for those whose cancers have become resistant to chemotherapies...

[Lani]

more hopeful results on the major metabolite in curcumin--it seems to work on all three of the major drug transporters which have been found to mediate drug-resistance (they pump the drug out of the cancer cells so it goes back to poisoning the rest of the body , leaving the cancer cells happily multiplying free of the poison):

The cell line used was an ER+ her- cell line, but these three drug transporters which cause resistance to chemo seem to be very similar between many different types of cancer from what I have read.


Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin.

Limtrakul P,
Chearwae W,
Shukla S,
Phisalphong C,
Ambudkar SV.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Many studies have been performed with the aim of developing effective resistance modulators to overcome the multidrug resistance (MDR) of human cancers. Potent MDR modulators are being investigated in clinical trials. Many current studies are focused on dietary herbs due to the fact that these have been used for centuries without producing any harmful side effects. In this study, the effect of tetrahydrocurcumin (THC) on three ABC drug transporter proteins, P-glycoprotein (P-gp or ABCB1), mitoxantrone resistance protein (MXR or ABCG2) and multidrug resistance protein 1 (MRP1 or ABCC1) was investigated, to assess whether an ultimate metabolite form of curcuminoids (THC) is able to modulate MDR in cancer cells. Two different types of cell lines were used for P-gp study, human cervical carcinoma KB-3-1 (wild type) and KB-V-1 and human breast cancer MCF-7 (wild type) and MCF-7 MDR, whereas, pcDNA3.1 and pcDNA3.1-MRP1 transfected HEK 293 and MXR overexpressing MCF7AdrVp3000 or MCF7FL1000 and its parental MCF-7 were used for MRP1 and MXR study, respectively. We report here for the first time that THC is able to inhibit the function of P-gp, MXR and MRP1. The results of flow cytometry assay indicated that THC is able to inhibit the function of P-gp and thereby significantly increase the accumulation of rhodamine and calcein AM in KB-V-1 cells. The result was confirmed by the effect of THC on [(3)H]-vinblastine accumulation and efflux in MCF-7 and MCF-7MDR. THC significantly increased the accumulation and inhibited the efflux of [(3)H]-vinblastine in MCF-7 MDR in a concentration-dependent manner. This effect was not found in wild type MCF-7 cell line. The interaction of THC with the P-gp molecule was clearly indicated by ATPase assay and photoaffinity labeling of P-gp with transport substrate. THC stimulated P-gp ATPase activity and inhibited the incorporation of [(125)I]-iodoarylazidoprazosin (IAAP) into P-gp in a concentration-dependent manner. The binding of [(125)I]-IAAP to MXR was also inhibited by THC suggesting that THC interacted with drug binding site of the transporter. THC dose dependently inhibited the efflux of mitoxantrone and pheophorbide A from MXR expressing cells (MCF7AdrVp3000 and MCF7FL1000). Similarly with MRP1, the efflux of a fluorescent substrate calcein AM was inhibited effectively by THC thereby the accumulation of calcein was increased in MRP1-HEK 293 and not its parental pcDNA3.1-HEK 293 cells. The MDR reversing properties of THC on P-gp, MRP1, and MXR were determined by MTT assay. THC significantly increased the sensitivity of vinblastine, mitoxantrone and etoposide in drug resistance KB-V-1, MCF7AdrVp3000 and MRP1-HEK 293 cells, respectively. This effect was not found in respective drug sensitive parental cell lines. Taken together, this study clearly showed that THC inhibits the efflux function of P-gp, MXR and MRP1 and it is able to extend the MDR reversing activity of curcuminoids in vivo.
PMID: 16960658 [PubMed - as supplied by publisher]

[Sandy H]

Lani, thanks for this info but I didn't understand much of it. Sounds as though its written more for the professionals, oncologist and researchers. Please don't tell me to look any of this up because it wouldn't help. I hope some here were able to understand it. Sandy

[Vanessa]

My oncologist stated that they are doing research on turmeric at M.D. Anderson with promising results. She said it was fine to take it in capsule form and assured me that it would not interfere with my chemo. I am glad to hear there is more good news about turmeric. I had a hard time understanding the article also, but I got the main idea that turmeric is a good thing. Thanks.

[chrisy]

Lani,

Thanks for this post, as well as your intro! This is really exciting news; both the helpful impact on resistance AND the fact that somebody is actually testing this stuff!

Gotta go take my curcumin supplement now...
Chris

[Becky]

Lani


I read this awhile ago and it is exciting. I wished I knew it when I was on taxol. In the meantime, I have met women in the infusion center who are Stage 4 getting taxotere and herceptin and I tell them to have curried "something" the day before chemo and to make enough to have it the day of chemo and the next day. I am hesitant to tell them to take the capsules (which I do myself now) because so MANY are SO uninformed and they are told to take absolutely no supplements. I cannot take it upon myself to tell them to do so but at least eating it naturally is fine and none of the oncs there will come down on me.

I always, from the beginning, tried to be as informed as possible and you and others on this board have personally helped me tremendously. The more I learn and know the more I am amazed at what other HER2+ women (with mets no less) don't know. I always tell them to get their brain MRI and they say that their doctor didn't tell them to get one. Bizzare (and obviously one of those doctors is my doctor). One woman said she thought it was a good idea (because I explained why) but if her doctor (one I switched from quite some time ago) didn't say - what should she do. I told her to just tell him she wanted one (and she did and is getting one next week).

Thanks for all the good info some of which I haven't found myself.

Kind regards

Becky

[sarah]

don't forget to take it with food.

[sharonf]

This is exciting information, but there was another study (back in 2002) which shows that "Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer." Which one should we go with? (though I tend to believe that curcumin will do more good than harm)

Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer.


Somasundaram S (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Somasundaram+S%22%5BAuthor%5D),
Edmund NA (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Edmund+NA%22%5BAuthor%5D),
Moore DT (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Moore+DT%22%5BAuthor%5D),
Small GW (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Small+GW%22%5BAuthor%5D),
Shi YY (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Shi+YY%22%5BAuthor%5D),
Orlowski RZ (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_AbstractPlus&term=%22Orlowski+RZ%22%5BAuthor%5D).
The Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.

Curcumin, the major component of the spice turmeric, is used as a coloring and flavoring additive in many foods and has attracted interest because of its anti-inflammatory and chemopreventive activities. However, this agent also inhibits the generation of reactive oxygen species (ROS) and the c-Jun NH(2)-terminal kinase (JNK) pathway, and because many chemotherapeutic drugs generate ROS and activate JNK in the course of inducing apoptosis, we considered the possibility that curcumin might antagonize their antitumor efficacy. Studies in tissue culture revealed that curcumin inhibited camptothecin-, mechlorethamine-, and doxorubicin-induced apoptosis of MCF-7, MDA-MB-231, and BT-474 human breast cancer cells by up to 70%. Inhibition of programmed cell death was time and concentration dependent, but occurred after relatively brief 3-h exposures, or at curcumin concentrations of 1 microM that have been documented in Phase I chemoprevention trials. Under these conditions, curcumin exhibited antioxidant properties and inhibited both JNK activation and mitochondrial release of cytochrome c in a concentration-dependent manner. Using an in vivo model of human breast cancer, dietary supplementation with curcumin was found to significantly inhibit cyclophosphamide-induced tumor regression. Such dietary supplementation was accompanied by a decrease in the activation of apoptosis by cyclophosphamide, as well as decreased JNK activation. These findings support the hypothesis that dietary curcumin can inhibit chemotherapy-induced apoptosis through inhibition of ROS generation and blockade of JNK function, and suggest that additional studies are needed to determine whether breast cancer patients undergoing chemotherapy should avoid curcumin supplementation, and possibly even limit their exposure to curcumin-containing foods.

PMID: 12097302 [PubMed - indexed for MEDLINE]

[vickie h]

Lani, which brand of curcurmin do you take and how much. You sound alot like me, always staying pro-active. I switched Oncologists because mine wasn't doing what I had learned was necessary, and I love my Onc now. We need to stay alert and be apart of our treatment and healing. thanks for the info. Hugs, Vickie H

[julierene]

I have tried both of these and they both upset my stomach even with food. I can't stand the taste of it on my food either. Are there some recipes that have a lot of the spices, that don't taste like it? Fat chance right?

[chrisy]

Sharon,
Interesting post - I had not seen this study. I would interpret this as you should avoid curcumin when taking chemos that act on these pathways. But that chemos that act in other ways would be ok or possibly synergystic as some other studies have suggested. I'm certainly no expert, but I'd definitely confirm what chemo drugs would be ok to supplement with curcumin.

Seems there are few perfect solutions, and it's definitely a challenge, for me anyway, to balance the apparent conflicting information

[Karen t]

I ordered the Super Curcumin from LifeExtension and when I received it the warning on the bottle says: Do not take with anticancer drugs. Since I'm on Herceptin and Navelbine, I didn't know what to do. Advice?

[Lani]

is noone has done the scientific studies to determine exactly how much one should take.

Many "drugs" (chemical or biologic compounds that have a beneficial effect when used in humans/animals) have different effects depending on what concentration they are used in. And some have different effects on animals than on people, as animals livers and kidneys metabolize them differently.

I do not know the answer to your question and have not found any literature answering your question--but promise to keep looking!