genes were involved in metabolism, signal transduction, transcription regulation, cytoskeleton organization, immune response, transport, protein synthesis, cell cycle control, cell adhesion and RNA processing. The RT-PCR results were consistent with those obtained by the microarray. CONCLUSIONS: Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.

I included the above URL as part of a very long post in another topic (http://www.imminst.o...&...st&p=258905), but figured this particular point may be valuable to post here. I apologize if it has been covered before.

I've since found these other references to emodin and lung cancer:

http://www.ncbi.nlm....pubmed/15941563


Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway.
Su YT, Chang HL, Shyue SK, Hsu SL.Institute of Medical Science, China Medical University, Taichung, Taiwan, ROC.

Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. In this study, we show that treatment with 50 microM emodin resulted in a pronounced release of cytochrome c, activation of caspase-2, -3, and -9, and apoptosis in human lung adenocarcinoma A549 cells. These events were accompanied by the inactivation of ERK and AKT, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential ((Delta)psi(m)), decrease of mitochondrial Bcl-2, and increase of mitochondrial Bax content. Ectopic expression of Bcl-2, or treatment with aurintricarboxylic acid, furosemide or caspase inhibitors markedly blocked emodin-induced apoptosis. Conversely, pharmacologic ERK and AKT inhibition promoted emodin-induced apoptosis. Furthermore, the free radical scavenger ascorbic acid and N-acetylcysteine attenuated emodin-mediated ROS production, ERK and AKT inactivation, mitochondrial dysfunction, Bcl-2/Bax modulation, and apoptosis. Take together, these findings suggest that in A549 cells [the lung cancer cells], emodin-mediated oxidative injury acts as an early and upstream change in the cell death cascade to antagonize cytoprotective ERK and AKT signaling, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, mitochondrial cytochrome c release, caspase activation, and consequent leading to apoptosis.

This one discusses many polyphenols (including resveratrol and emodin):

http://www.ncbi.nlm....;indexed=google


Chemosensitization and radiosensitization of tumors by plant polyphenols.
Garg AK, Buchholz TA, Aggarwal BB.Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

The treatment of cancer with chemotherapeutic agents and radiation has two major problems: time-dependent development of tumor resistance to therapy (chemoresistance and radioresistance) and nonspecific toxicity toward normal cells. Many plant-derived polyphenols have been studied intently for their potential chemopreventive properties and are pharmacologically safe. These compounds include genistein, curcumin, resveratrol, silymarin, caffeic acid phenethyl ester, flavopiridol, emodin, green tea polyphenols, piperine, oleandrin, ursolic acid, and betulinic acid. Recent research has suggested that these plant polyphenols might be used to sensitize tumor cells to chemotherapeutic agents and radiation therapy by inhibiting pathways that lead to treatment resistance. These agents have also been found to be protective from therapy-associated toxicities. How these polyphenols protect normal cells and sensitize tumor cells to treatment is discussed in this review. Antioxid. Redox Signal. 7, 1630-1647.



And lastly, they are working on improving Emodin's anti-cancer properties:

http://www.level1diet.com/645582_id

Synthesis, DNA binding and cytotoxicity of new pyrazole emodin derivatives.

A series of new anthrapyrazoles were derived from emodin by attaching various cationic alkyl amino side chains onto a pyrazole ring which had been incorporated into the anthraquinone chromophore. Compared with emodin, the derivatives had significantly higher DNA binding affinity based on interaction with calf thymus DNA, and much more potent cytotoxicity against different tumor cells. The derivatives with a mono-cationic alkyl side chain exhibited the highest DNA binding affinity and cytotoxicity. Publication Types: Research Support, Non-U.S. Gov't

Authored by Tan JH, Zhang QX, Huang ZS, Chen Y, Wang XD, Gu LQ, Wu JY. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, China.

Published in Eur J Med Chem. 2006 Sep;41(9):1041-7. Epub 2006 May 22. The full report is available online. A subscription to the periodical may be required.




David

[missminni]

Emodin a good thing?

http://lib.bioinfo.pl/pmid:17935676

Chin Med J (Engl). 2007 Oct 5;120 (19):1710-5 17935676 (P,S,E,B) Effects of emodin on gene expression profile in small cell lung cancer NCI-H446 cells. Zhong-Yan Fu, Jin-Xiang Han, Hai-Yan Huang BACKGROUND: The treatment of patients with small cell lung cancer (SCLC) is based on chemotherapy. However, the treatment is limited by the development of drug resistance. Emodin has been shown to exhibit an anti-cancer effect. But the molecular mechanism remains unclear. This study was conducted to investigate the effect of emodin on the gene expression profile changes in SCLC NCI-H446 cells. METHODS: NCI-H446 cells were treated with emodin and cell viability was determined by MTT assay. Cell apoptosis was determined by both flow cytometry and caspase-3 activity assay. The effect of emodin on the gene expression profile of NCI-H446 cells was analyzed using cDNA microarray. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to validate the microarray results. RESULTS: Emodin suppressed viability, induced apoptosis and changed cell cycle of NCI-H446 cells. Among the 1262 genes, 10 genes were up-regulated and 8 genes were down-regulated more than 2 folds in NCI-H446 cells when compared with the control cells after treatment with emodin for 12 hours, while 12 genes were up-regulated and 24 genes were down-regulated after treatment with emodin for 24 hours. These genes were involved in metabolism, signal transduction, transcription regulation, cytoskeleton organization, immune response, transport, protein synthesis, cell cycle control, cell adhesion and RNA processing. The RT-PCR results were consistent with those obtained by the microarray. CONCLUSIONS: Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.

I included the above URL as part of a very long post in another topic (http://www.imminst.o...&...st&p=258905), but figured this particular point may be valuable to post here. I apologize if it has been covered before.

I've since found these other references to emodin and lung cancer:

http://www.ncbi.nlm....pubmed/15941563


Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway.
Su YT, Chang HL, Shyue SK, Hsu SL.Institute of Medical Science, China Medical University, Taichung, Taiwan, ROC.

Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. In this study, we show that treatment with 50 microM emodin resulted in a pronounced release of cytochrome c, activation of caspase-2, -3, and -9, and apoptosis in human lung adenocarcinoma A549 cells. These events were accompanied by the inactivation of ERK and AKT, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential ((Delta)psi(m)), decrease of mitochondrial Bcl-2, and increase of mitochondrial Bax content. Ectopic expression of Bcl-2, or treatment with aurintricarboxylic acid, furosemide or caspase inhibitors markedly blocked emodin-induced apoptosis. Conversely, pharmacologic ERK and AKT inhibition promoted emodin-induced apoptosis. Furthermore, the free radical scavenger ascorbic acid and N-acetylcysteine attenuated emodin-mediated ROS production, ERK and AKT inactivation, mitochondrial dysfunction, Bcl-2/Bax modulation, and apoptosis. Take together, these findings suggest that in A549 cells [the lung cancer cells], emodin-mediated oxidative injury acts as an early and upstream change in the cell death cascade to antagonize cytoprotective ERK and AKT signaling, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, mitochondrial cytochrome c release, caspase activation, and consequent leading to apoptosis.

This one discusses many polyphenols (including resveratrol and emodin):

http://www.ncbi.nlm....;indexed=google


Chemosensitization and radiosensitization of tumors by plant polyphenols.
Garg AK, Buchholz TA, Aggarwal BB.Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

The treatment of cancer with chemotherapeutic agents and radiation has two major problems: time-dependent development of tumor resistance to therapy (chemoresistance and radioresistance) and nonspecific toxicity toward normal cells. Many plant-derived polyphenols have been studied intently for their potential chemopreventive properties and are pharmacologically safe. These compounds include genistein, curcumin, resveratrol, silymarin, caffeic acid phenethyl ester, flavopiridol, emodin, green tea polyphenols, piperine, oleandrin, ursolic acid, and betulinic acid. Recent research has suggested that these plant polyphenols might be used to sensitize tumor cells to chemotherapeutic agents and radiation therapy by inhibiting pathways that lead to treatment resistance. These agents have also been found to be protective from therapy-associated toxicities. How these polyphenols protect normal cells and sensitize tumor cells to treatment is discussed in this review. Antioxid. Redox Signal. 7, 1630-1647.



And lastly, they are working on improving Emodin's anti-cancer properties:

http://www.level1diet.com/645582_id

Synthesis, DNA binding and cytotoxicity of new pyrazole emodin derivatives.

A series of new anthrapyrazoles were derived from emodin by attaching various cationic alkyl amino side chains onto a pyrazole ring which had been incorporated into the anthraquinone chromophore. Compared with emodin, the derivatives had significantly higher DNA binding affinity based on interaction with calf thymus DNA, and much more potent cytotoxicity against different tumor cells. The derivatives with a mono-cationic alkyl side chain exhibited the highest DNA binding affinity and cytotoxicity. Publication Types: Research Support, Non-U.S. Gov't

Authored by Tan JH, Zhang QX, Huang ZS, Chen Y, Wang XD, Gu LQ, Wu JY. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, China.

Published in Eur J Med Chem. 2006 Sep;41(9):1041-7. Epub 2006 May 22. The full report is available online. A subscription to the periodical may be required.




David

This is amazing. So the 50/50 pills would actually be great for fighting cancer with the extra emodin if it weren't for the laxative effect. I wonder if that could be counteracted with the drink (2 tsp sugar, 1/4 tsp salt/ in 8 oz water) that Maxwatt recommended.

[davidd]

Emodin a good thing?

...

CONCLUSIONS: Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.

I included the above URL as part of a very long post in another topic (http://www.imminst.o...&...st&p=258905), but figured this particular point may be valuable to post here. I apologize if it has been covered before.

...

David

This is amazing. So the 50/50 pills would actually be great for fighting cancer with the extra emodin if it weren't for the laxative effect. I wonder if that could be counteracted with the drink (2 tsp sugar, 1/4 tsp salt/ in 8 oz water) that Maxwatt recommended.

I don't know what dose of emodin would be beneficial or even *if* it would be beneficial in vivo, but it is possible that a reasonable amount could be ingested without the laxative effect. I'm taking 600mg of 50% pure resveratrol now and I don't have any issues. (that's 200mg in each pill, 100 mg of which is resveratrol, and I take 6 pills/day) Of course, I don't know how much emodin is in the other 50% of the chemicals that are in the 200 mg of knotweed extract in the particular brand I'm taking.

I'm taking Country Life. I take 300mg in the morning and 300mg in the evening (6 pills total x 100 mg = 600 mg). If these have 5% emodin, then I'm taking 30mg in the morning and 30 mg in the evening. (.05*200 = 10 and 10x3 = 30) If they have 10% emodin, then I'm taking 60 mg in the morning and 60 mg in the evening.

The First Immortal is taking 25 times as much resveratrol as I am taking. I believe he's taking 15 grams currently (15/.6 = 25). If his supply has 1% emodin (if anyone knows, please respond), then he's at 150 mg already?? (15g * .01 = .15 g) This, I believe, is in 3 equal doses, so 50 mg three times per day. Of course, if his supply has less than 1%, then this amount is lower.

I just thought that maybe it couldn't *hurt* to throw some 50% pure capsules in the regimen?? But now that I do the math, he might have quite a bit of emodin already.

Does anyone know how much emodin is in what he is taking?

David

[missminni]

Emodin a good thing?

...

CONCLUSIONS: Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.

I included the above URL as part of a very long post in another topic (http://www.imminst.o...&...st&p=258905), but figured this particular point may be valuable to post here. I apologize if it has been covered before.

...

David

This is amazing. So the 50/50 pills would actually be great for fighting cancer with the extra emodin if it weren't for the laxative effect. I wonder if that could be counteracted with the drink (2 tsp sugar, 1/4 tsp salt/ in 8 oz water) that Maxwatt recommended.

I don't know what dose of emodin would be beneficial or even *if* it would be beneficial in vivo, but it is possible that a reasonable amount could be ingested without the laxative effect. I'm taking 600mg of 50% pure resveratrol now and I don't have any issues. (that's 200mg in each pill, 100 mg of which is resveratrol, and I take 6 pills/day) Of course, I don't know how much emodin is in the other 50% of the chemicals that are in the 200 mg of knotweed extract in the particular brand I'm taking.

I'm taking Country Life. I take 300mg in the morning and 300mg in the evening (6 pills total x 100 mg = 600 mg). If these have 5% emodin, then I'm taking 30mg in the morning and 30 mg in the evening. (.05*200 = 10 and 10x3 = 30) If they have 10% emodin, then I'm taking 60 mg in the morning and 60 mg in the evening.

The First Immortal is taking 25 times as much resveratrol as I am taking. I believe he's taking 15 grams currently (15/.6 = 25). If his supply has 1% emodin (if anyone knows, please respond), then he's at 150 mg already?? (15g * .01 = .15 g) This, I believe, is in 3 equal doses, so 50 mg three times per day. Of course, if his supply has less than 1%, then this amount is lower.

I just thought that maybe it couldn't *hurt* to throw some 50% pure capsules in the regimen?? But now that I do the math, he might have quite a bit of emodin already.

Does anyone know how much emodin is in what he is taking?

David

Maxwatt knows.

[thefirstimmortal]

We understand death for the first time when he puts his hand upon someone we love.


I will be gone for a few days up to Waterville Maine attending my Mothers funeral. She died this past Saturday afternoon of Cancer, leukemia. Her Mother, my Grandmother died 2 years ago of stomach cancer at the age of 89. My Grandparents on my Dad’s side are both still alive and in there 90’s. Until recently I thought I was swimming in the deep end of the gene pool, but clearly I am not. Or at least I didn’t win the gene pool longevity lotto.

You all live long and Well.
Be back in a few days.
William O’Rights

[jCole]

We understand death for the first time when he puts his hand upon someone we love.


I will be gone for a few days up to Waterville Maine attending my Mothers funeral. She died this past Saturday afternoon of Cancer, leukemia. Her Mother, my Grandmother died 2 years ago of stomach cancer at the age of 89. My Grandparents on my Dad's side are both still alive and in there 90's. Until recently I thought I was swimming in the deep end of the gene pool, but clearly I am not. Or at least I didn't win the gene pool longevity lotto.

You all live long and Well.
Be back in a few days.
William O'Rights

*positive vibes your way*

You have my sincere condolences William.

[Anthony_Loera]

Does anyone know how much emodin is in what he is taking?

David

Most 98% and 99% resveratrol have traces of emodin, usually about 0.04% or lower.

William, I am sorry to here of your loss.
My condolences go out to you and your family.

A

[davidd]

Does anyone know how much emodin is in what he is taking?

David

Most 98% and 99% resveratrol have traces of emodin, usually about 0.04% or lower.

A

Just clarifying. Is that 4% or truly .04% (= .0004)?

Thanks,
David

[bacopa]

My condolences Will, my mother died of colon cancer recently last January so I know what you're going through you don't deserve this kind of pain.

Devon

[davidd]

Does anyone know how much emodin is in what he is taking?

David

Most 98% and 99% resveratrol have traces of emodin, usually about 0.04% or lower.

A

Just clarifying. Is that 4% or truly .04% (= .0004)?

Thanks,
David

Looking back at this, it obviously isn't 4%. I think I meant to ask if it was .4% or .04%.

Assuming it is truly .04%, then that works out to 6mg (.0004*15000mg = 6mg). So 2 mg three times per day.

It does then seem plausible to add some 50% pure resveratrol to the mix to get a bit more emodin if the anti-lung cancer effects of emodin are to be given a chance.

What do you think of this, The First Immortal?

I know you are gone for a few days and I'm truly sorry to hear of your loss. But I figured I'd post this as something for you to consider when you return.

The thing that really caught my eye was that the first study was on small cell lung cancer, which I believe is the type you have? My thoughts on the study were that even if emodin doesn't knock out the cancer, maybe it will make it more susceptible to chemotherapy.


David

[Lufega]

Check out this blog. The writer is an immunologist and deals specifically with possible natural cures for cancer. Good luck!

http://www.grouppekurosawa.com/

[davidd]

Score another one for polyphenols!

In this case, Quercetin. And I know there is debate about quercetin inhibiting SIRT1, but SIRT1 might not be the most important aspect when trying to fight cancer.

http://dmd.aspetjour...t/full/34/2/296

What interested me about this study:

1) It was done on human small cell lung cancer.
2) It was done on quercetin metabolites rather than quercetin itself, so although it was an in vitro study, it should theoretically be closer to what happens in the body after quercetin passes through the liver.
3) It shows a dose and time dependent death of cancer cells to quercetin metabolites. More = better, faster = megadosing may mean megaresults.
4) Not part of the article, but quercetin may help more of the resveratrol get to its intended targets, as discussed in other threads.


Too big to post everything, but here are some excerpts. NCI-H209 is type of human small cell lung cancer.

...

INHIBITION OF LUNG CANCER CELL GROWTH BY QUERCETIN GLUCURONIDES VIA G₂/M ARREST AND INDUCTION OF APOPTOSIS
Jen-Hung Yang, Te-Chun Hsia, Hsiu-Maan Kuo, Pei-Dawn Lee Chao, Chi-Chung Chou, Yau-Huei Wei, and Jing-Gung Chung
...
Lung cancer is the leading cause of cancer death in many developed countries, including Taiwan. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells. Quercetin glucuronides are the main circulating metabolites after dietary supplements with quercetin in humans. However, there is little information available as to how quercetin glucuronides affect human cancer cells. We investigated the effects of quercetin glucuronides in a human lung cancer cell line NCI-H209. We checked the cell viability, cell cycle checkpoint proteins, pro- and antiapoptotic proteins, caspase-3 activity, and gene expression by flow cytometry and Western blot. The viability of cells decreased in a dose- and time-dependent manner. Cell cycle analysis revealed a significant increase of the proportion of cells in G₂/M phase and subG₀/G₁ phase (corresponding to apoptotic cells [davidd: apoptotic is my new favorite word!]). Moreover, quercetin glucuronides increased the expressions of cyclin B, Cdc25c-ser-216-p, and Wee1 proteins, indicating the G₂/M arrest. We also demonstrated a concurrent decrease of the mitochondrial membrane potential, release of cytochrome c, up-regulation of Bax, down-regulation of Bcl-2, and activation of caspase-3, and subsequently, cleavage of poly(ADP-ribose) polymerase. In addition, quercetin glucuronide-induced apoptosis was totally blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated that quercetin glucuronides inhibited proliferation through G₂/M arrest of the cell cycle and induced apoptosis [YAY! ] via caspase-3 cascade in the human lung cancer cell line NCI-H209. Delineation of the biological effects of specific major quercetin metabolites on chemotherapeutic potential or chemoprevention of human cancers warrants further investigation.
^...
Effects of Quercetin Glucuronides on Cell Viability of Lung Cancer NCI-H209 Cells. For control group, the data indicated that <2% of NCI-H209 cells were stained by trypan blue or propidium iodide when they were incubated in medium containing 10% FBS only. In the presence of quercetin glucuronides (0.5, 1, 2.5, 5, and 10 µM), the dye density of cultured cells was increased by the increase of the time and concentration used, suggesting that quercetin glucuronides exerted a dose-dependent cytotoxic effect on NCI-H209 cells (Fig. 2, A and B). The IC₅₀ value of quercetin glucuronides was approximately 34.8 µM.
...


Now, if a person wanted to obtain a 34.8 micromolar concentration of quercetin metabolites, how much would they need to consume?

I found another study (http://www.bio.unipd...Orzechowski.pdf) that referenced yet another study (http://www.ncbi.nlm..../pubmed/9103273), and the former (because I can't access the content of the latter) states:

"but in human beings who consume approximately 50-80 mg of quercetin per day, the plasma level generally does not exceed 1 µM"

The latter study states:

"The plasma quercetin concentration in subjects with an intact colon, after ingestion of fried onions, apples and pure quercetin rutinoside, decreased slowly with elimination half-lives of about 25 h. Thus, repeated dietary intake of quercetin will lead to accumulation in plasma."

Ah, so it has a cummulative concentration effect when taken daily! Good! But is it cummulative because it is in food form rather than supplement form? In other words, would the supplement form have a shorter half life?

And, when they talk about plasma concentrations, do they mean quercetin or the quercetain metabolites? I'll assume metabolites, since I've read elsewhere that other studies have shown no quercetin in the blood after being taken orally.

Anyway, using the above (and using 80mg = 1 micromolar), my crude math comes out to 2,784mg of quercetin to achieve 34.8 micromolar concentrations. The good news is that quercetin is relatively cheap.

I was taking a mixture that had bromelain in it as well, which is thought to further increase the bioavailability of quercetin. And on the topic of synergistic effects, I'll throw on this last study, which indicates it might also be a good idea to take some ellagic acid with the quercetin to make it even more potent.

I know some might say that ellagic acid is a red herring for anti-cancer remedies. I'm not suggesting the ellagic acid will have an anti-cancer effect by itself, but rather that it may help the quercetin do its thing.

http://jn.nutrition....tract/135/3/609

...

Ellagic Acid Potentiates the Effect of Quercetin on p21^waf1/cip1, p53, and MAP-Kinases without Affecting Intracellular Generation of Reactive Oxygen Species In Vitro^1,2

Susanne U. Mertens-Talcott, Joshua A. Bomser^*, Carlos Romero, Stephen T. Talcott and Susan S. Percival³

Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611-0370; ^* Department of Food Science and Technology, Ohio State University, Columbus, OH 43210-1007; and College of Veterinary Medicine, Department of Pathobiology, University of Florida, Gainesville, FL 32611-0880





³To whom correspondence should be addressed. E-mail: percival@ufl.edu . Anticarcinogenic effects attributed to polyphenols in fruits may be based on synergistic, additive, or antagonistic interactions of many compounds. In a previous study, it was demonstrated that quercetin and ellagic acid interacted synergistically in the induction of apoptosis in the human leukemia cell line, MOLT-4. To investigate possible cellular mechanisms, this study evaluated whether synergistic effects might be detectable within proapoptotic or antiproliferative signal transduction pathways. We found that quercetin and combinations of quercetin and ellagic acid nonsynergistically increased p53 protein levels. In contrast, ellagic acid potentiated the effects of quercetin for p21^cip1/waf1 protein levels and p53 phosphorylation at serine 15, possibly explaining the synergistic effect observed in apoptosis induction. Phosphorylation of the mitogen-activated protein (MAP) kinases, c-jun N-terminal (JNK)1,2 and p38, was also increased by the combination of ellagic acid and quercetin, whereas quercetin alone induced only p38. We further evaluated whether the generation of reactive oxygen species (ROS) and/or quercetin stability were influenced by interactions of ellagic acid with quercetin. Quercetin increased the generation of ROS, which was neither potentiated nor inhibited by ellagic acid. The stability of intracellular and extracellular quercetin was not influenced by the presence of ellagic acid. In summary, quercetin and ellagic acid combined increase the activation of p53 and p21^cip1/waf1 and the MAP kinases, JNK1,2 and p38, in a more than additive manner, suggesting a mechanism by which quercetin and ellagic acid synergistically induce apoptosis in cancer cells.
^...

The more I read about polyphenols, the more I think mother nature had it right and that we should be taking them together for maximum effect. In fact, I decided to google quercetin and ellagic acid and resveratrol to see if any studies have been done on the combination and here's what I found:

[url="http://"http://tinyurl.com/28w747""]http://tinyurl.com/2...yurl.com/28w747
<...san S. Percival^,

[/b]Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, P.O. Box 110370, Gainesville, FL 32611-0370, USA
Received 4 March 2004; revised 30 May 2004; accepted 3 June 2004. Available online 29 July 2004.

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<H3 class=h3>Abstract</H3>Anticarcinogenic effects of polyphenolic compounds in fruits and vegetables are well established. Although polyphenols naturally occur as combinations, little information is available regarding possible synergistic or antagonistic biochemical interactions between compounds. Identifying potential interactions between polyphenols may provide information regarding the efficiency of polyphenol-containing foods in cancer prevention. The objective of this study was to investigate the interactions of ellagic acid and quercetin with resveratrol, polyphenols which occur in muscadine grapes, with the hypothesis that the selected polyphenols would interact synergistically in the induction of apoptosis and reduction of cell growth in human leukemia cells (MOLT-4). To test this hypothesis, alterations in cell cycle kinetics, proliferation, and apoptosis (caspase-3 activity) were examined after incubation with ellagic acid, quercetin, and resveratrol as single compounds and in combination. Results showed a more than additive interaction for the combination of ellagic acid with resveratrol and furthermore, significant alterations in cell cycle kinetics induced by single compounds and combinations were observed. An isobolographic analysis was performed to assess the apparent synergistic interaction for the combinations of ellagic acid with resveratrol and quercetin with resveratrol in the induction of caspase 3 activity, confirming a synergistic interaction with a combination index of 0.64 for the combination of ellagic acid and resveratrol and 0.68 for quercetin and resveratrol. Results indicate that the anticarcinogenic potential of foods containing polyphenols may not be based on the effects of individual compounds, but may involve a synergistic enhancement of the anticancer effects.
...

Comments?

David

[stephen_b]

Hi TFE. I know that missminni has written a bit about vitamin E. Have you seen some research on tocotrienols? (From "Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs", PMID 18512238. Also see PMID 17628180. The more I read about the tocotrienol fraction of vitamin E, the more reasons I find to like it, and the more careful I am to have a better than 3:1 ratio of gamma tocopherol to alpha.

Current observations in the literature suggest that vitamin E may be a suitable candidate for the adjuvant treatment of cancer. Even though historically most research focused on alpha-tocopherol, more recent evidence suggests that the other isomers of vitamin E (beta-, gamma- and delta-tocopherols and alpha-, beta-, gamma- and delta-tocotrienols) differ in their proapoptotic potencies. [...] (i) no direct link exists between the antioxidant activity of each isomer/derivative and proapoptotic potency, (ii) tocotrienols are more effective proapoptotic agents than tocopherols, (iii) synthetic modifications of the naturally occurring compounds may improve their apoptotic potency and (iv) vitamin E isomers and derivatives regulate caspase-independent pathways of apoptosis. The latter combined with the evidence presented in this review regarding the additive or synergistic anticarcinogenic effects obtained when vitamin E analogs are used in combination with other cancer chemotherapeutic agents, supports further research to design the most promising vitamin E derivatives and clinically test them in adjuvant chemotherapeutic treatments.

Since cancer runs in my family, I added Jarrow TocoSorb to my list of anti-cancer supps. Curcumin is high on my list too; I fell prey to the LEF advertising juggernaut and spring for their bio-curcumin.

Stephen

[thefirstimmortal]

*positive vibes your way*

You have my sincere condolences William.

Thank you jCole.

[thefirstimmortal]

My condolences Will, my mother died of colon cancer recently last January so I know what you're going through you don't deserve this kind of pain.

Devon

Thank You Devon.

I too am sorry to hear about your loss.

My Mom passed by all accounts in a peaceful manner, mostly due to the morphine she was on. Her death was expected, and of course I feel the loss, but there was an extra sense of a different kind of feeling. They had to arrange the funeral at 11 am this morning so that I could leave to attend my chemo treatment. They mentioned my Grandmother, who passed with stomach cancer, and there I was, smack dab in the middle of the red zone of my own death prognosis attending my Mothers funeral who passed away from cancer. There were my direct ascendants both passed away from cancer.

I don’t want to sound macabre but now every time I look in the bathroom mirror, I see Death, the Eternal Footman (looking quite proud), standing in the shadows behind me, holding my coat, snickering.

[thefirstimmortal]

William, I am sorry to here of your loss.
My condolences go out to you and your family.

A

Thank You Anthony.