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| Dichloroacetate (DCA) is a metabolic modulator that targets the altered metabolic state of cancer cells by inhibiting PDKs. This action impacts several key pathways: • Reversal of the Warburg effect • Restoration of mitochondrial function and promotion of apoptosis • suppresses glycolysis and promotes oxidative phosphorylation, thereby increasing mitochondrial ROS-mediated apoptosis in tumor cells • Increase in ROS production leading to oxidative stress • Inhibition of cell cycle progression • Modulation of HIF-1α signaling: DCA might decrease HIF-1α stabilization, thereby reducing the expression of genes that support glycolysis, angiogenesis, and survival under low-oxygen conditions. -DCA has been primarily used in treating congenital lactic acidosis—a rare genetic disorder characterized by the buildup of lactic acid in the body. -DCA is an anti-diabetic and lipid-lowering drug, as well as treating myocardial and cerebrovascular ischemia. -Do not add DCA to hot or warm beverages. DCA is unstable at higher temperatures -Caffeinated increases effectiveness -Vitamin B1 reduces neuropathy (500mg-2500mg/day) -Possibly 20 grams of citric acid 20 minutes before taking DCA -Procaine, Diclofenac or Sulindac to increase SMCT1 -Omeprazole 80mg/day to increase DCA effectiveness -Scorpion venom to increase DCA effectiveness -Metformin 1000mg to 1500mg/day -Propranolol (Ref.) -Fenbendazole shows strong synergy when combined to DCA, So it may make very much sense to combine the two. "Note: DCA is not tumor cell specific,> and therefore the same shift in glucose metabolism that occurs in cancer cells will also take place in immune cells, leading to induction of Tregs (Ref.). In order to avoid this possibility, while using DCA I would also use Treg inhibitors such as Cimetidine (Ref.) or low dose Cyclophosphamide (Ref.)." Dose: 10mg/kg/day and increase slowly to about 25mg/kg/day:(1/2morn,1/2evening) take 5 days on, 2 off? OR 2wks on/ 1wk off: https://www.thedcasite.com/dca_dosage.html Done by mixing it in water and drinking, suggested that DCA not be taken on an empty stomach. **** DCA-induced apoptosis in cancer cells requires sodium-coupled monocarboxylates transporter SLC5A8 (SMCT1) -Inhibitors of DNA methylation induce reactivation of SLC5A8 -Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. -SMCT1 was found to be stimulated by some other NSAIDs (diclofenac, meclofenamate and sulindac), by activin A143 and by the probiotic Lactobacillus plantarum. SMCT1 has been found to be inhibited by some NSAIDs (ibuprofen, ketoprofen, fenoprofen, naproxen135 and indomethacin94), phytochemicals (resveratrol and quercetin) **** Hence these should be avoided with DCA. (also AVOID Bromide, iodide and sulfite ) **** GSTZ1 an/or chloride anion transport inhibitors also reduce resistance to DCA (if the tumor expresses GSTZ1 and contains a high chloride anions level, the GSTZ1 will be stable, maintaining the resistance to DCA). -Dichloroacetate-dca-treatment-strategy GSTZ1 an/or chloride anion transport inhibitors. . -Etacrynic acid is a Cl(-)-ATPase inhibitor -Lansoprazole and Omeprazole inhibit chloride channels. -Chlorotoxin found in scorpion venom (see my post on scorpion venom) can also inhibit chlorine channels Sources: https://northernhealthproducts.com/shop/ https://www.dcalab.com/
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| – PDK1 is often upregulated in cancers and is central to the metabolic reprogramming (Warburg effect) that allows tumor cells to favor glycolysis over oxidative phosphorylation. – Elevated PDK1 expression has been correlated with aggressive tumor behavior and poor prognosis in several cancer types, including non‐small cell lung cancer, ovarian cancer, and gastric cancer. – Although PDK2 has a similar catalytic role as PDK1, its expression levels and impact may vary. – Some studies have observed that increased PDK2 expression is associated with more aggressive cancer features and resistance to therapy in certain tumor types. – PDK3 is often upregulated in response to hypoxic conditions—a common feature of solid tumors—which can further drive metabolic divergence in cancer cells. – The role of PDK4 appears to be more variable. In some settings, its activity might be lower in tumor cells to favor the use of glycolysis, while in others, it may be upregulated as part of broader metabolic adaptations. -By upregulating PDKs, cancer cells limit the flux of pyruvate into the mitochondria, thereby promoting glycolysis. |
| 5194- | DCA, | Metabolic modulation of glioblastoma with dichloroacetate |
| - | vitro+vivo, | GBM, | NA |
| 4901- | DCA, | Sal, | Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer |
| - | Review, | NSCLC, | NA |
| 1889- | DCA, | A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth |
| - | Review, | Var, | NA |
| 1887- | DCA, | GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate |
| - | in-vitro, | Var, | NA |
| 1885- | DCA, | Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | CRC, | SW-620 | - | in-vitro, | CRC, | HT-29 |
| 1884- | DCA, | Sal, | Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines |
| - | in-vitro, | CRC, | DLD1 | - | in-vitro, | CRC, | HCT116 |
| 1882- | DCA, | Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer |
| - | Analysis, | NA, | NA |
| 1878- | DCA, | 5-FU, | Synergistic Antitumor Effect of Dichloroacetate in Combination with 5-Fluorouracil in Colorectal Cancer |
| - | in-vitro, | CRC, | LS174T | - | in-vitro, | CRC, | LoVo | - | in-vitro, | CRC, | SW-620 | - | in-vitro, | CRC, | HT-29 |
| 1877- | DCA, | Non-Hodgkin′s Lymphoma Reversal with Dichloroacetate |
| - | Case Report, | lymphoma, | NA |
| 1875- | DCA, | Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells |
| - | in-vitro, | neuroblastoma, | NA | - | in-vivo, | NA, | NA |
| 1873- | DCA, | Dual-targeting of aberrant glucose metabolism in glioblastoma |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | U251 |
| 1872- | DCA, | Dichloroacetate, a selective mitochondria-targeting drug for oral squamous cell carcinoma: a metabolic perspective of treatment |
| - | in-vitro, | Oral, | HSC2 | - | in-vitro, | Oral, | HSC3 |
| 1864- | DCA, | MET, | Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | T47D | - | in-vitro, | Nor, | MCF10 |
| 1867- | DCA, | Chemo, | Sensitization of breast cancer cells to paclitaxel by dichloroacetate through inhibiting autophagy |
| - | in-vivo, | BC, | NA | - | in-vitro, | BC, | NA |
| 2044- | PB, | DCA, | Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate |
| - | in-vivo, | NA, | NA |
| 1888- | VitB1/Thiamine, | DCA, | High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate |
| - | in-vitro, | PC, | SK-N-BE | - | NA, | PC, | PANC1 |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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