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Old 09-09-2006, 08:09 AM   #1
Lani
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for those whose cancers have become resistant to chemotherapies...

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]
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Old 09-09-2006, 10:15 AM   #2
Sandy H
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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
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Old 09-09-2006, 07:33 PM   #3
Vanessa
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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.
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Old 09-09-2006, 10:03 PM   #4
chrisy
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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
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June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial

5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
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Old 09-10-2006, 08:52 AM   #5
Becky
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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
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Old 09-11-2006, 08:14 AM   #6
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don't forget to take it with food.
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