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Nathan Goodyear

British Journal of Cancer - Dichloroacetate inhibits aerobic glycolysis in multiple mye... - 0 views

www.nature.com/...bjc2013120a.html

DCA dichloroacetate cancer

shared by Nathan Goodyear on 19 Nov 14 - No Cached
  • Nathan Goodyear on 19 Nov 14
     
    Dichloroacetate (DCA) inhibits aerobic glycolysis via inhibition of Pyruvate Dehydrogenase kinase (PDK), which allows for the phosphorylation of Pyruvate Dehydrogenase and the formation of acetylCo-A.  This then feeds the krebs cycle.  Increased mitochondrial activity increases ROS and resultant apoptosis of cancer cells.
Nathan Goodyear

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC2567082

cancer dichloroacetate dichloracetic acid DCA

shared by Nathan Goodyear on 07 Nov 18 - No Cached
  • The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis
  • The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour.
  • Because GO is far more efficient in generating ATP compared with GLY (producing 36 vs 2 ATP per glucose
  • ...9 more annotations...
  • molecule), cancer cells upregulate glucose receptors and significantly increase glucose uptake in an attempt to ‘catch up
  • early carcinogenesis often occurs in a hypoxic microenvironment, the transformed cells have to rely on anaerobic GLY for energy production.
  • Hypoxia-inducible factor (HIF) is activated in hypoxic conditions
  • evidence suggests that transformation to a glycolytic phenotype offers resistance to apoptosis
  • non-small cell lung cancer, breast cancer and glioblastoma
  • Dichloroacetate activated the pyruvate dehydrogenase, which resulted in increased delivery of pyruvate into the mitochondria
  • DCA increased GO and depolarised the mitochondria, returning the membrane potential towards the levels of the non-cancer cells, without affecting the mitochondria of non-cancerous cells
  • induction of apoptosis by DCA in non-small cell lung cancer, breast cancer and glioblastoma cell lines
  • DCA was shown to induce apoptosis in endometrial (Wong et al, 2008) and prostate (Cao et al, 2008) cancer cells
  • Nathan Goodyear on 07 Nov 18
     
    DCA as targeted therapy in cancer.
Nathan Goodyear

Dichloroacetate induces apoptosis in endometrial cancer cells - 0 views

Dichloroacetate induces apoptosis in endometrial cancer cells

DCA dichloracetic acid dichloroacetate cancer

shared by Nathan Goodyear on 07 Nov 18 - No Cached
  • Nathan Goodyear on 07 Nov 18
     
    DCA induces apoptosis of endometrial cancer cells in cell line study. DCA is a pyruvate dehydrogenase kinase inhibitor which will increase apoptosis and decrease proliferation. DCA serves to recapture the mitochondrial kreb's cycle and ETC coupling potential.
Nathan Goodyear

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and in... - 0 views

pubmed.ncbi.nlm.nih.gov/23420584

tumor microenvironment TME immunosuppression cancer immunomodulation DCA lactic acid

shared by Nathan Goodyear on 13 Mar 21 - No Cached
  • Nathan Goodyear on 13 Mar 21
     
    The title tells all: Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity
Nathan Goodyear

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views

www.ncbi.nlm.nih.gov/...PMC3601023

cancer DCA

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • the oral bioavailability of DCA is nearly 100%
  • the oral bioavailability of DCA is almost 100%.
  • DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
  • ...23 more annotations...
  • Clinical studies of DCA have shown reduced lactate levels
  • It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
  • The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
  • It is well known that many chemotherapeutic agents have a low therapeutic index in brain tumors.
  • The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
  • Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
  • In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
  • the level of Hsp70 was significantly decreased
  • DCA can penetrate the BBB
  • It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
  • Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
  • HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
  • Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
  • In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
  • DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
  • Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
  • The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
  • Under hypoxic conditions, hypoxia-inducible factor (HIF-1α) is activated and induces angiogenesis
  • In addition, HIF-1α can also induce the expression of PDK,48 which can inhibit the activity of PDH
  • The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
  • the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
  • In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
  • DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
  • Nathan Goodyear on 12 Nov 14
     
    DCA as proposed therapy in cancer.
Nathan Goodyear

Bicarbonate and dichloroacetate: Evaluating pH altering therapies in a mouse model for ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3125283

DCA dichloracetic acid dichloroacetate cancer "pH and cancer" acid alkaline

shared by Nathan Goodyear on 16 Nov 18 - No Cached
  • Nathan Goodyear on 16 Nov 18
     
    Tumor Microenvironment is hypoxia and acid which negates effects of therapies such as DCA. Alkalinization of the tumor micronenvironment is a means to open the tumor to the effects of therapies such as DCA.
Nathan Goodyear

Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate canc... - 0 views

www.ncbi.nlm.nih.gov/...18465755

DCA dichloroacetate dichloracetic acid cancer "prostate cancer"

shared by Nathan Goodyear on 07 Nov 18 - No Cached
  • Nathan Goodyear on 07 Nov 18
     
    DCA inhibits bcl to promote apoptosis and inhabit prostate cancer cell growth.
Nathan Goodyear

Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy - 1 views

www.ncbi.nlm.nih.gov/...PMC5067498

DCA dichloroacetate dichloracetic acid cancer colon cancer

shared by Nathan Goodyear on 18 Jan 18 - No Cached
  • inhibition of mitochondrial pyruvate dehydrogenase kinase
  • inhibition of aerobic glycolysis (the Warburg effect) and activation of mitochondrial potassium ion channels
  • angiogenesis blockade
  • ...5 more annotations...
  • changes in expression of HIF1-α
  • alteration of pH regulators V-ATPase and MCT1, and other cell survival regulators such as PUMA, GLUT1, Bcl2 and p53
  • DCA as a cancer stabilizing agent
  • A protocol of natural medications was developed to address the dose-limiting neurologic toxicity, in collaboration with a naturopathic physician (Andrews). The oral DCA regimen that was developed included three natural medications acetyl L-carnitine[29-31], R-alpha lipoic acid[32-34] and benfotiamine[35-37], for the primary purpose of neuropathy prevention
  • measurable benefits from DCA therapy in 60%-70% of cases
  • Nathan Goodyear on 18 Jan 18
     
    Good review of dichloracetate or DCA in antitumor activity.  DCA has been shown to have numerous anticancer properties.
Nathan Goodyear

Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells | Br... - 0 views

www.nature.com/6605701

DCA dichloroacetate dichloracetic acid cancer colorectal cancer

shared by Nathan Goodyear on 08 Nov 18 - No Cached
  • Nathan Goodyear on 08 Nov 18
     
    DCA induces apoptosis in colorectal cancer
Nathan Goodyear

Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC ... - 0 views

onlinelibrary.wiley.com/...ijc.25499

DCA dichloroacetate dichloracetic acid chemotherapy cancer

shared by Nathan Goodyear on 08 Nov 18 - No Cached
  • Nathan Goodyear on 08 Nov 18
     
    DCA works in synergy, augments, effects of anti-mitochondrial chemo agents cisplatin and topetecan
Nathan Goodyear

Non-Hodgkin's Lymphoma Reversal with Dichloroacetate - 0 views

www.hindawi.com/...414726

cancer NHL non-Hodgkin's Lymphoma Dichloroacetate DCA

shared by Nathan Goodyear on 31 May 19 - No Cached
  • Nathan Goodyear on 31 May 19
     
    Oral DCA leads to remission in NHL case study. The oral dose was 900 mg daily.
Nathan Goodyear

Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells via dow... - 0 views

www.ncbi.nlm.nih.gov/...PMC5312350

DCA Dichloroacetate breast cancer tamoxifen

shared by Nathan Goodyear on 17 Jul 19 - No Cached
  • Nathan Goodyear on 17 Jul 19
     
    DCA increased breast cancer cell sensitivity to tamoxifen
Nathan Goodyear

PO-238 Dichloroacetate (DCA) treatment affects mitochondrial activity and ste... - 0 views

esmoopen.bmj.com/...A113.1

cancer" DCA CSC pancreatic cancer stem cells cancer dichloracetic acid dichloroacetate

shared by Nathan Goodyear on 27 Nov 18 - No Cached
  • Nathan Goodyear on 27 Nov 18
     
    DCA shown to decrease tumor size in mouse model of pancreatic cancer stem cells.
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