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TreasureVibe
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I drank my first full mug of sodium bicarbonate mixed with ACV. It was a big mug and filled almost to the top with tap water. Put in 2 well-filled tablespoons of ACV and afterwards a pretty heap of 1/2th teaspoon baking soda. The baking soda was a bit old, and depending on how the best by date is put (I can't tell) it's either past its expiration date in either april or august this year. So it might not have reacted as strongly with the ACV as it normally would. Anyways, there was still fizzing, and bubbles going up. I noticed how the strains of the mother of the ACV I was using rose up to the top of the water directly after putting in the baking soda. Stirring the glass with a plastic spoon made it fizz even more after it had quit fizzing after about 12 seconds. I used Braggs ACV.
I drank it and I noticed it tasted alkaline, with only a scent of ACV I could smell while in my mouth, not actually taste. I normally really like the soury taste of ACV in water, so this was something different. After taking it, I noticed pain relief in my right shoulder and lung, where I've always had a cough and pain for 2 years now. Also internal congestion inside the lung felt like it was dissolving, and things were going down there I felt. I also felt a bit more energetic, and a bit more clarity. Breathing also feels more pleasant, and this stiffness of my right shoulder also seems to dissapear somewhat. All in all this first glass was a success and I plan on doing it more. I think I put in a bit too much baking soda, I will try a bit fewer the next time.
I actually wonder, what is the significance of the pH of the solution we're making, is there actually any? You might as well just buy potassium acetate and sodium acetate, put it in water and drink it up. Unreacted bicarbonate I might add, does aid the kidneys (the kidneys naturally produce their own bicarbonate), and if it produces CO2 in the body that's also a benefit. But drinking only ACV will give you potassium acetate as well so I wonder why Ted put baking soda with it, or I've might missed an explanation. If so, please excuse me! Also the alkaline pH could aid pathogens, so unless there's a specific reason for it, I think trying just potassium acetate powder and maybe sodium acetate powder could be worth it too for specific diseases, like cancer perhaps. Ted did mention that acidic substances like for example ascorbic acid, caused voltage of cells to become unhealthier and cause cancer though so that could be the reason! The common occurrence of both baking soda and apple cider vinegar in households and in local supermarkets/general stores is however quite a convenience, for its quick, cheap and easy access to make a ACV/BS solution.
I really like what this is doing to my body, and I do recommend it! Will be using it again, and report back.
I am also wondering how the voltage of the cancer cell theory and its dynamics fits in with Ray Peat's recommendation of 1500-2000 mg of dietary calcium daily, and what calcium acetate could mean for health. Ray Peat recommends eggshell calcium, and it's popular among people to make calcium acetate by reacting the eggshell calcium with apple cider vinegar.
I also happened to come across these six significant studies:
Effect of sodium acetate on cell proliferation and induction of proinflammatory cytokines: a preliminary evaluation.
Food Chem Toxicol. 2005 Dec;43(12):1773-80.
Sun J1, Bi L, Chi Y, Aoki K, Misumi J.
Inner Mongolia Medical College, Huhehaote City, Inner Mongolia, China. [email protected]
Abstract
We have studied the effect of sodium acetate exposure on the viability and proliferative activity of cultured human gastric adenocarcinoma epithelial (AGS) cells and changes in the release of proinflammatory cytokines. We evaluated the levels of IL-6, TNF-alpha, IL-8, and IL-1beta in cell culture supernatants using enzyme-linked immunosorbent assays, and cytokine mRNA levels were measured in whole cells using reverse transcriptase-polymerase chain reaction. We also measured cytokine levels in mice using immunohistochemistry. In vitro studies demonstrated that incubation with sodium acetate (up to 12.5 mM) for 72 h stimulated AGS cell viability and proliferation in a dose-dependent manner; however, incubation with >12.5 mM sodium acetate inhibited cell growth, also in a dose-dependent manner (the largest decrease in viability was >50%). Incubation with sodium acetate for 24 h increased the levels of IL-1beta, IL-8, and TNF-alpha protein and mRNAs (IL-6 was detected but its mRNA was not). The effect of sodium acetate on the expression of these cytokines in cell culture was verified in mice. Our data suggest that ingestion of high concentrations of sodium acetate in food has cytotoxic effects.
Source: Effect of sodium acetate on cell proliferation and induction of proinflammatory cytokines: a preliminary evaluation. - PubMed - NCBI
Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release
Published: 21 February 2013
Cell Death & Disease volume 4, page e507 (2013)
C Marques, C S F Oliveira, S Alves, S R Chaves, O P Coutinho, M Côrte-Real & A Preto
Abstract
Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortality. Short-chain fatty acids secreted by dietary propionibacteria from the intestine, such as acetate, induce apoptosis in CRC cells and may therefore be relevant in CRC prevention and therapy. We previously reported that acetic acid-induced apoptosis in Saccharomyces cerevisiae cells involves partial vacuole permeabilization and release of Pep4p, the yeast cathepsin D (CatD), which has a protective role in this process. In cancer cells, lysosomes have emerged as key players in apoptosis through selective lysosomal membrane permeabilization (LMP) and release of cathepsins. However, the role of CatD in CRC survival is controversial and has not been assessed in response to acetate. We aimed to ascertain whether LMP and CatD are involved in acetate-induced apoptosis in CRC cells. We showed that acetate per se inhibits proliferation and induces apoptosis. More importantly, we uncovered that acetate triggers LMP and CatD release to the cytosol. Pepstatin A (a CatD inhibitor) but not E64d (a cathepsin B and L inhibitor) increased acetate-induced apoptosis of CRC cells, suggesting that CatD has a protective role in this process. Our data indicate that acetate induces LMP and subsequent release of CatD in CRC cells undergoing apoptosis, and suggest exploiting novel strategies using acetate as a prevention/therapeutic agent in CRC, through simultaneous treatment with CatD inhibitors.
Source: https://www.nature.com/articles/cddis201329
Apoptotic effect of sodium acetate on a human gastric adenocarcinoma epithelial cell line
Genet. Mol. Res. 15 (4): gmr.15048375 Published October 5, 2016
DOI http://dx.doi.org/10.4238/gmr.15048375
Y. Xia1 *, X.L. Zhang2 *, F. Jin3 *, Q.X. Wang1 , R. Xiao1 , Z.H. Hao4 , Q.D. Gui5 and J. Sun1
1 Inner Mongolia Medical University, Hohhot, China 2 Capital Medical University, Beijing, China 3 Inner Mongolia Vocational College of Chemical Engineering, Hohhot, China 4 Inner Mongolia People’s Hospital, Hohhot, China 5 International Mongolia Hospital of Inner Mongolia, China
ABSTRACT
The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.
Source: http://www.funpecrp.com.br/gmr/year2016/vol15-4/pdf/gmr8375.pdf
Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Published: November 20, 2013 Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Patrick M. Long, Scott W. Tighe, Heather E. Driscoll, John R. Moffett, Aryan M. A. Namboodiri, Mariano S. Viapiano, Sean E. Lawler, Diane M. Jaworski
Research article - Peer-reviewed
Abstract
Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation.
Source: Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Triacetin‐based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma
Cancer Cell Biology
First published: 30 August 2013 https://doi.org/10.1002/ijc.28465
Andrew R. Tsen Patrick M. Long Heather E. Driscoll Matthew T. Davies Benjamin A. Teasdale Paul L. Penar William W. Pendlebury Jeffrey L. Spees Sean E. Lawler Mariano S. Viapiano Diane M. Jaworski
Abstract
Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N‐acetyl‐l‐aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth‐inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor‐derived glioma stem‐like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli‐Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA‐induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA‐mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors.
Source: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.28465
Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules
British Journal of Cancer (2001) 84(6), 802–807 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1648
M Vasse1, D Thibout2, J Paysant1, E Legrand1, C Soria1,3 and M Crépin2
1Laboratoire DIFEMA, Groupe de Recherche MERCI, Faculté de Médecine et Pharmacie de Rouen, 22 Bd Gambetta, 76183 Rouen Cedex, France; 2UPRES 2360, équipe d’Oncologie Cellulaire et Moléculaire, SMBH Université de Paris 13, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France; 3U353, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Summary
Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDAMB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDAMB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1. © 2001 Cancer Research Campaign http://www.bjcancer.com
Source: http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2363819&blobtype=pdf
Also several interesting, related studies: ATP citrate lyase inhibition can suppress tumor cell growth, ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation,
An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis,
Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments. - PubMed - NCBI, ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch, Dichloroacetate shifts the metabolism from glycolysis to glucose oxidation and exhibits synergistic growth inhibition with cisplatin in HeLa cells. - PubMed - NCBI (Dichloroacetate did not work, according to Ted),
ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection
Also this study is relevant which shows a possible con of acetate, in mice:
Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth*
Abstract
Tumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.
Source: Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth
And this one on sodium acetate alkalizing urine in salicylate toxicity which could shed some light on its effects on pH:
Sodium Acetate as an Alkalinizing Agent for Salicylate Intoxication: A Case Report
Abstract
Background: Urine and serum alkalization with sodium bicarbonate (NaHCO3) is the initial treatment for salicylate toxicity. Due to medication shortages, sufficient quantities of NaHCO3 may not be available and alternative treatments may be needed.
Case Report: This is an observational case report of a man who presented with chronic, inadvertent aspirin intoxication. Initially, we used a NaHCO3 continuous intravenous (IV) infusion until the hospital ran out of NaHCO3. Thereafter, the NaHCO3 IV infusion was replaced with a sodium acetate (SA) continuous IV infusion.
“Why should an emergency physician be aware of this?” Sodium acetate’s role in serum and urine alkalization for drug intoxications is not well understood. Physiologically, SA is converted to acetyl-coA and processed through the Krebs cycle, producing CO2 and later bicarbonate via carbonic anhydrase. In severe salicylism, key enzymes of the Krebs cycle are inhibited, ultimately forming lactate and preventing the conversion of SA to bicarbonate. We hypothesize that in our patient, the Krebs cycle continued to function as evidenced by the normal lactate level, suggesting a mild to moderate degree of chronic salicylate toxicity. At such levels, SA appears to be an effective means of serum and urine alkalization.
Source: Sodium Acetate as an Alkalinizing Agent for Salicylate Intoxication: A Case Report
Former RP forum user @natedawggh has listed sodium acetate in his "How I beat cancer list" on his website, The Blog. A citation from the source by him:
But the use of sodium acetate can help combat lactic acid excess. Sodium acetate is also a part of my approach to SIBO and metabolic disease (and the recipe is in that chapter too). By helping to reduce lactic acid it can help remove conditions which promote cancer growth. But acetic acid also promotes the formation of steroids and the healthy formation of cholesterol, among many other benefits which can help in cancer recovery.
Source: Cancer
Also interesting study: Electro-activation of potassium acetate, potassium citrate and calcium lactate: impact on solution acidity, Redox potential, vibrational properties of Raman spectra and antibacterial activity on E. coli O157:H7 at ambient temperature.
I drank it and I noticed it tasted alkaline, with only a scent of ACV I could smell while in my mouth, not actually taste. I normally really like the soury taste of ACV in water, so this was something different. After taking it, I noticed pain relief in my right shoulder and lung, where I've always had a cough and pain for 2 years now. Also internal congestion inside the lung felt like it was dissolving, and things were going down there I felt. I also felt a bit more energetic, and a bit more clarity. Breathing also feels more pleasant, and this stiffness of my right shoulder also seems to dissapear somewhat. All in all this first glass was a success and I plan on doing it more. I think I put in a bit too much baking soda, I will try a bit fewer the next time.
I actually wonder, what is the significance of the pH of the solution we're making, is there actually any? You might as well just buy potassium acetate and sodium acetate, put it in water and drink it up. Unreacted bicarbonate I might add, does aid the kidneys (the kidneys naturally produce their own bicarbonate), and if it produces CO2 in the body that's also a benefit. But drinking only ACV will give you potassium acetate as well so I wonder why Ted put baking soda with it, or I've might missed an explanation. If so, please excuse me! Also the alkaline pH could aid pathogens, so unless there's a specific reason for it, I think trying just potassium acetate powder and maybe sodium acetate powder could be worth it too for specific diseases, like cancer perhaps. Ted did mention that acidic substances like for example ascorbic acid, caused voltage of cells to become unhealthier and cause cancer though so that could be the reason! The common occurrence of both baking soda and apple cider vinegar in households and in local supermarkets/general stores is however quite a convenience, for its quick, cheap and easy access to make a ACV/BS solution.
I really like what this is doing to my body, and I do recommend it! Will be using it again, and report back.
Wouldn't these acetobacter species just add to the endotoxin burden of the gut? (From a Peat perspective) Curious.Perhaps it would be better to mix apple cider vinegar with potassium carbonate, thus yielding potassium acetate . . .
I like apple cider vinegar not so much for the acetate, but because it has Acetobacter species of bacteria. These bacteria are a good probiotic; since Acetobacter aceti has an alcohol dehydrogenase enzyme it can detoxify the ethanol, tyrosol, and tryptophol produced by Candida albicans. These bacteria also have membrane polysaccharides that stimulate the neutrophils and natural killer cells needed for destroy pathogens, and of course they also inhibit pathogenic bacteria & yeast simply through competition.
But something can also be said about the acetate present, and when mixed with the laurate found in shredded coconut or goat cheese it should produce an effective Candidacidal salad—even without the green onions, shallots, garlic, etc.
I am also wondering how the voltage of the cancer cell theory and its dynamics fits in with Ray Peat's recommendation of 1500-2000 mg of dietary calcium daily, and what calcium acetate could mean for health. Ray Peat recommends eggshell calcium, and it's popular among people to make calcium acetate by reacting the eggshell calcium with apple cider vinegar.
I also happened to come across these six significant studies:
Effect of sodium acetate on cell proliferation and induction of proinflammatory cytokines: a preliminary evaluation.
Food Chem Toxicol. 2005 Dec;43(12):1773-80.
Sun J1, Bi L, Chi Y, Aoki K, Misumi J.
Inner Mongolia Medical College, Huhehaote City, Inner Mongolia, China. [email protected]
Abstract
We have studied the effect of sodium acetate exposure on the viability and proliferative activity of cultured human gastric adenocarcinoma epithelial (AGS) cells and changes in the release of proinflammatory cytokines. We evaluated the levels of IL-6, TNF-alpha, IL-8, and IL-1beta in cell culture supernatants using enzyme-linked immunosorbent assays, and cytokine mRNA levels were measured in whole cells using reverse transcriptase-polymerase chain reaction. We also measured cytokine levels in mice using immunohistochemistry. In vitro studies demonstrated that incubation with sodium acetate (up to 12.5 mM) for 72 h stimulated AGS cell viability and proliferation in a dose-dependent manner; however, incubation with >12.5 mM sodium acetate inhibited cell growth, also in a dose-dependent manner (the largest decrease in viability was >50%). Incubation with sodium acetate for 24 h increased the levels of IL-1beta, IL-8, and TNF-alpha protein and mRNAs (IL-6 was detected but its mRNA was not). The effect of sodium acetate on the expression of these cytokines in cell culture was verified in mice. Our data suggest that ingestion of high concentrations of sodium acetate in food has cytotoxic effects.
Source: Effect of sodium acetate on cell proliferation and induction of proinflammatory cytokines: a preliminary evaluation. - PubMed - NCBI
Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release
Published: 21 February 2013
Cell Death & Disease volume 4, page e507 (2013)
C Marques, C S F Oliveira, S Alves, S R Chaves, O P Coutinho, M Côrte-Real & A Preto
Abstract
Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortality. Short-chain fatty acids secreted by dietary propionibacteria from the intestine, such as acetate, induce apoptosis in CRC cells and may therefore be relevant in CRC prevention and therapy. We previously reported that acetic acid-induced apoptosis in Saccharomyces cerevisiae cells involves partial vacuole permeabilization and release of Pep4p, the yeast cathepsin D (CatD), which has a protective role in this process. In cancer cells, lysosomes have emerged as key players in apoptosis through selective lysosomal membrane permeabilization (LMP) and release of cathepsins. However, the role of CatD in CRC survival is controversial and has not been assessed in response to acetate. We aimed to ascertain whether LMP and CatD are involved in acetate-induced apoptosis in CRC cells. We showed that acetate per se inhibits proliferation and induces apoptosis. More importantly, we uncovered that acetate triggers LMP and CatD release to the cytosol. Pepstatin A (a CatD inhibitor) but not E64d (a cathepsin B and L inhibitor) increased acetate-induced apoptosis of CRC cells, suggesting that CatD has a protective role in this process. Our data indicate that acetate induces LMP and subsequent release of CatD in CRC cells undergoing apoptosis, and suggest exploiting novel strategies using acetate as a prevention/therapeutic agent in CRC, through simultaneous treatment with CatD inhibitors.
Source: https://www.nature.com/articles/cddis201329
Apoptotic effect of sodium acetate on a human gastric adenocarcinoma epithelial cell line
Genet. Mol. Res. 15 (4): gmr.15048375 Published October 5, 2016
DOI http://dx.doi.org/10.4238/gmr.15048375
Y. Xia1 *, X.L. Zhang2 *, F. Jin3 *, Q.X. Wang1 , R. Xiao1 , Z.H. Hao4 , Q.D. Gui5 and J. Sun1
1 Inner Mongolia Medical University, Hohhot, China 2 Capital Medical University, Beijing, China 3 Inner Mongolia Vocational College of Chemical Engineering, Hohhot, China 4 Inner Mongolia People’s Hospital, Hohhot, China 5 International Mongolia Hospital of Inner Mongolia, China
ABSTRACT
The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.
Source: http://www.funpecrp.com.br/gmr/year2016/vol15-4/pdf/gmr8375.pdf
Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Published: November 20, 2013 Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Patrick M. Long, Scott W. Tighe, Heather E. Driscoll, John R. Moffett, Aryan M. A. Namboodiri, Mariano S. Viapiano, Sean E. Lawler, Diane M. Jaworski
Research article - Peer-reviewed
Abstract
Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation.
Source: Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells
Triacetin‐based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma
Cancer Cell Biology
First published: 30 August 2013 https://doi.org/10.1002/ijc.28465
Andrew R. Tsen Patrick M. Long Heather E. Driscoll Matthew T. Davies Benjamin A. Teasdale Paul L. Penar William W. Pendlebury Jeffrey L. Spees Sean E. Lawler Mariano S. Viapiano Diane M. Jaworski
Abstract
Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N‐acetyl‐l‐aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth‐inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor‐derived glioma stem‐like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli‐Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA‐induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA‐mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors.
Source: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.28465
Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules
British Journal of Cancer (2001) 84(6), 802–807 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1648
M Vasse1, D Thibout2, J Paysant1, E Legrand1, C Soria1,3 and M Crépin2
1Laboratoire DIFEMA, Groupe de Recherche MERCI, Faculté de Médecine et Pharmacie de Rouen, 22 Bd Gambetta, 76183 Rouen Cedex, France; 2UPRES 2360, équipe d’Oncologie Cellulaire et Moléculaire, SMBH Université de Paris 13, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France; 3U353, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Summary
Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDAMB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDAMB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1. © 2001 Cancer Research Campaign http://www.bjcancer.com
Source: http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2363819&blobtype=pdf
Also several interesting, related studies: ATP citrate lyase inhibition can suppress tumor cell growth, ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation,
An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis,
Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments. - PubMed - NCBI, ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch, Dichloroacetate shifts the metabolism from glycolysis to glucose oxidation and exhibits synergistic growth inhibition with cisplatin in HeLa cells. - PubMed - NCBI (Dichloroacetate did not work, according to Ted),
ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection
Also this study is relevant which shows a possible con of acetate, in mice:
Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth*
Abstract
Tumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.
Source: Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth
And this one on sodium acetate alkalizing urine in salicylate toxicity which could shed some light on its effects on pH:
Sodium Acetate as an Alkalinizing Agent for Salicylate Intoxication: A Case Report
Abstract
Background: Urine and serum alkalization with sodium bicarbonate (NaHCO3) is the initial treatment for salicylate toxicity. Due to medication shortages, sufficient quantities of NaHCO3 may not be available and alternative treatments may be needed.
Case Report: This is an observational case report of a man who presented with chronic, inadvertent aspirin intoxication. Initially, we used a NaHCO3 continuous intravenous (IV) infusion until the hospital ran out of NaHCO3. Thereafter, the NaHCO3 IV infusion was replaced with a sodium acetate (SA) continuous IV infusion.
“Why should an emergency physician be aware of this?” Sodium acetate’s role in serum and urine alkalization for drug intoxications is not well understood. Physiologically, SA is converted to acetyl-coA and processed through the Krebs cycle, producing CO2 and later bicarbonate via carbonic anhydrase. In severe salicylism, key enzymes of the Krebs cycle are inhibited, ultimately forming lactate and preventing the conversion of SA to bicarbonate. We hypothesize that in our patient, the Krebs cycle continued to function as evidenced by the normal lactate level, suggesting a mild to moderate degree of chronic salicylate toxicity. At such levels, SA appears to be an effective means of serum and urine alkalization.
Source: Sodium Acetate as an Alkalinizing Agent for Salicylate Intoxication: A Case Report
Former RP forum user @natedawggh has listed sodium acetate in his "How I beat cancer list" on his website, The Blog. A citation from the source by him:
But the use of sodium acetate can help combat lactic acid excess. Sodium acetate is also a part of my approach to SIBO and metabolic disease (and the recipe is in that chapter too). By helping to reduce lactic acid it can help remove conditions which promote cancer growth. But acetic acid also promotes the formation of steroids and the healthy formation of cholesterol, among many other benefits which can help in cancer recovery.
Source: Cancer
Also interesting study: Electro-activation of potassium acetate, potassium citrate and calcium lactate: impact on solution acidity, Redox potential, vibrational properties of Raman spectra and antibacterial activity on E. coli O157:H7 at ambient temperature.
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