Metformin and Valproic Acid Has a Greater Anti-tumoral Effect on PCa Growth In Vivo than Either Drug Alone.

[pjoshea13]

New mouse study below [1].

From Wikipedia [2]:

"Valproate (VPA), and its valproic acid, sodium valproate, and valproate semisodium forms, are medications primarily used to treat epilepsy and bipolar disorder and to prevent migraine headaches."

"Valproate was first made in 1881 and came into medical use in 1962. Valproate is included in the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is between 0.14 and 0.52 USD per day. In the United States, it costs roughly $0.90 USD per day."

"The medication has been tested in the treatment of ... cancer, owing to its histone deacetylase-inhibiting effects." [3]

One of the ways in which cancer suppresses anti-cancer genes, is epigenetically by preventing access. DNA it tightly wound around proteins called histones. Access requires acetylation of the relevant histones, which loosens things up. PCa counters with histone deacetylase [HDAC]. Valproic acid [VPA] inhibits HDAC.

Just why Metformin & VPA would have synergy, I don't know.

"In both LNCaP and PC-3 xenografts, MET combined with VPA significantly reduced tumor growth during the first 4 weeks following treatment, and delayed the time-to-tumor volume of 2,000 mm3 by 90 days, as compared to MET or to VPA alone, and to vehicle control."

I wrote about VPA 2 years ago [4]:

"Non-PCa Prescription Drugs: Valproic Acid / Valproate"

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/305...

In Vivo. 2019 Jan-Feb;33(1):99-108. doi: 10.21873/invivo.11445.

The Combination of Metformin and Valproic Acid Has a Greater Anti-tumoral Effect on Prostate Cancer Growth In Vivo than Either Drug Alone.

Tran LNK1,2, Kichenadasse G3, Morel KL3, Lavranos TC4, Klebe S5, Lower KM6, Ormsby RJ3, Elliot DJ7, Sykes PJ3.

Author information

Abstract

BACKGROUND/AIM:

The hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA) have individually shown anti-tumor effects in prostate cancer in vitro. The present study intended to investigate the efficacy of the combination of MET and VPA in prostate cancer treatment in a pre-clinical xenograft model.

MATERIALS AND METHODS:

Prostate cancer cell lines (LNCaP and PC-3) were inoculated under the skin of BALB/c nude mice. The mice were treated with 200 μl/ml MET and/or 0.4% (w/v) VPA diluted in drinking water, or with vehicle control, and were monitored until the tumor volume reached 2,000 mm3 Evaluation of toxicity of the drug combination was determined in liver and kidney by histology.

RESULTS:

In both LNCaP and PC-3 xenografts, MET combined with VPA significantly reduced tumor growth during the first 4 weeks following treatment, and delayed the time-to-tumor volume of 2,000 mm3 by 90 days, as compared to MET or to VPA alone, and to vehicle control. There was no significant difference in total mouse weight, liver or kidney morphology in response to combination treatment (MET+VPA) compared to MET or VPA alone and vehicle control.

CONCLUSION:

The combination treatment of MET with VPA is more effective at slowing prostate tumor growth in vivo compared to either drug alone, in mouse xenografts. These pre-clinical results support previous in vitro data and also demonstrate the low toxicity of the combination of these drugs, suggesting that this may be a potential new therapy to be investigated in clinical trials for prostate cancer.

Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

KEYWORDS:

Metformin; nude mice; prostate cancer chemotherapy; valproic acid; xenograft

PMID: 30587609 DOI: 10.21873/invivo.11445

***

[2] en.wikipedia.org/wiki/Valpr...

[3] en.wikipedia.org/wiki/Histo...

[4] healthunlocked.com/advanced...

[NPfisherman]

Patrick...you continue to provide solid posts and at this rate, my MO visit in January may take 3 hours with all the questions...Hope he doesn't cry or transfer me to a colleague..

All the best,

Fish

[Hidden]

Hi Patrick,

My MO is strictly a standard based treatment practitioner, any recommendations on getting prescriptions?

I've recently added an internal medicine physician, perhaps can discuss this and see what happens...

[pjoshea13 in reply to Hidden]

I approached my integrative medicine guy by email 13 years ago. The issue for me was that I was using androstenedione to raise testosterone [T]. Not much point in having a consultation with someone who might refuse to treat me. How many office visits would I have to pay for before I found a sympathetic doc?

Anyway, my first choice had no problem at all. I didn't go into our first meeting with a shopping list. My strategy was to not be pushy & show that I knew a lot about the disease & my situation. The first script was his suggestion - Arimidex to replace the chrysin I was using.

When I was running low on andro (it had been banned by then) I asked for a T prescription. He was OK with that.

After a while I got Metformin (low dose). Subsequently, 2,000 mg/day.

Later, nitroglycerine patches.

Recently Minocycline.

As the years go by, I think he has become very comfortable with me requesting stuff. How would he react to Valproic Acid? I don't know, but will ask for his thoughts next time.

At this stage, my other doc says that all I have to do is ask for somrthing & he would write it for me.

I think I am lucky with my doctors, but the key, I believe, is to go slowly & show that you know your stuff.

-Patrick

[tennis4life in reply to Hidden]

NY Mets, I added the metabolic approach to my supplement regime and used Care Oncology (800-392-1353). They will prescribe metformin, atorvastatin, and alternating doses of mebendazole one month and doxycycline for one month. Only problem with this outfit is the upfront cost of the initial DR consultation which is $ 800.00. Aside from the prescriptions, I also wanted to investigate the organization as a resource so bit the bullet and dove in. The program is usually in addition to standard of care treatment being given to the patient. I'll be posting my results after about 3 - 4 months on the program.

[jdm3 in reply to tennis4life]

Thanks for this info. I have been interested in the Care Oncology protocol and will interested to read your updates. All the best for a healthy new year, Josh

[Hidden in reply to tennis4life]

I second that, going to call them, the $800.00 is steep, but I've spent more on headphones, so...

Thank you very much for the info!