Prozac, the Anti-depressant drug, Significantly Enhances the Efficacy of Chemotherapy
If you are on chemotherapy, you must send this essay to your oncologist.
In studies in both the US and Australia, the five year survival rate for 22 different cancers using chemotherapy alone is only about 2%.
http://grouppekurosawa.com/blog/2006/03/survival-advantage-of-chemotherapy-is
Although many chemotherapeutic drugs effectively kill cancer and leukemia cells in the short run, they usually fail over time. This failure can be attributed to the establishment of chemo drug resistance. This resistance takes many forms, but one of the most common form of resistance is the over expression of membrane pumps in cancer cells. These pumps act as a "revolving door" which pumps these drugs out of cancer cells as quickly as they enter. Unfortunately, normal cells do not over express these pumps which means that chemo drugs can accumulate and kill normal cells.
This form of multi-drug resistance can be overcome by the common anti-depressant drug Prozac (fluoxetine). Prozac enhances the toxicity of chemo drugs, such as doxorubicin, mitomycin C, vinblastine, paclitaxel (Taxol) by 10 to 100 times. This is a direct result of Prozac's ability to inhibit the activity of membrane pumps, thereby concentrating the chemo drugs in the cancer cells. The dosage of Prozac necessary to promote chemosensitivity is well below its known toxic levels.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15492283&itool=pubmed_docsum
In a mouse model, Avastin (bevacizumab), an inhibitor of VEGF, vascular endothelial growth factor, a known promotor of cancer cell growth and development, cannot compete with the simple combination of Prozac and doxorubicin in their efficacy to kill human colon cancers. While both Prozac (fluoxetine) and doxorubicin are both inexpensive generic drugs, Avastin cost $80,000 a year. If you don't have medical insurance, Avastin is not an option. Also, Avastin is a large monoclonal antibody that has difficulty penetrating into tumor masses. Prozac and doxorubicin are small molecules that will penetrate all tissues.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18851896&itool=pubmed_docsum
In the next essay, we will discuss additional anti-cancer properties of Prozac.
Stay tuned...
Grouppe Kurosawa, Medicine in the Public Interest
http://www.grouppekurosawa.com/
In studies in both the US and Australia, the five year survival rate for 22 different cancers using chemotherapy alone is only about 2%.
http://grouppekurosawa.com/blog/2006/03/survival-advantage-of-chemotherapy-is
Although many chemotherapeutic drugs effectively kill cancer and leukemia cells in the short run, they usually fail over time. This failure can be attributed to the establishment of chemo drug resistance. This resistance takes many forms, but one of the most common form of resistance is the over expression of membrane pumps in cancer cells. These pumps act as a "revolving door" which pumps these drugs out of cancer cells as quickly as they enter. Unfortunately, normal cells do not over express these pumps which means that chemo drugs can accumulate and kill normal cells.
This form of multi-drug resistance can be overcome by the common anti-depressant drug Prozac (fluoxetine). Prozac enhances the toxicity of chemo drugs, such as doxorubicin, mitomycin C, vinblastine, paclitaxel (Taxol) by 10 to 100 times. This is a direct result of Prozac's ability to inhibit the activity of membrane pumps, thereby concentrating the chemo drugs in the cancer cells. The dosage of Prozac necessary to promote chemosensitivity is well below its known toxic levels.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15492283&itool=pubmed_docsum
In a mouse model, Avastin (bevacizumab), an inhibitor of VEGF, vascular endothelial growth factor, a known promotor of cancer cell growth and development, cannot compete with the simple combination of Prozac and doxorubicin in their efficacy to kill human colon cancers. While both Prozac (fluoxetine) and doxorubicin are both inexpensive generic drugs, Avastin cost $80,000 a year. If you don't have medical insurance, Avastin is not an option. Also, Avastin is a large monoclonal antibody that has difficulty penetrating into tumor masses. Prozac and doxorubicin are small molecules that will penetrate all tissues.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=18851896&itool=pubmed_docsum
In the next essay, we will discuss additional anti-cancer properties of Prozac.
Stay tuned...
Grouppe Kurosawa, Medicine in the Public Interest
http://www.grouppekurosawa.com/
posted by Dr. Steve at 10:20 AM
15 Comments:
Thanks Dr. Martin for addressing the Prozac issue, now I wonder if prozac would help keep cancer from metastasizing??? Jean
Good question. Yes I believe it would because Prozac also activates cell mediated immunity by blocking psychological stress induced immunosuppression.
This paper (stunning, it's from 2004 and there's not a single tral I can find!) is amazing in the results it gets around P-glucoprotein pumps (Pgp). There are also a set of at least 8 multidrug resistance proteins (MRP1 - MRP8) and some of these are known to be involved in chemo drug resistance, at least MRP1 is. Are there any good ways to deal with these ATP pumps?
There are many natural products like Honokiol that work on various MRPs and other resistance factors. I think Genestein and Curcumin both downregulate MDR.
You have to be careful though, once Celebrex was though to prevent MDR, and it did...somewhat. It downregulated some of the MRPs, but unfortunately, it upregulated others, I think (MRP4 and MRP5) which is why it failed miserably in clinical trials for colon cancer.
That being said, Prozac looks very promising...
Interesting. Do you know of any information I could read up on regarding inhibition of MRP1 and LRP?
Thanks.
There are some good studies on MDR out there that I have read, but I can't recall them off the top of my head. I think it really depends on what type of cancer you have. Different cancers express different MDR profiles. Some MRPs are active in some cancers and not others.
Just use Google Scholar and research MDR and your particular type of cancer. Search each one of the MRPs, p-glycoprotein along with other factors like CHK-1 and CHK-2 to see what applies in your situation. It can be frustrating though, because there are so many things that can lead to MDR.
I assume that is why products like Methyl Jasmonate are so good. They can kill resistant cancer cells because their mode of action (ATP depletion) doesn't suffer the same drawbacks as chemo.
Thanks, yes, I've been trying to do that. Regrettably, I have a rare sodt-tissue sarcoma so it's hard to find good information.
A poster sessionin a 1999 conference says that large number of tumors express LRP (almost 90%), while MRP1 and Pgp are much less expressed. I also see a bit of mention of GST-pi as common and corrleated with MDR in soft tissue as well as osteo sarcomas.
I take your point about MJ, but I question whether it's a good stand alone treatment, especially for sarcomas. I base this mostly on one paper: http://www.ncbi.nlm.nih.gov/pubmed/18953440?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Ah...I see.
Well, I'm no doctor, though I play one on the Internet. Dr. Martin would be the best person to direct questions about MJ to.
Interestingly enough, the glycolysis inhibitor (2-DG) that was used in that study is no longer being pursued by the manufacturer...I guess it wasn't profitable enough.
There is a better glycolysis inhibitor that is being developed by a Dr. Ko formerly from John's Hopkins. It's called 3-bromopyruvate. Dr. Martin has blogged about 3-brp in the past. Look it up, it has had dramatic positive results in the lab.
Dr. Ko has recently developed a 3-brp composition that's safe for human use and supposedly it will be available soon for use in clinical trials.
Until then you can take a look at her work for yourself if you're interested.
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220070203074%22.PGNR.&OS=DN/20070203074&RS=DN/20070203074
Yes, I'm familiar with 3-bromopyruvate having stumbled on the JH researcha while back. Hopefully something will come of it soon. It would also be nice to find naturally occuring glycolysis inhibitors.
Thanks for your comments.
I just found a really interesting study stating that the use of Sodium Bicarbonate can help reduce Multidrug Resistance.
Apparently, pH gradients between what's going on outside a tumor cell (high pH) and what is going on inside the a tumor cell (low pH) can contribute to MDR.
A lot of chemo drugs are weakly basic and may get sequestered and pumped out, or neutralized once in the tumor. Sodium bicarbonate "evens out" this pH gradient may reverse/inhibit MDR.
http://www.cancer-therapy.org/volume6_2008/06_Iessi/06._Iessi_et_al,_55-66.pdf
http://www3.interscience.wiley.com/cgi-bin/summary/105558961/SUMMARY?CRETRY=1&SRETRY=0
So, SB may actually work against cancer, but it probably has NOTHING to do with cancer being a fungus.
I was intrigued by the comment about Methyl Jasmonate and sarcomas.
We know that Methyl Jasmonate interferes with glycolysis. So do 3-bromopyruvate and 2-DG.
Several studies have stated that inhibition of HIF-1, Akt and mTOR sensitize cancer cells to these glycolysis inhibitors.
http://mct.aacrjournals.org/cgi/content/abstract/7/6/1506
So, with that being said, I think that you're right, that the efficacy of Methyl Jasmonate can certainly be increased by inhibiting certain pathways and such.
So, I guess a good question is what would you use to inhibit the PI3K/Akt/mTOR pathway?
I've done a bunch of studies on this survival pathway and it keeps coming up, over and over, with all sorts of cancers. It seems like inhibiting PI3K would be a major part of a successful protocol.
One other thing:
Dr. Ko seems to be at JH again, at least she is in their directory, listed as a non-employee.
She was one of three authors on a new paper about 3-bromopyruvate, along with Dr. Pedersen. I can't find the link now but it's easy to find on pubmed. I don't know if there's much new in it because I only had access to the abstract.
Maybe they've sorted out the mess there.
High levels of Glutamine inhibits both mTor and AKT. I will discuss the glutamine AKT connection very soon.
A Washington DC physician once told me that if you have cancer you go to Johns Hopkins to die. Their arrogance is unbelievable. Ted Kennedy's daughter was being treated by JH for cancer and doing poorly so he pulled her out and sent her to Mass General Hospital for treatment. She recovered.
Fortunately I've only been to DFCI, MSKCC and now MGH.
I've done some research on IP6 (I know, not your favorite substance) with respect to PI3K inhibition.
I think this paper is actually pretty useful: http://www.fasebj.org/cgi/content/full/14/9/1179?ijkey=bf3616716cefd0c7e3ae709be56749ab34a6141e
There's also a follow on here: http://cancerres.aacrjournals.org/cgi/content/full/65/18/8339
All full text available. What these indicate is that IP6 isn't very useful on it's own but it is available in cells despite the thoughts to the contrary.
However Inositol pentakiphosphate is very active inhibiting PI3K. The problem is that getting the latter from IP6 happens at very, very low yeild which may account for the large amounts of IP6 needed to be active.
Now, if we could find a way to make Inositol pentakiphosphate from IP6, that would seem like a good idea. I've looked around and I don't think anyone sells such a supplement. I suppose that since it's a natural component of foods (see: http://www.ncbi.nlm.nih.gov/pubmed/15264889?dopt=Abstract) it wouldn't have as many problems at the FDA as wholly synthetic compounds.
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