11 replies to this topic

[Soma]

In the Book Important Facts About Cancer Prevention, Dr. Abdelfattah Mohsen Badawi writes, "Despite promising results in preclinical settings, the applicability of these agents [curcumin, epigallocatechin, resveratrol, and thymoquinone] to humans has met with little success, largely due to inefficient systemic delivery and bioavailability. For example, the study of the pharmacokinetics of resveratrol in humans concluded that even high doses of reseveratrol might be insufficient to achieve resveratrol concentrations required for the systemic prevention of cancer. Similarly, the amount of curcumin and EGCG required to observe anticancer effects in humans is too high to be feasibly incorporated into a clinical trial due to acute toxicity."

I know that there are many of this site that consume these compounds for their purported anticancer properties. It seems that humans would have to consume toxic quantities of these compounds to have any appreciable effect on cancer. We may have better delivery methods and/or bioavailability enhancers in the furue, but as it stands right now, these supplements (if used for chemoprotection) are essentially useless.

[joelcairo]

IMO Badawi is talking rubbish. There is a vast literature showing that many supplements have beneficial effects and anticancer activity at clinically relevant dosages. IMO the main barrier to general adoption of such agents is a persistent and scandalous lack of clinical trials.

 

[Kalliste]

Problem is the studies he refers too are poorly designed. They test each compound in isolation and conclude it does nothing.

 

What is needed is multifactorial trials that target multiple cancer pathways, eg. Fasting, HIT, carefully selected supplement combinations, chemo and radiation. All in one. Those kind of trials are non existent.

 

 

Free Radic Biol Med. 2006 Jan 15;40(2):341-7.

The induction of human superoxide dismutase and catalase in vivo: a fundamentally new approach to antioxidant therapy.

Nelson SK¹, Bose SK, Grunwald GK, Myhill P, McCord JM.

Author information

• ¹Webb-Waring Institute for Cancer, Aging and Antioxidant Research, University of Colorado Denver Health Sciences Center, Denver, CO 80262, USA.

Abstract

A composition consisting of extracts of five widely studied medicinal plants (Protandim) was administered to healthy human subjects ranging in age from 20 to 78 years. Individual ingredients were selected on the basis of published findings of induction of superoxide dismutase (SOD) and/or catalase in rodents in vivo, combined with evidence of decreasing lipid peroxidation. Each ingredient was present at a dosage sufficiently low to avoid any accompanying unwanted pharmacological effects. Blood was analyzed before supplementation and after 30 and 120 days of supplementation (675 mg/day). Erythrocytes were assayed for SOD and catalase, and plasma was assayed for lipid peroxidation products as thiobarbituric acid-reacting substances (TBARS), as well as uric acid, C-reactive protein, and cholesterol (total, LDL, and HDL). Before supplementation, TBARS showed a strong age-dependent increase. After 30 days of supplementation, TBARS declined by an average of 40% (p = 0.0001) and the age-dependent increase was eliminated. By 120 days, erythrocyte SOD increased by 30% (p < 0.01) and catalase by 54% (p < 0.002). We conclude that modest induction of the catalytic antioxidants SOD and catalase may be a much more effective approach than supplementation with antioxidants (such as vitamins C and E) that can, at best, stoichiometrically scavenge a very small fraction of total oxidant production.

 

 

PLoS One. 2010 Jul 30;5(7):e11902. doi: 10.1371/journal.pone.0011902.

The chemopreventive effects of Protandim: modulation of p53 mitochondrial translocation and apoptosis during skin carcinogenesis.

Robbins D¹, Gu X, Shi R, Liu J, Wang F, Ponville J, McCord JM, Zhao Y.

Author information

• ¹Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.

Abstract

Protandim, a well defined dietary combination of 5 well-established medicinal plants, is known to induce endogenous antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Our previous studies have shown through the induction of various antioxidant enzymes, products of oxidative damage can be decreased. In addition, we have shown that tumor multiplicity and incidence can be decreased through the dietary administration of Protandim in the two-stage skin carcinogenesis mouse model. It has been demonstrated that cell proliferation is accommodated by cell death during DMBA/TPA treatment in the two-stage skin carcinogenesis model. Therefore, we investigated the effects of the Protandim diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA induced cutaneous apoptosis. Recently, more attention has been focused on transcription-independent mechanisms of the tumor suppressor, p53, that mediate apoptosis. It is known that cytoplasmic p53 rapidly translocates to the mitochondria in response to pro-apoptotic stress. Our results showed that Protandim suppressed the mitochondrial translocation of p53 and mitochondrial outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD expression/activity in murine skin JB6 promotion sensitive (P+) and promotion-resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells, not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+ cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found that the introduction of wild-type p53 promoted transformation in JB6 P- cells. Our results suggest that suppression of p53 and induction of MnSOD may play an important role in the tumor suppressive activity of Protandim.

 

Cancer doctors know this is a problem and some want to do something about it, I suspect many don't care because it will not be profitable.

 

 

Targeting DNA repair, DNA metabolism and replication stress as anti-cancer strategies

Authors

• Jordi Carreras Puigvert,
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  1. Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

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  • These authors contributed equally to this work.

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• Kumar Sanjiv,
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  1. Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

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  • These authors contributed equally to this work.

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• Thomas Helleday
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  Corresponding author

  1. Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

  • Correspondence

    T. Helleday, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden

    Fax: +46 8 31 11 01

    Tel: +46 8 524 800 00

    E-mail: thomas.helleday@scilifelab.se

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• First published: 18 November 2015Full publication history
• DOI: 10.1111/febs.13574View/save citation
• Cited by: 0 articles Check for new citationsCiting literature
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• Funding Information

 

 

Abstract

Anti-cancer therapies targeting and damaging the DNA have been extensively used in the last 50 years since the discovery of nitrogen mustards, antimetabolites and platin agents. The use of these drugs is often limited by dose-limiting side effects related to their poor specificity. In recent years, much effort has been put on the discovery and development of compounds that would exploit defects in DNA repair in cancer cells such as Wee1, Chk1 or PARP1 inhibitors. However, not all cancers respond to these inhibitors. Recently, new developments towards specifically targeting broader characteristics of cancer such as replication stress (RS) and lost redox homeostasis have emerged. Oncogenes induce proliferation signals, which also result in replication-associated DNA damage, i.e. RS. Our knowledge into overall causes of RS, lesions produced and how these are signalled in cells to activate cell cycle checkpoints is evolving. Inhibition of ATR, which would normally keep non-deleterious levels of RS, induces intolerable RS levels for cancer cells. Interestingly, links between replication and transcription appear to underlie RS along with a reduction of the dNTP pool. Remarkably, sanitization of the dNTP pool by MutT homologue 1, impeding incorporation of oxidized dNTPs into the DNA, seems to be crucial for cancer cell survival. In this minireview we present an overview of current and novel strategies to target DNA repair and exploit DNA damage to treat cancer. We present the current models for cancer-associated RS as well as cancer phenotypic lethality. Both strategies are poised to better target cancer cells and reduce side effects.

 

Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

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DOI: 10.4236/pp.2015.63017    1 555 Downloads   1 958 Views   Citations

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Safaa Yehia Eid^1,2, Mahmoud Zaki El-Readi^1,2,3*, Sameer Hassan Fatani¹, Essam Eldin Mohamed Nour Eldin¹, Michael Wink^2*

 

 

ABSTRACT

Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclus

Affiliation(s)

¹Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia.
²Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
³Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.

ion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.

 

[Mind]

The problem is perception. Some of these compounds have shown "moderate" anti-cancer effects. The general public/media will generally hype the results and proclaim such substances are "cures".

 

Just stop and think about "natural" cancer "cures"- from Chinese herbs to resveratrol, to curcumin - if these actually reliably CURED cancer, people would have known about it hundreds of years ago and no one would die of cancer.

 

That being said, if I developed cancer I would try a multi-factorial approach, including some "natural" stuff, and fasting.

[Dorian Grey]

I've often wondered if someone actually did get a remarkable cancer/remission response from a supplement, who might actually believe them.  Doctors pounce on supplement cancer cure claims as quacks and frauds about as aggressively as they do anti-vax'ers, and doctors who dare to experiment with alternative therapies risk being run out of town on a rail.  

 

IP6 is my pet supplement, with a lot of anti-cancer hope and hype associated with it.  Whilst surfing around on IP6 I found a "lung cancer survivor's forum" with a couple of remarkable posts on IP6 I copied to my second post in this thread.  

 

http://www.longecity...ll-lung-cancer/

 

Here we see Elroy casually chatting about his lung cancer that had spread to his lymph nodes but vanished after only 3 rounds of chemo and IP6 he started on shortly after being diagnosed.  

 

Carol chimes in and says she's been on IP6 since her surgery "almost 5 years ago"!  

 

Anyone with knowledge about lung cancer cure and/or 5 year survival rates might be impressed with these admittedly small samples of anecdotal posts.  I know I was!  Who knows how many more there are like this?  I doubt their doctors wrote up the possible contribution of IP6 with their therapies in any medical journal.  

 

Anyway...  Here's a few more clues for you all.

 

IP6 appears to stimulate repair of double strand breaks in DNA http://www.ncbi.nlm....pubmed/11030616

 

Here's a full monty report: http://jn.nutrition....3/11/3778S.full

 

No "Proof" to be sure, but isn't medicine "Evidenced Based?"  IP6 is cheap and side effects next to nil...  If you were diagnosed with a particularly nasty cancer (lung, pancreas, melanoma), how long would you wait for more evidence or perhaps proof of effect?  

Edited by synesthesia, 09 February 2016 - 01:50 AM.

[message]

Does ip6 do anything for otherwise healthy people?

[Dorian Grey]

Does ip6 do anything for otherwise healthy people?

 

There's a pretty good list of benefits here: http://selfhacked.co...aging-compound/

 

(Phytic Acid another name for IP6)

 

• 3 1) Phytic Acid is an Anti-oxidant.
• 4 2) Phytic Acid Reduces Inflammation.
• 5 3) Phytic Acid Induces Autophagy
• 6 4) Phytic Acid Has Potential For Treating Multiple Cancers
• 7 5) Phytic Acid Benefits Blood Glucose Control
• 8 6) Phytic Acid is Neuroprotective
• 9 7) Phytic Acid Reduces Triglycerides and Increases HDL
• 10 8) Phytic Acid  Repairs DNA
• 11 9) Phytic Acid Increases Bone Mineral Density
• 12 10) Phytic acid protects human skin from UVB exposure
• 13 11) Phytic Acid Can Protect The Gut From Toxins
• 14 12) Phytic Acid Helps Prevent Kidney Stones
• 15 13) Phytic acid binds to Heavy Metals, Mycotoxins, Uranium, Iron, Manganese   
• 16 14) Phytic Acid Decreases Uric Acid/Helps Gout
• 17 15) Phytic Acid is Anti-HIV
• 18 16) Phytic Acid Increases The Bioavailability of Flavones

Just one cap/day taken on a very empty stomach with plain water is all you need for prophylaxis, and at a dime a cap (Jarrow), such a deal!  

Edited by synesthesia, 09 February 2016 - 05:17 AM.

[mikeinnaples]

That being said, if I developed cancer I would try a multi-factorial approach, including some "natural" stuff, and fasting.

 

I would add keto with hyperbaric oxygen therapy as well to my list.

[message]

Does ip6 do anything for otherwise healthy people?

There's a pretty good list of benefits here: http://selfhacked.co...aging-compound/

(Phytic Acid another name for IP6)

• 3 1) Phytic Acid is an Anti-oxidant.
• 4 2) Phytic Acid Reduces Inflammation.
• 5 3) Phytic Acid Induces Autophagy
• 6 4) Phytic Acid Has Potential For Treating Multiple Cancers
• 7 5) Phytic Acid Benefits Blood Glucose Control
• 8 6) Phytic Acid is Neuroprotective
• 9 7) Phytic Acid Reduces Triglycerides and Increases HDL
• 10 8) Phytic Acid Repairs DNA
• 11 9) Phytic Acid Increases Bone Mineral Density
• 12 10) Phytic acid protects human skin from UVB exposure
• 13 11) Phytic Acid Can Protect The Gut From Toxins
• 14 12) Phytic Acid Helps Prevent Kidney Stones
• 15 13) Phytic acid binds to Heavy Metals, Mycotoxins, Uranium, Iron, Manganese
• 16 14) Phytic Acid Decreases Uric Acid/Helps Gout
• 17 15) Phytic Acid is Anti-HIV
• 18 16) Phytic Acid Increases The Bioavailability of Flavones

Just one cap/day taken on a very empty stomach with plain water is all you need for prophylaxis, and at a dime a cap (Jarrow), such a deal!

Nice. Thanks for the links. Come to find out I had some ip6 from Jarrow lying around. I started taking one tab daily AM on empty stomach.

I haven't found anything but is there any contraindication to taking ip6 if I'm trying to get my wife pregnant?

[Dorian Grey]

One of the remarkable things about IP6 is its safety record.  Some were worried IP6 taken regularly or at high doses might damage bones due to mineral chelation, but the opposite turned out to be true.  Cancer patients take IP6 up to 8 times a day without any known issues appearing that I have found.  

 

I assume large amounts taken regularly with meals might cause mineral deficiencies, but taken properly on an empty stomach, I've seen no reported cautions.  

 

Pregnancy issues are tricky, and for women it's always wise to avoid supplements without a long track record of safety during pregnancy.  I can't imagine how IP6 might affect sperm quality, and the DNA/genetic repair qualities might actually be beneficial.  This said, I really don't know.  

 

Phytic Acid is found in substantial amounts in remarkably healthy foods like oatmeal and brown rice, so I would imagine these foods would have developed a history of pregnancy related issues if they contributed to problems during pregnancy.  

 

The only issue I can imagine might be if you were unfortunate enough to have a child with birth defects.  Some doctors like to blame supplements on this type of thing and you might be left wondering if any connection was possible for a very long time.  Spouses can sometimes play the blame game too.  For this reason, I imagine it might be best to avoid any possibility of this type of issue by avoiding anything that might be controversial as you work on producing a healthy offspring.  

 

IP6 is probably most helpful as we age, and you can certainly afford to be without it during this brief window of conception.  

[joelcairo]

Some epigenetic drugs are contraindicated for men, not just women, who might have children in the near future. A quick 1-minute search in Google did indeed bring up studies suggesting that some of IP6's benefits are due to epigenetic effects. The same applies to a variety of flavonoids, which we are also now discovering to cause epigenetic changes.

 

PROBABLY there would be no negative consequences as these things are not likely to be as potent as pharmaceutical drugs, but there's no harm in sticking to a normal healthy diet until you're done with that.

Edited by joelcairo, 15 February 2016 - 05:02 AM.

[Jesuisfort]

Bullshit,  Metformin, Rapamycin, resveratrol ,  + plenty of immunomodulator /booster can effectively prevent cancer