9 replies to this topic

[Dolph]

http://www.ncbi.nlm....pubmed/23298290

Edited by Dolph, 10 January 2013 - 10:21 AM.

[maxwatt]

How about mice with a normal healthy immune system?

Other studies have shown resveratrol increases migratory behavior of mammary cancer cells, but at doses that also induce apoptosis.

[cudBwrong]

How about mice with a normal healthy immune system?

Other studies have shown resveratrol increases migratory behavior of mammary cancer cells, but at doses that also induce apoptosis.

maxwatt is asking the right question, but there is no easy way to answer it.

This study deserves more attention. There are a very large number of studies which show some sort of protective effect of resveratrol and cancer, but this study shows a harmful effect. This is important as we evaluate whether cancer patients should be given resveratrol in clinical trials.

Consider what they are trying to investigate here: they are trying to move from the test tube to the live mammal. Test tube (in vitro) studies show that resveratrol inhibits the growth of various flavors of cancer cells. Does this work in a live animal?

The problem is that in many cases when you try to introduce cancer cells from a known "cell line," growing in a test tube, into a living animal, the animal's immune system attacks the foreign cancer cells and destroys them. It's hard to separate the effect of your therapeutic agent from the effect of the animal's immune system.

The solution used here, as in many studies, is to use an experimental animal with a damaged immune system. Here it is an SCID mouse, Severely Compromised, Immuno-Deficient.

In this study, tumor cells were introduced into these mice; some were given resveratrol, some were not. The tumors in the mice with resveratrol grew much faster, and spread to more locations. The more resveratrol, the more the tumors grew. I guess it was good for them!

The unanswered question is whether this phenomenon happens with an animal with a more normal immune system. There are many studies, as I say, that show an opposite effect.

The question is important, especially when we consider that patients who receive chemotherapy or radiation may have weak immune systems, at least temporarily.

Edited by cudBwrong, 17 May 2013 - 12:09 PM.

[zorba990]

Food form versus isolate seems better

Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols.
http://www.ncbi.nlm....3298290/related
http://www.ncbi.nlm....9294520/related

Edited by zorba990, 17 May 2013 - 04:47 PM.

[cudBwrong]

Food form versus isolate seems better

Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols.
http://www.ncbi.nlm....3298290/related
http://www.ncbi.nlm....9294520/related

These are interesting results. One feature that stands out for me is that they are using a different kind of mouse. I believe that these animals do not have the same level of immune deficiency as the SCID mice in the study linked in the original post.

[hav]

Sounds like the study supports the idea that if you have breast cancer and are receiving a treatment that suppresses your immune system, you probably shouldn't take resveratrol at the same time. But I imagine they wouldn't want you to take any antioxidants. Probably not alcoholic beverages either.

Noticed this regarding the diet the mice were on:

Hairless SCID or athymic nu/nu female mice were orally gavaged either with vehicle (90% neobee oil, 10% ethanol), or 0.5, 5, or 50 mg/kg body weight (BW) resveratrol in a 100 μL volume every day (5 days/wk).

Neobee oil sounds like its an MCT oil. Combined with ethanol, it probably insures express resveratrol delivery directly to the liver with rapid energy release from the vehicle carriers. Makes me wonder if a long chain triglyceride carrier like olive oil might have yielded very different results.

Also didn't see any description of how they did the actual mixing of the resveratrol with the oil. Could explain the results if they heated or sonicated it. Here's a study about cooking with coconut milk which is high in mct fats:

Method of cooking and risk of breast cancer in the Philippines

Boiling food in coconut milk was associated with a significantly increased risk of breast cancer

Howard

Edited by hav, 21 May 2013 - 08:30 PM.

[cudBwrong]

Noticed this regarding the diet the mice were on:

Hairless SCID or athymic nu/nu female mice were orally gavaged either with vehicle (90% neobee oil, 10% ethanol), or 0.5, 5, or 50 mg/kg body weight (BW) resveratrol in a 100 μL volume every day (5 days/wk).

Neobee oil sounds like its an MCT oil. Combined with ethanol, it probably insures express resveratrol delivery directly to the liver with rapid energy release from the vehicle carriers. Makes me wonder if a long chain triglyceride carrier like olive oil might have yielded very different results.

Also didn't see any description of how they did the actual mixing of the resveratrol with the oil. Could explain the results if they heated or sonicated it. Here's a study about cooking with coconut milk which is high in mct fats:

Method of cooking and risk of breast cancer in the Philippines

Boiling food in coconut milk was associated with a significantly increased risk of breast cancer

Howard

I sent an inquiry to Professor Castillo-Pichardo, who was kind enough to respond. She says:

"We prepared resveratrol stocks in ethanol. Resveratrol dissolved in ethanol at the concentrations we used, so there was no need to apply heat or to sonicate. Then we mixed the stock solutions with neobee oil and vortexed it; the solutions we administered to the mice had 10% ethanol in neobee oil."

So it was not a confounding effect of heat or sonication of the medium chain triglycerides, which as Howard suggests, is either a primary, or the sole component of Neobee oil. However, this was quite a good suggestion, well worth following up.

Since the control animals received the same vehicle, the results show a differential of resveratrol plus mct / ethanol over mct / ethanol alone. Also, there is a dose /response relationship, where higher resveratrol promoted higher tumor growth. Note also that at the highest dose, the experiment terminates early because the animals could not survive the tumor load; in other words, the response is truncated at the top, as if there is no more room on top of the graph.

Edited by cudBwrong, 23 May 2013 - 07:27 PM.

[niner]

I don't want to just dismiss this paper, but I note that these were particular cancer cell lines that were implanted in the SCID mice. That's quite different than tumors that develop spontaneously from normal tissue.

[cudBwrong]

I don't want to just dismiss this paper, but I note that these were particular cancer cell lines that were implanted in the SCID mice. That's quite different than tumors that develop spontaneously from normal tissue.

This is quite true. It is a technique that is used often because it can be hard to wait around for tumors to develop spontaneously. Also, you know that the tumors in your experimental and control animals are genetically identical.

It's fascinating. I just took a look at one of the papers posted by zorba990, and I noticed that it is the same principal investigator, Linette Castillo Pichardo. In this study (free full text) :


www.ncbi.nlm.nih.gov/pmc/articles/PMC2898569

they get an opposite result, with similar methods. Same cell line, but, if I read this correctly, different mice.

Edited by cudBwrong, 23 May 2013 - 08:56 PM.

[hav]

I don't want to just dismiss this paper, but I note that these were particular cancer cell lines that were implanted in the SCID mice. That's quite different than tumors that develop spontaneously from normal tissue.

This is quite true. It is a technique that is used often because it can be hard to wait around for tumors to develop spontaneously. Also, you know that the tumors in your experimental and control animals are genetically identical.

It's fascinating. I just took a look at one of the papers posted by zorba990, and I noticed that it is the same principal investigator, Linette Castillo Pichardo. In this study (free full text) :


www.ncbi.nlm.nih.gov/pmc/articles/PMC2898569

they get an opposite result, with similar methods. Same cell line, but, if I read this correctly, different mice.

Looks like another difference is that they used corn oil instead of neobee in the earlier study that showed resveratrol (as well as quercertin and catechin) inhibiting mammary tumor growth.

Howard