This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi
My wife was diagnosed with MS in 1996 (though she probably had first symptoms in 1993) and at that time was told it was RRMS. We live in Asia so she did Chinese medicine for 8 years till 2004 during which time she felt quite good. In 2005 she had her first episode of breast cancer. Had lumpectomy and radiation (interestingly the rads did not affect her from an MS standpoint). In 2009 she had another primary episode of breast cancer on the other breast and finally decided to have a double mastectomy. Since 2009 she has been on Tamoxifen.
Over the last few years - maybe a couple or maybe more - her MS symptoms seemed to have worsened in that where she could walk for 20-30 minutes previously now it may be 10 minutes. In the heat she is definitely worse than she used to be (she was bad earlier too but worse now) and in the cold while she did not have much of an issue, she does now. In the last three months started feeling a weakness in her right thigh that made her feel like she was dragging her foot/leg - this is the only new symptom in the last many years - all other symptoms are just a little worse or have gone away. Have met many MS specialists over the last three months and they say it MAY be SPMS now. Given her breast cancer - even though it was easy stage - many MS meds like Tysabri, Novantrone etc. are ruled out. She has been suggested to try Rituxan so this site has been very helpful in helping me understand what people on it have felt.

I will search to see if there are others with breast cancer on this site but there is a similar site for breast cancer called breastcancer.org where there are many ladies with both MS and BC and usually the MS was diagnosed first with BC some years later.

It is great to have resources like these sites available since one hears directly from the people who have the condition. Helps to also learn peoples experience with various treatments - e.g. the discussion on CCSVI where people have put down how they have felt before and after the procedure.

Here's wishing everyone good health and hoping a cure is out there somewhere in the not too distant future!

Hi
I was told I had MS in 2001 I know now I've had it for many years before that. My MS has progressed that I now use a walker around the house and either a wheelchair or a scooter . In 2009 I was diagnosed with breast cancer. Am doing quite well now. How's your wife doing. Was wondering if you found any link between the two? Good luck

Recently, there was an item on the CBS evening news about sugar being toxic, cancer growths having insulin receptors on the surface, and the connection of glucose with about 10 different types of cancer.

Here is a link to the 14 minute video segment, straight from American TV: (http://www.cbsnews.com/video/watch/?id= ... contentAux).

There have been many articles pointing out a connection between the diabetes drug metformin (Glucophage) and improvements in several cancers:
http://www.reuters.com/article/2009/09/ ... SF20090914

This sentence in the following article: "the new finding is in line with previous research suggesting that metformin may decrease the risk of multiple cancers, said Dr. Peter Butler, a diabetes researcher at the University of California, Los Angeles David Geffen School of Medicine, who wasn't involved in the new study," amazed me: http://www.reuters.com/article/2012/01/ ... ZQ20120131

I suspect that insulin with its growth factor is promoting cancer growth; and when metformin reduces the glucose, the insulin level goes down too. I think this accounts for the improvement in these different cancers.

_________________
My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"

interesting studies:

Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments
http://www.ncbi.nlm.nih.gov/pubmed/15754125


i wonder what the effects of copaxone might be, compared to beta-interferons.

Cancer risk and impact of disease-modifying treatments in patients with multiple sclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/18420778


might i ask what chinese medicines in particular were used to treat your wife's ms from 1996 to 2004? i don't know anything about traditional chinese med but found this list - Rei Shi, Lu Feng Fang, Long Kui, Ban Zhi Lian, Dong Ling Cao, and Bai Hua She She. Could be interesting to discover whether some of these treatments contain compounds with comparable effects on the body as treatments like glatiramer acetate (copaxone).

at any rate, here is an interesting study linking nutrition and cancer incidence:

Zinc deficiency, DNA damage and cancer risk
http://www.ncbi.nlm.nih.gov/pubmed/15542347
article full text
http://www.aseanfood.info/articles/11013850.pdf

you may also be interested in reading about altered copper-zinc ratios in breast cancer and multiple sclerosis:

Serum copper and zinc levels and copper/zinc ratio in patients with breast cancer
http://www.springerlink.com/content/y3p3321678738p73/
"The mean serum copper level and the mean Cu/Zn ratio in patients with breast cancer were significantly higher than the control group (p<0.001 andp<0.001). In addition, the mean serum zinc level in patients with breast cancer was significantly lower than the control group (p<0.001)."

Zinc and copper in multiple sclerosis
http://www.ncbi.nlm.nih.gov/pmc/article ... 2-0029.pdf

this second study link goes to full text - at first glance i'm not seeing ratios compared specifically, but you can see that although the abstract talks about both copper and zinc being lower in ms patients, that the ratio would change over time to strongly favour copper levels. check out the figures on page 693 where ms patient copper levels increase over time compared to decreasing levels in healthy controls.

_________________
my approach: no meds so far - just balanced whole foods (partial 'paleo', much less outright elimination), science, supplements, & bloodwork
my regimen - www.thisisms.com/ftopict-2489.html
www.whfoods.com, www.nutritiondata.com

Anecdotally, I have heard of many people with cancer who go on to be diagnosed with MS. This week I was watching Your World with Neil Cavuto, who has MS; he mentioned that he first was diagnosed with cancer. He mentioned that Ann Romney had had breast cancer and then was diagnosed with MS. Although I have MS, I have had no previous cancer.

This week I also found the following article, not recently published:

"Diabetes drug tied to less cancer, has docs excited
... The new reports, one from China and one from Italy, still don't offer proof that metformin cuts people's cancer risks. But they bolster the case that it might. ..."
Thu Nov 11, 2010

http://www.reuters.com/article/2010/11/ ... PX20101111

_________________
My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"

also of potential interest regarding the copper-zinc ratio:

Copper/zinc ratio and systemic oxidant load: effect of aging and aging-related degenerative diseases
http://www.sciencedirect.com/science/ar ... 4998001099


also, yay for full text!
Copper, Zinc, Manganese, and Magnesium Status and Complications of Diabetes Mellitus
http://care.diabetesjournals.org/conten ... 0.full.pdf


now that last study abstract contains a whole lot of 'makes no sense' to my brain, but luckily having the full text we can (hopefully) figure out what they meant by being both 'hyper' and 'lower' for zinc, while being both 'hyper' and 'no difference' for magnesium...

oh dear. both groups are really bad for average serum zinc levels, with controls at 11.7 ± 0.6 umol/L vs diabetics at 9.9 ± 0 umol/L!!! so the diabetics are outright deficient if using the 'normal' range, while even some of the controls are deficient, with probably just over half of them barely squeezing into the bottom end of 'normal' (defined in research as 11.5-18.5 umol/L). the control subjects are described as 'free of apparent illness' - hmm, give it time, give it time...

as for copper, controls averaged 13.2 ± 0.6 umol/L and diabetics averaged 16.6 ± 0.8 umol/L. so as for the zinc-copper ratio, controls are a lot closer to 1 to 1 (0.96 ± 0.06) while diabetics are closer to 1 to 2! (0.65 ± 0.03).

also, as far as magnesium goes, both groups are very close to the bottom end of the 'normal' range (usually defined as 0.70 - 1.10 mmol/L). controls averaged 0.77 ± 0.02 mmol/L while diabetics averaged 0.73 ± 0.02 mmol/L. again, give it time, controls...

conclusion: (thank you, full text!)

am i crazy, or did the SEVEN research professionals who put their names on this paper mean to type 'hypo' not 'hyper' in the abstract, for both zinc and magnesium? yay for the peer-review process :S

and now with that correction, in certain ways the rest of the abstract makes sense, for example their finding no significant differences between groups for magnesium, because both groups had quite poor status. i think i would have been clear in the abstract that both groups had low normal magnesium status and that the diabetics did have lower serum magnesium on average, but without achieving 'statistical significance'. other researchers have found that serum/plasma magnesium should be at least 0.90 mmol/L.

very interesting!

link to older discussion on zinc, magnesium and insulin
natural-approach-f27/topic18579-15.html#p64721

_________________
my approach: no meds so far - just balanced whole foods (partial 'paleo', much less outright elimination), science, supplements, & bloodwork
my regimen - www.thisisms.com/ftopict-2489.html
www.whfoods.com, www.nutritiondata.com

Maybe if you suppress the immune system with these drugs the immune system cannot fight diseases like cancer. That could be another side effect of these drugs. Best to use diet.

I have a real probability of having prostate cancer so I have altered my supplment intake to one that is highly anti-cancer.

My latest supplment is..... Pterostilbene

http://en.wikipedia.org/wiki/Pterostilbene

http://www.ihealthdirectory.com/pterostilbene/

I take 50 mg twice a day.

http://www.vitaminshoppe.com/store/en/b ... ku=JF-7342







The latest study indicates that it is effective against Breast Cancer.



It seems harmless and has other health benefits. I take it with 200 mg of Resveratrol and 500 mg of Quercetin daily. I may increase my Pterostilbene to three 50 mg capsules a day.

jackD

p.s. This is a VERY HOT subject of research and some internet sites may not be current.

check http://www.pubmed.gov for the latest. Search on "Pterostilbene cancer".

hey there jack, what is your whole daily regimen, iima?

_________________
my approach: no meds so far - just balanced whole foods (partial 'paleo', much less outright elimination), science, supplements, & bloodwork
my regimen - www.thisisms.com/ftopict-2489.html
www.whfoods.com, www.nutritiondata.com

i wrote the bones of this post almost a year ago, for someone else - but with a couple slight modifications it could be useful here...

Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer
http://cancerres.aacrjournals.org/conte ... 5882.short
"biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-?-trypsin inhibitor heavy chain H4 (up-regulated)."

...zinc regulates apolipoprotein A1 expression

Transcriptional Control of Apolipoprotein A-I Gene Expression in Diabetes
http://diabetes.diabetesjournals.org/co ... 3/513.full
"...some micronutrients have been found to have an important modulatory role in apo A-I gene expression (60,61). In particular, zinc deficiency causes downregulation of apo A-I expression (59), whereas supraphysiologic concentrations of zinc, as well as chromium or vanadium, downregulate apo A-I promoter activity (61). Some of the effects of zinc deficiency may be explained by the dependence of zinc finger-containing transcription factors, such as Sp1, for the coordinating effect of zinc ions."

INSERT i had found this later and forwarded, just squeezing it in here...

Changes of serum-zinc in breast cancer (author's transl)].
"Serum-zinc-levels were evaluated in patients with breast cancer in relation to the various stages. Patients with metastatic breast cancer had significantly depressed zinc-levels, wereas patients with disease apparently localized to the breast and draining lymphnodes had nearly normal serum zinc levels. It appears that the determination of serum zinc in breast cancer patients may be of value in discriminating between localized and metastatic disease." END OF INSERT

so if apo A-I is downregulated in cancer and zinc deficiency causes apo A-I downregulation.. might be a plan to check that zinc status!

selenium down-regulate(s) transthyretin (in an animal study) (selenium status is also down in MS patients)

Selenium deficiency decreases expression of the genes for transthyretin
http://www.sciencedirect.com/science/ar ... 1796002643

"...mRNA levels for transthyretin and citrate transport protein are both reduced in the livers of Se-deficient rats. Reductions averaged 44.7% (p=0.0009) for transthyretin and 42.8% (p=0.0032) for citrate transport protein. These results suggest a coordinated regulation of thyroid hormone metabolism in rats by dietary Se intake."

I can't find anything comprehensible for item c), inter-?-trypsin etc.

on to vitamin D... (also a risk factor for ms)

Vitamin D and prevention of breast cancer: Pooled analysis
http://www.sciencedirect.com/science/ar ... 6006003918
Intake of 2000 IU/day of Vitamin D3, and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

Serum Levels of Micronutrients, Antioxidants and Total Antioxidant Status Predict Risk of Breast Cancer in a Case Control Study
http://jn.nutrition.org/content/132/2/303.short
"We conclude that increased serum levels of ß-carotene, retinol, bilirubin and total antioxidant status are associated with reductions in breast cancer risk."

Prospective Study of Carotenoids, Tocopherols, and Retinoid Concentrations and the Risk of Breast Cancer
http://cebp.aacrjournals.org/content/11/5/451.short
"Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort ... and for lutein in the 1989 cohort ... The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene, lycopene, and total carotene in the 1974 cohort."

Plasma Carotenoids, Retinol, and Tocopherols and Risk of Breast Cancer
http://aje.oxfordjournals.org/content/161/2/153.short
"The multivariate risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of beta-carotene..., beta-carotene..., lutein/zeaxanthin..., and total carotenoids... The inverse association observed with beta-carotene and breast cancer was greater for invasive cancers with nodal metastasis."

Serum Retinol, Beta-Carotene, Vitamin E, and Selenium As Related to Subsequent Cancer of Specific Sites
http://aje.oxfordjournals.org/content/135/2/115.short
"For all four nutrients, the majority of results showed lower levels among persons who subsequently became cases than among controls. Low levels of beta-carotene were most likely to be associated with subsequent cancer, but there were marked differences by cancer site."

RRR-alpha-tocopherol induces human breast cancer cells to undergo apoptosis via death receptor 5 (DR5)-mediated apoptotic signaling
http://www.cancerletters.info/article/S0304-3835(07)00479-X/abstract
"Thus, [gamma-tocopherol] is a potent pro-apoptotic agent for human breast cancer cells inducing apoptosis via activation of DR5-mediated apoptotic pathway."

My comment: this study used synthetic gamma tocopherol to successfully kill off cancer cells. In past studies, the use of synthetic alpha tocopherol, intended to test protection against prostate cancer, actually drove down gamma tocopherol levels in subjects, and cancer risk increased. Of course natural food source gamma tocopherol is much better that synthetic sources. Fortunately, there is no known toxicity resulting from consuming vitamin E rich foods.

hope you find this useful, nim.

_________________
my approach: no meds so far - just balanced whole foods (partial 'paleo', much less outright elimination), science, supplements, & bloodwork
my regimen - www.thisisms.com/ftopict-2489.html
www.whfoods.com, www.nutritiondata.com

This is a really BIG subject area. I am going to piss on a lot of folks "Pet" ideas. I expect to get a lot of those my uncle/aunt took that for ten years and he/she is not dead yet!!

So here it is.

jackD

p.s. I am NOT going to just list them. I am going to present them one at a time with a representative abstract from NIH-NLM to indicate it is effective or promising.

I like Tocotrienols a lot. They are God's gift to neurons AND they are highly anti-cancer.

Carcinogenesis. 2012 Feb;33(2):233-9. Epub 2011 Nov 17.

Tocotrienol as a potential anticancer agent.
Ling MT, Luk SU, Al-Ejeh F, Khanna KK.
SourceAustralian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Qld 4102, Australia. mingtat.ling@qut.edu.au

Abstract
Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers.

A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity.

More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment. This review will summarize recent developments in the understanding of the anticancer effects of T3. We will also discuss current progress in clinical trials involving T3 as an adjuvant to conventional cancer therapy.

PMID:22095072[PubMed - in process]

I like this form of Vitamin E also. It comes in my Multivitamin.

jackD



Int J Cancer. 2006 May 15;118(10):2441-7.

Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis.

Malafa MP, Fokum FD, Andoh J, Neitzel LT, Bandyopadhyay S, Zhan R, Iiizumi M, Furuta E, Horvath E, Watabe K.

SourceDivision of GI Tumors, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Abstract
Prostate cancer is a major cause of cancer death and morbidity in western countries. However, because of its intrinsic nature of chemoresistance, there is only limited systemic therapy available for the patients. Vitamin E (VE) has been under intensive study as a chemopreventive agent for various types of cancers. Preclinical studies suggest that vitamin E succinate (VES) is the most effective antitumor analogue of VE, yet there are scarce studies of VES in prostate cancer.

In this study, we investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer.

Our results indicate that VES significantly inhibited proliferation and induced apoptosis of prostate cancer cell lines in a dose and time dependent manner.

The results of microarray analysis followed by real-time RT-PCR and inhibitor analyses indicated that the VES-induced apoptosis is mediated by caspase-4 in prostate tumor cells.

In our animal model of prostate cancer in SCID mouse, daily injection of VES significantly suppressed tumor growth as well as lung metastases.

These results suggest a potential therapeutic utility of VES for patients with prostate cancer.

Copyright (c) 2005 Wiley-Liss, Inc.

PMID:16380976[PubMed - indexed for MEDLINE]

I also like Astaxanthin.

jackD


Molecules. 2012 Mar 14;17(3):3202-42.

Cancer chemoprevention by carotenoids.

Tanaka T, Shnimizu M, Moriwaki H.
SourceTohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-Uzura, Gifu 500-8285, Japan. takutt@toukaisaibou.co.jp.

Abstract
Carotenoids are natural fat-soluble pigments that provide bright coloration to plants and animals. Dietary intake of carotenoids is inversely associated with the risk of a variety of cancers in different tissues. Preclinical studies have shown that some carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles for the compounds. Since chemoprevention is one of the most important strategies in the control of cancer development, molecular mechanism-based cancer chemoprevention using carotenoids seems to be an attractive approach. Various carotenoids, such as β-carotene, a-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti-carcinogenic activity in several tissues, although high doses of β-carotene failed to exhibit chemopreventive activity in clinical trials. In this review, cancer prevention using carotenoids are reviewed and the possible mechanisms of action are described.

PMID:22418926[PubMed - in process]



J Herb Pharmacother. 2005;5(1):17-26.

A preliminary investigation of the enzymatic inhibition of 5alpha-reduction and growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and Saw Palmetto lipid extract in vitro.

Anderson ML.
SourceResearch and Development, Triarco Industries, Wayne, NJ 07470, USA. mark.anderson@triarco.com

Abstract
Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alpha-reductase and decrease the clinical symptoms of BPH. Epidemiologic studies report that carotenoids such as lycopene may inhibit prostate cancer.

In this investigation the effect of the carotenoid astaxanthin, and SPLE were examined for their effect on 5alpha-reductase inhibition as well as the growth of prostatic carcinoma cells in vitro. These studies support patent #6,277,417 B1.

The results show astaxanthin demonstrated 98% inhibition of 5alpha-reductase at 300 microg/mL in vitro.

Alphastat, the combination of astaxanthin and SPLE, showed a 20% greater inhibition of 5alpha-reductase than SPLE alone n vitro. A nine day treatment of prostatic carcinoma cells with astaxanthin in vitro produced a 24% decrease in growth at 0.1 mcg/mL and a 38% decrease at 0.01 mcg/mL. SPLE showed a 34% decrease at 0.1 mcg/mL.

CONCLUSIONS: Low levels of carotenoid astaxanthin inhibit 5alpha-reductase and decrease the growth of human prostatic cancer cells in vitro. Astaxanthin added to SPLE shows greater inhibition of 5alpha-reductase than SPLE alone in vitro.

PMID:16093232[PubMed - indexed for MEDLINE]

Biochem Biophys Res Commun. 2012 Apr 1. [Epub ahead of print]

Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate.

Min NY, Kim JH, Choi JH, Liang W, Ko YJ, Rhee S, Bang H, Ham SW, Park AJ, Lee KH.
SourceDepartment of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Republic of Korea.

Abstract
(-)-Epigallocatechin-3-gallate (EGCG) induces apoptosis in cancer cells without adversely affecting normal cells. Understanding the cancer-specific cytotoxic activity of EGCG is very important in defining the mechanism of tumorigenesis and identifying superb chemotherapeutic agents against cancer. We comparatively assayed human telomerase reverse transcriptase (hTERT)-mediated apoptosis by EGCG-induced reactive oxygen species (ROS) in normal cells and cancer cells. EGCG showed differential levels of ROS induction between the cell types; ROS, especially hydrogen peroxide, was highly induced in cancer cells, while it was not in normal cells. In addition, the higher level of ROS down-regulated hTERT via binding of CCCTC binding factor (CTCF) to the core promoter region of hTERT, which repressed hTERT expression. CTCF binding was epigenetically controlled by the demethylation of the previously hypermethylated site for CTCF, which was induced by down-regulation of DNA methyltransferase 1 (DNMT1). In contrast, hTERT down-regulation was not observed in normal cells. These results suggest that preferential death of cancer cells by EGCG could be caused by the cancer-specific induction of ROS and epigenetic modulation of expression of apoptosis-related genes, such as hTERT.

Copyright © 2012. Published by Elsevier Inc.

PMID:22487794[PubMed - as supplied by publisher]

Int J Oncol. 2004 Mar;24(3):703-10.

EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis.

Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar SK.
SourceDepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract
Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied ( approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%).

In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT.

Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer.

PMID:14767556[PubMed - indexed for MEDLINE]



Phytomedicine. 2010 Apr;17(5):356-62. Epub 2010 Feb 10.

(-)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line.

Farabegoli F, Papi A, Bartolini G, Ostan R, Orlandi M.
SourceDepartment of Experimental Pathology, Via San Giacomo, 14, University of Bologna, 40126 Bologna, Italy. fulvia.farabegoli@unibo.it

Abstract
We investigated the anticancer effect of EGCG treatment on a breast carcinoma cell line resistant to tamoxifen (MCF-7Tam cells). As there are no reports about the molecular mechanisms implicated in EGCG treatment of tamoxifen resistant breast carcinoma cells, we studied the effects of EGCG treatment on three plasma membrane proteins that are involved in the mechanism of drug-resistance: Multidrug Resistance Protein (MRP1), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). EGCG treatment (10-100 microg/ml for 24-72 hours) caused cell growth inhibition and dose-dependent apoptosis: after 100 microg/ml EGCG treatment for 24 hours, Bax expression increased and Bcl2 expression decreased (p<0.05). Coherently, Annexin V-FITC apoptosis assay detected a significant increase in labelled cells (p<0.05). EGCG did not affect MRP1: in contrast, 100 microg/ml EGCG administration caused P-gp decrease to 53% of control cells (p<0.001) and this effect was not due to downregulation of P-gp gene expression. EGCG induced P-gp decrease even when MG132, a strong proteasome inhibitor, was given together with EGCG to MCF-7Tam cells. EGCG treatment also inhibited BCRP activity: mRNA transcription and protein level did not change after treatment, but mitoxantrone test demonstrated a strong inhibition of BCRP activity (p<0.001). In conclusion, the present results showed that EGCG could down-regulate the activity of two molecules that play a key role in drug metabolism and transport and that are highly expressed in tamoxifen resistant breast carcinoma cells. The interaction of EGCG and drugs used in the therapy of estrogen sensitive breast carcinoma ought to be subject of studies and the potential use of EGCG in drug-resistant diseases ought to be better considered.

Copyright 2010 Elsevier GmbH. All rights reserved.

PMID:20149610[PubMed - indexed for MEDLINE]

I drink Pomegranate juice and take Pomegranate extract and eat fresh Pomegranates. I found that I can keep them in my refrigerator for 12 months. They do take up a lot of space.

jackD

Nutr Cancer. 2009;61(6):811-5.

Cancer chemoprevention by pomegranate: laboratory and clinical evidence.

Adhami VM, Khan N, Mukhtar H.

Department of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Pomegranate fruit from the tree Punica granatum has been dubbed as the "nature's power fruit." Dating back to Biblical times, the tree itself is attributed to possess extraordinary medicinal properties. The geographical distribution of the tree, being native to the Middle East and some Asian countries, is generally attributed to a lack of interest in its medicinal properties by many western scientists. However, the unique biochemical composition of the pomegranate fruit being rich in antioxidant tannins and flavonoids has recently drawn attention of many investigators to study its exceptional healing qualities.

Recent research has shown that pomegranate extracts selectively inhibit the growth of breast, prostate, colon and lung cancer cells in culture.

In preclinical animal studies, oral consumption of pomegranate extract inhibited growth of lung, skin, colon and prostate tumors. An initial phase II clinical trial of pomegranate juice in patients with prostate cancer reported significant prolongation of prostate specific antigen doubling time. This review focuses on recent investigations into the effects of pomegranate fruit on cancer.


PMID: 20155621 [PubMed - indexed for MEDLINE] PMCID: PMC298979



Carcinogenesis. 2012 Mar;33(3):644-51. Epub 2011 Dec 22.

Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model.

Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H.

Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA.

We earlier provided evidence that oral consumption of pomegranate fruit extract (PFE) inhibits prostate cancer (PCa) cell growth in nude mice. To ascertain convincing evidence of chemopreventive effects of PFE against PCa, its efficacy requires to be evaluated in animal models that closely emulate human disease.

Here, we provide evidence of remarkable tumor growth inhibitory effects of PFE using the TRAMP model. Mice received 0.1 and 0.2% PFE, equivalent to 250 and 500 ml of pomegranate juice, in drinking water, starting at 6 weeks and examined at 12, 20 and 34 weeks of age. In water-fed group, 100% mice developed palpable tumors by 20 weeks compared with only 30 and 20% in the 0.1 and 0.2% PFE-supplemented groups, respectively. At 34 weeks, palpable tumors were observed in 70 of 0.1% and only 50 of 0.2% PFE-supplemented mice. Compared with median survival of 43 weeks in water-fed mice, 0.1 and 0.2% PFE-supplemented mice exhibited median life expectancy of 73 and 92 weeks, respectively. Compared with respective water-fed groups, none of the mice in PFE-supplemented groups exhibited metastases to any of the distant organs at 20 weeks and only 20% mice exhibited metastasis at 34 weeks of age. Many of the PFE-supplemented animals had multiple foci of well-differentiated carcinoma but no evidence of poorly differentiated carcinoma.

PFE supplementation resulted in simultaneous and significant inhibition of IGF-I/Akt/mTOR pathways in the prostate tissues and tumors. We suggest that pomegranate juice be evaluated in clinical trials in patients at high risk for developing PCa.


PMID: 22198212 [PubMed - in process] PMCID: PMC3291862