DCA, Dichloroacetate: Click to Expand ⟱
Features:
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/


Scientific Papers found: Click to Expand⟱
1865- DCA,    Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo
- in-vivo, BC, NA - in-vitro, BC, MCF-7 - in-vitro, BC, T47D
TumCG↓, growth of several breast cancer cell lines (MCF-7, T47D, 13762 MAT and V14 cells) was found to be inhibited by DCA in vitro.
TumCP↓, inhibition of proliferation
AntiCan↑, demonstrate the anti-cancer potential of DCA and the reversing the glycolytic phenotype.

1889- DCA,    A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth
- Review, Var, NA
PDKs↓, Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK)
Glycolysis↓, shifts metabolism from glycolysis to glucose oxidation
mt-H2O2↑, increases mitochondrial H2O2
Apoptosis↑, DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity
TumCP↓,
TumCG↓,
toxicity∅,

1887- DCA,    GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate
- in-vitro, Var, NA
GSTZ1∅, high levels of GSTZ1 expression confers resistance to the effect of high concentrations of DCA on cell viability
eff↓, These results may have important clinical implications in determining intratumoral metabolism of DCA and, consequently, appropriate oral dosing.
PDKs↓, inhibitor of mitochondrial pyruvate dehydrogenase kinase (PDK), DCA maintains the pyruvate dehydrogenase complex (PDC) in its active, unphosphorylated state
Chl∅, [Cl-] in tumors is often abnormally high compared to the surrounding tissue
eff↓, changes in [Cl-] could have an impact on DCA treatment, because a tumor with high GSTZ1 expression and high [Cl-] could exhibit atypical resistance to the anti-tumor effects of the drug.

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
SMCT1∅, SLC5A8 transports dichloroacetate very effectively with high affinity. This transporter is expressed in normal cells, but the expression is silenced in tumor cells via epigenetic mechanisms.
eff↓, lack of the SLC5A8 transporter makes tumor cells resistant to the antitumor activity of dichloroacetate.
eff↑, However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells, and prostate cancer cells.
eff↑, our findings suggest that combining dichloroacetate with a DNA methylation inhibitor would offer a means to reduce the doses of dichloroacetate to avoid detrimental effects associated with high doses but without compromising antitumor activity.
PDKs↓, Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase (PDK), which phosphorylates the E1α subunit of PDC and inactivates the complex
MMP↓, depolarization of the mitochondrial membrane,
Glycolysis↓, suppression of glycolysis
mitResp↑, enhancement of mitochondrial oxidation
ROS↑, production of reactive oxygen species,
eff↑, In control cells, which did not express the transporter, dichloroacetate did not have any significant effect. However, under identical conditions, SLC5A8-expressing cells underwent apoptosis to a marked extent. This phenomenon was seen in all three c

1884- DCA,  Sal,    Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines
- in-vitro, CRC, DLD1 - in-vitro, CRC, HCT116
eff↑, The effect of combination of dichloracetate and salinomycin on multicellular spheroid size was stronger than the sum of both monotherapies, particularly in HCT116 cells
pH↓, and in contrast, it is not related to dichloroacetate-induced reduction of intracellular pH
PDKs↓, Dichloroacetate (DCA) is a small synthetic molecule that is known as a pyruvate dehydrogenase kinase inhibitor. Its anticancer properties involve reversing the Warburg effect by switching ATP production back to oxidative phosphorylation
Warburg↓,

1883- DCA,    In vivo metabolic response of glucose to dichloroacetate in humans
- Analysis, Var, NA
BG↓, Dichloroacetate (DCA), which is known to increase the rate of pyruvate oxidation, has been shown to lower plasma glucose concentrations in normal fasting subjects
glucoNG↓, These results suggest that DCA may decrease gluconeogenesis by limiting the availability of the precursor substrates lactate and alanine.

1882- DCA,    Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer
- Analysis, NA, NA
PDKs↓, DCA activates PDH by inhibition of PDK at concentration of 10–250 μM
PDH↑,
lactateProd↓, decrease in lactate levels in both the blood and the cerebrospinal fluid.
Half-Life∅, Although the initial half-life with the first dose is less than one hour, this half-life increases to several hours with subsequent doses.

1881- DCA,  Chemo,    Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report
- in-vitro, NA, HT1080 - in-vitro, NA, WI38 - Case Report, Var, NA
eff↑, DCA combined with OPZ and TAM exhibited more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells, but did not influence proliferation of WI-38 human fibroblasts.
selectivity↑,
OS↑, Disease progression was successfully blocked (the rise of serum CA19-9 value) for three months, also confirmed by CT.

1880- DCA,    A Novel Form of Dichloroacetate Therapy for Patients With Advanced Cancer: A Report of 3 Cases
- Case Report, Var, NA
OS↑, 3 cases with patients who had recurrent cancers and for whom all conventional therapies had failed
angioG↓, (1) inhibition of angiogenesis
Hif1a↝, (2) alteration of expression of hypoxia-inducible factor 1-α (HIF1-α)
pH↝, (3) alteration of pH regulators vacuolar-type H + -ATPase (V-ATPase) and monocarboxylate transporter 1 (MCT1)
QoL↑, DCA has the potential to extend life without reducing patients’ quality of life with debilitating side effects or compromising physiological function, even for disease in a very advanced stage

1879- DCA,    Long-term stabilization of metastatic melanoma with sodium dichloroacetate
- Case Report, Melanoma, NA
OS↑, DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of recurrent metastatic melanoma for over 4 years’ duration, with trivial side effects.
toxicity↓, DCA was noted to have an absence of renal, pulmonary, bone marrow and cardiac toxicity
Dose∅, Active hexose correlated compound or AHCC , dandelion root, curcumin, and astragalus root. Parenteral therapy was also started, which consisted of intravenous vitamin C twice weekly and subcutaneous European mistletoe extract. +vegan diet
Dose∅, DCA 500 mg 3 times per day, which was equivalent to 17 mg/kg per day (manufacturer: Tokyo Chemical Industry, United States) in addition to maintaining the other natural therapies. 2 wk on and 1 wk off
Dose∅, To minimize the occurrence of DCA side effects, 3 additional natural medications were prescribed: Oral acetyl L-carnitine 500 mg 3 times a day, oral benfotiamine 80 mg twice a day and oral R-alpha lipoic acid 150 mg 3 times a day
QoL∅, DCA therapy can be used without reducing quality of life

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
tumCV↓, DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU
eff↑, synergistic antiproliferation in combination with 5-FU
PDKs↓, Dichloroacetate (DCA) is a prototypical inhibitor of mitochondrial PDK
lactateProd↓, DCA decreases lactate production by shifting the metabolism of pyruvate from glycolysis towards oxidation in the mitochondria
Glycolysis↓,
mitResp↑, DCA restored mitochondrial function
TumCCA↑, DCA potentiated the cell cycle arrest in G1 phase.
Bcl-2↓, DCA and 5-FU decreased Bcl-2 expression significantly as compared with DCA or 5-FU alone
BAX↑, Bax and caspase-3 were significantly increased in the four CRC cell lines treated with combination of DCA and 5-FU compared to their single usage
Casp3↑,

1877- DCA,    Non-Hodgkin′s Lymphoma Reversal with Dichloroacetate
- Case Report, lymphoma, NA
Remission↑, Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later.
p‑PDKs↓, DCA has been shown to block this phosphorylation by PDK at the mitochondrial membrane level and decrease glycolysis in favor of glucose oxidation
Glycolysis↓,
i-Ca+2↓, This return to a normal metabolism of glucose allows for major changes including a decrease in Ca++ intracellularly, and stabilization of the mitochondria allowing a reactivation of caspases in cancer cells leading to apoptosis
toxicity↓, A reversible, minimal nerve damage can be considerably reduced by a daily thiamine intake of several hundred milligrams for humans. thiamine amount varies from 50 mg/day to 100 mg/day depending on whether it is administered orally or injected
Dose∅, A Non-Hodgkin′s lymphoma patient taking 10 mg/kg [750 mg] of dichloroacetate daily of his own accord, had a complete remission of his Non-Hodgkin′s lymphoma cancer after four months

1876- DCA,  Chemo,    In vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines
- in-vivo, Lung, H727
eff↑, DCA (10 mM) inhibited the growth of UMC- 11 cells by 22% and sensitised these highly resistant cells to carboplatin, satraplatin and JM118 1.4-2.4-fold.
TumCG↓,
Glycolysis↓, DCA that promotes mitochondrial respiration over aerobic glycolysis
mitResp↑,

1875- DCA,    Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells
- in-vitro, neuroblastoma, NA - in-vivo, NA, NA
selectivity↑, acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells.
AntiCan↑, DCA exhibits an unexpected anticancer effect on NB tumor cells
TumVol↓, growth inhibition became statistically significant when mice were treated with 25 mg/kg/dose of DCA (55% of reduction compared with control group)
PDKs↓, effects of DCA are related to PDK inhibition, mitochondrial oxidative phosphorylation activation and specific mitochondrial hyperpolarization reduction,
mt-OXPHOS↑,
MMP↓,
Glycolysis↓, shifting cellular metabolism from glycolysis to glucose oxidation, without any deleterious effect on normal cells.
toxicity↓, Indeed, more than 40 clinical trials of DCA report that the most significant adverse effect of long-term DCA administration is a reversible peripherical neuropathy.
Warburg↓, indeed, DCA is able to reverse the Warburg effect by inhibiting PDK, restoring mitochondrial membrane potential and increasing ROS production.
ROS↑,
eff↑, DCA was celebrated as the magic bullet against cancer, even if it is currently not yet approved for cancer treatment.

1874- DCA,    Dichloroacetate induces apoptosis of epithelial ovarian cancer cells through a mechanism involving modulation of oxidative stress
- in-vitro, Ovarian, SKOV3 - in-vitro, Ovarian, MDAH-2774
Apoptosis↑, Dichloroacetate induced apoptosis, reduced MPO, iNOS, and HIF-1a,
MPO↓,
iNOS↓, 40 and 80 mg/mL DCA doses,
Hif1a↓,
SOD↑, increased SOD
Casp3↑, Treatment with DCA significantly ncreased caspase 3 activity in SKOV-3 cells, in a dose-dependent manner, from 6.53 to 12.2, 16.9, and 22.1 mmol/L in the 20, 40, and 80 mg/mL doses, respectively

1873- DCA,    Dual-targeting of aberrant glucose metabolism in glioblastoma
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
PDKs↓, dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor.
eff↑, By combining DCA with PENAO, the two drugs worked synergistically to inhibit cell proliferation (but had no significant effect on non-cancerous cells)
selectivity↑,
MMP↓, induced oxidative stress and depolarized mitochondrial membrane potential, which in turn activated mitochondria-mediated apoptosis
ROS↑,
Apoptosis↑,
Warburg↓, Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor that reverses the Warburg effect
eff↑, DCA has been demonstrated to sensitize cancer cells towards apoptosis and enhance the effects of several anti-cancer agents, including arsenic trioxide [20], cisplatin [22,23] and metformin [24].
Dose∅, IC50 values of DCA were at suprapharmacological millimolar level
toxicity∅, whilst the IC50 values of DCA for non-cancerous cells were not reached (DCA concentration in this study was tested up to 50 mM)

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
PDKs↓, Dichloroacetate (DCA) is a specific inhibitor of the PDH-regulator PDK proved to foster mitochondrial oxidation of pyruvate.
ROS↑, enhanced production of reactive oxygen species
OCR↑, DCA - a mildly cytotoxic concentration - caused, indeed, an increase of the resting endogenous OCR in all the three OSCC cell lines
other↑, Consequently, the OxPhos/Glycolysis flux ratio increased largely in HSC-2 and scantly in PE15 with an intermediate value for HSC-3

1870- DCA,  Rad,    Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation
- in-vitro, Pca, PC3
TumCCA↑, DCA alone produced significant cytotoxic effects and was associated with G1 cell cycle arrest.
Apoptosis↑, DCA was associated with an increased rate of apoptosis
MMP↓, DCA therapy resulted in a significant change in mitochondria membrane potential
eff↑, demonstrate DCA can effectively sensitize wild-type and over expressing Bcl-2 human prostate cancer cells to radiation by modulating the expression of key members of the Bcl-2 family.
RadioS↑,

1869- DCA,    Dichloroacetate induces autophagy in colorectal cancer cells and tumours
- in-vitro, CRC, HT-29 - in-vitro, CRC, HCT116 - in-vitro, Pca, PC3 - in-vitro, CRC, HT-29
LC3II↑, Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo
ROS↑, increased production of reactive oxygen species (ROS)
mTOR↓, mTOR inhibition
MCT1↓, DCA is a possible competitive MCT-1 inhibitor
NADH:NAD↓, increased NAD+/NADH ratios
NAD↑,
TumAuto↑, DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced kPL and increased NAD+/NADH ratio.
lactateProd↓, DCA treatment reduces lactate excretion with no change in glucose uptake
LDH↑, Increased LDH activity

1868- DCA,  MET,    Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
- Case Report, NA, NA
eff↑, DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity
toxicity∅,
MMP↓, In the initial 2007 paper by Bonnet et al[1], it was reported that DCA reduced mitochondrial membrane potential resulting in selective apoptosis in cancer cells.
Apoptosis↑,
selectivity↑,
pH↝, alteration of pH regulators V-ATPase and MCT1
Dose↝, The neuropathy risk with inclusion of natural neuroprotective agents was roughly 20% with 20-25 mg/kg per day dosing on a 2 wk on/1 wk off cycle.
Dose↝, 3 natural supplements were prescribed: Alpha lipoic acid (racemic) 500 mg i.v. with each DCA dose, oral R-alpha lipoic acid 150 mg 3 times a day, oral acetyl L-carnitine 500 mg 3 times a day, and oral benfotiamine 80 mg twice a day.
eff↑, Oral metformin was added to help sensitize the cancer to the chemotherapy, starting at 500 mg orally once a day with titration up to 500 mg 3 times a day

1867- DCA,  Chemo,    Sensitization of breast cancer cells to paclitaxel by dichloroacetate through inhibiting autophagy
- in-vivo, BC, NA - in-vitro, BC, NA
TumCG↓, Synergistic inhibition of tumor growth in mice treated with Dox and DCA.
eff↑, DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro.
OS↑, Moreover, the combined therapy of Dox and DCA could significantly inhibit tumor growth in vivo and prolong mouse survival time.
PDKs↓, Dichloroacetate (DCA) is a small inhibitor of pyruvate dehydrogenase kinase (PDK), which activates pyruvate dehydrogenase (PDH), and increases glucose oxidation by promoting influx of pyruvate into the Krebs cycle.
PDH↑,

1866- DCA,  MET,  BTZ,    Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner
- in-vivo, NA, NA
eff↑, Metformin, DCA, and oxamate effectively attenuated bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female mice.
TumCG↓,
Hif1a↓, Metformin, a widely used antidiabetic drug, has been shown to inhibit the expression of HIF1A
PDH↑, Dichloroacetate (DCA), a small molecule inhibitor, targets PDHK, thereby activating PDH and promoting the entry of pyruvate into the mitochondrial Krebs cycle
lactateProd↓, Oxamate, an analog of pyruvate, inhibits lactate dehydrogenase, thereby reducing the production of lactate and attenuating the pain-inducing effects of extracellular acidification (25) in mice with bortezomib-induced neuropathic pain (4
TumVol↓,
TumW↓,
Glycolysis↑, These findings suggest that targeting aerobic glycolysis with DCA or oxamate can complement the anticancer efficacy of bortezomib in male tumor-bearing mice.
neuroP↑, Metformin and aerobic glycolysis inhibitors attenuate bortezomib-induced neuropathic pain without compromising anticancer efficacy in female tumor-bearing mice

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
PDKs↓, Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism
eff↑, DCA and metformin are used in combination, synergistic induction of apoptosis of breast cancer cells occurs.
ROS↑, Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production.
PDK1↓,
lactateProd↓, also diminishes metformin promoted lactate production.
p‑PDH↑, DCA is an inhibitor of pyruvate dehydrogenase kinase (PDK) which phosphorylates pyruvate dehydrogenase (PDH), rendering it inactive
Dose∅, DCA (2.5 mM) and metformin (1 mM)
OCR↑, DCA treated cells had a significantly higher oxygen consumption rate compared to control cells.
DNA-PK↑,
γH2AX↑, phosphorylatoin of histone H2AX (p-H2AX), which is a useful surrogate marker of such DNA damage
cl‑PARP↑, large increase of cleaved PARP
selectivity↑, Importantly, we also show that this combination of drugs does not kill non-transformed breast epithelial cells MCF10A under the same conditions in which the drugs kill cancer cells.
*toxicity∅, does not kill non-transformed breast epithelial cells MCF10A under the same conditions in which the drugs kill cancer cells.

2044- PB,  DCA,    Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate
- in-vivo, NA, NA
PDK1↓, We investigated the inhibitory activity of phenylbutyrate toward PDKs and found that PDK isoforms 1-to-3 are inhibited whereas PDK4 is unaffected.
PDKs↓,
eff↑, phenylbutyrate combined to DCA results in greater increase of PDHC activity compared to each drug alone.
PDH↑,

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
p‑PDH↓, Both thiamine and DCA reduced the extent of PDH phosphorylation, reduced glucose consumption, lactate production, and mitochondrial membrane potential.
GlucoseCon↓, High dose thiamine reduces glucose consumption and lactate production
lactateProd↓,
MMP↓,
Casp3↑, High dose thiamine and DCA did not increase ROS but increased caspase-3 activity
eff↑, Our findings suggest that high dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate
PDKs↓,
selectivity↑, An advantage to targeting PDK activity is that overexpression of PDKs and extensive phosphorylation of PDH is found in cancer cells and not in normal tissue [14]. This may provide for selective targeting towards malignant tissue
TumCG↓, thiamine suppressed tumor growth at doses greater than 75 times the recommended daily intake
Dose∅, IC50 of thiamine was lower than DCA for both cell lines with values of 4.9 for SK-N-BE and 5.4 mM for Panc-1.
MMP↓, decrease in mitochondrial membrane potential
ROS∅, cells treated with thiamine or DCA were assayed for peroxide following 30 min, 1 h, and 2 h of treatment. No significant change in ROS was observed over all time
toxicity↑, Smithline et al. reported no adverse effects in healthy patients who were given 1.5g/day of thiamine [34]. Only minor side effects, such as nausea and indigestion were reported in patients given doses as high as 7.5 g/day
antiOx↑, Free thiamine has direct antioxidant properties


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

Results for Effect on Cancer/Diseased Cells:
angioG↓,1,   AntiCan↑,2,   antiOx↑,1,   Apoptosis↑,5,   BAX↑,1,   Bcl-2↓,1,   BG↓,1,   i-Ca+2↓,1,   Casp3↑,3,   Chl∅,1,   DNA-PK↑,1,   Dose↝,2,   Dose∅,7,   eff↓,3,   eff↑,18,   glucoNG↓,1,   GlucoseCon↓,1,   Glycolysis↓,6,   Glycolysis↑,1,   GSTZ1∅,1,   mt-H2O2↑,1,   Half-Life∅,1,   Hif1a↓,2,   Hif1a↝,1,   iNOS↓,1,   lactateProd↓,6,   LC3II↑,1,   LDH↑,1,   MCT1↓,1,   mitResp↑,3,   MMP↓,7,   MPO↓,1,   mTOR↓,1,   NAD↑,1,   NADH:NAD↓,1,   neuroP↑,1,   OCR↑,2,   OS↑,4,   other↑,1,   mt-OXPHOS↑,1,   cl‑PARP↑,1,   PDH↑,4,   p‑PDH↓,1,   p‑PDH↑,1,   PDK1↓,2,   PDKs↓,13,   p‑PDKs↓,1,   pH↓,1,   pH↝,2,   QoL↑,1,   QoL∅,1,   RadioS↑,1,   Remission↑,1,   ROS↑,6,   ROS∅,1,   selectivity↑,6,   SMCT1∅,1,   SOD↑,1,   toxicity↓,3,   toxicity↑,1,   toxicity∅,3,   TumAuto↑,1,   TumCCA↑,2,   TumCG↓,6,   TumCP↓,2,   tumCV↓,1,   TumVol↓,2,   TumW↓,1,   Warburg↓,3,   γH2AX↑,1,  
Total Targets: 70

Results for Effect on Normal Cells:
toxicity∅,1,  
Total Targets: 1

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:288  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page