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...
