PDK1 Cancer Research Results

PDK1, Pyruvate dehydrogenase kinase 1: Click to Expand ⟱

Source:

Type:

PDK1 (3-phosphoinositide-dependent protein kinase-1) (PDPK1) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell growth, survival, and metabolism. It is a key component of the PI3K/Akt signaling pathway, which is often dysregulated in cancer.
Overexpression or hyperactivation of PDK1 can lead to increased cell proliferation, survival, and resistance to apoptosis, contributing to tumorigenesis.
Inhibitors of PDK1 are being explored in preclinical and clinical studies as a means to disrupt cancer cell growth and survival.

Scientific Papers found: Click to Expand⟱

267-

ALA,

α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells

vitro+vivo,

Lung,

A549

 1.5 mM LA for 24 h

vitro+vivo,

Lung,

PC9

Apoptosis↑,
ROS↑, mitochondrial ROS(remarkably increased)
PDK1↓,
NRF2↓,
PDK1↓,
Bcl-2↓,
Casp9↑,
Dose∅, 1.5 mM LA for 24 h

999-

Ba,

Baicalin Inhibits EMT through PDK1/AKT Signaling in Human Nonsmall Cell Lung Cancer

in-vitro,

Lung,

H460

TumCP↓,
p‑PDK1↓,
p‑Akt↓,
EMT↓, baicalin effectively inhibited the EMT of NSCLC.
E-cadherin↑,
Vim↓,

2473-

BA,

Baicalin Inhibits EMT through PDK1/AKT Signaling in Human Nonsmall Cell Lung Cancer

in-vitro,

Lung,

A549

30uM

85.12 uM

in-vitro,

Nor,

BEAS-2B

140.7 μM

normal cells

in-vitro,

Lung,

H460

53.93 uM

EMT↓, Baicalin impedes EMT by inhibiting the PDK1/AKT pathway in human NSCLC and thus may be an effective alternative treatment for carcinoma and a new candidate antimetastasis drug.
PDK1↓, Baicalin Inhibited PDK1/AKT Signaling Pathway in NSCLC
Akt↓,
TumCMig↓, At 30 μM, this compound considerably inhibited migration and clone formation in NSCLC cell lines.
E-cadherin↑,
Vim↓, figure 3

2620-

Ba,

Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review

Review,

GC,

Hif1a↓, Baicalein reduces the levels of HIF-1α in AGS gastric cancer cells in a dose-dependent manner (10, 20, and 40 µM)
HK2↓, down-regulates the levels of HK2, LDHA, and PDK1
LDHA↓,
PDK1↓,
p‑Akt↓, inhibits Akt phosphorylation under hypoxic conditions
PTEN↑, promotes the expression of PTEN protein
GlucoseCon↓, gradually restores glucose uptake and lactic acid production in hypoxic AGS cells to those observed under normoxic conditions
lactateProd↓,
Glycolysis↓, Baicalein and other compounds could directly regulate glycolysis-related enzymes

2617-

Ba,

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

Review,

Var,

Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2616-

Ba,

The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products

Review,

Var,

Glycolysis↓, Related experiments have found that baicalein, the aglycone of baicalein inhibited hypoxia-enhanced glycolytic flux in AGS cells
HK2↓, and reduced the expression of key glycolytic-related enzymes such as HK2, lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1)
LDHA↓,
PDK1↓,
PTEN↑, Baicalein can also inhibit hypoxia-induced AKT phosphorylation by enhancing PTEN accumulation

2295-

Ba,

5-FU,

Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway

in-vitro,

GC,

AGS

ChemoSen↑, baicalein increased the sensitivity of AGS cells to 5-FU treatment under hypoxia
HK2↓, hypoxia-enhanced glycolytic flux and expression of several critical glycolysis-associated enzymes (HK2, LDH-A and PDK1) in the AGS cells were suppressed by baicalein
LDHA↓,
PDK1↓,
Akt↓, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-1α (HIF-1α) expression in AGS cells
PTEN↑,
Hif1a↓,
Glycolysis↓, results together suggest that inhibition of glycolysis via regulation of the PTEN/Akt/HIF-1α signaling pathway may be one of the mechanisms whereby baicalein reverses 5-FU resistance in cancer cells under hypoxia.
ROS↑, Taniguchi et al found that baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in cancer cells through DR5 upregulation mediated by ROS induction and CHOP/GADD153 activation
CHOP↑,

2298-

Ba,

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Review,

Var,

TumCG↓, Baicalein significantly reduced intracerebral tumor growth and proliferation and promoted apoptosis and cell cycle arrest in orthotopic U87 gliomas in mice
TumCP↓,
Hif1a↓, suppression of HIF-1α by baicalein contributed to its reduction of cell viability in ovarian cancer (OVCAR-3 and CP-70) cell lines. 20-μM and 40-μM.
VEGF↓, Suppression of HIF-1α/VEGF pathway
ChemoSen↑, Moreover, baicalein increased the sensitivity of gastric cancer cells (AGS) to 5-fluorouracil (5-FU) under hypoxic conditions
Glycolysis↓, baicalein suppressed the expression of glycolysis-associated enzymes including HKII, PDK1, and LDHA via inhibition of Akt-phosphorylation, which led to HIF-1α suppression
HK2↓,
PDK1↓,
LDHA↓,
p‑Akt↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells. (orginal paper)

2702-

BBR,

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1975

TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
MAPK↓,
FOXO3↑,
TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
TumCMig↓,
TumCI↓,
Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

2710-

BBR,

Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells

in-vitro,

Ovarian,

SKOV3

Warburg↓, berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly.
miR-145↑,
HK2↓, westernblot suggested that berberine could significantly down regulate the expression of HK2
TET3↑, Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene.
Glycolysis↓, Furthermore, the effect of berberine on glycolysis related enzymes was detected, the results of qRT-PCR and westernblot suggested that berberine could significantly down regulate the expression of HK2
PKM2↓, Western blot results showed down-expression of miR-145 reversed berberine's inhibition of HK2 expression. PKM2, pyruvate kinase M2; HK2, Hexokinase2; GLUT1, glucose transporter 1; LDH, lactate dehydrogenase; PFK2, phosphofructokinase 2; PDK1,
GLUT1↓,
LDH↓,
PFK2↓,
PDK1↓,

5586-

BetA,

Suppression of HIF-1α accumulation by betulinic acid through proteasome activation in hypoxic cervical cancer

in-vitro,

Cerv,

HeLa

Hif1a↓, We found that BA inhibited the hypoxia-induced accumulation of HIF-1α without affecting HIF-1α mRNA levels
VEGF↓, suppressed the expression of HIF target genes, including VEGF, GLUT1, and PDK1 in HeLa cells.
GLUT1↓,
PDK1↓,

2716-

BetA,

Cellular and molecular mechanisms underlying the potential of betulinic acid in cancer prevention and treatment

Review,

Var,

AntiCan↑, BA has a range of well-documented pharmacological and biological effects, including antibacterial, immunomodulatory, diuretic, antiviral, antiparasitic, antidiabetic, and anticancer activities
TumCD↑, anticancer properties of BA are mediated by the activation of cell death and cell cycle arrest, production of reactive oxygen species, increased mitochondrial permeability, modulation of nuclear factor-κB and Bcl-2 family signaling
TumCCA↑,
ROS↑,
NF-kB↓,
Bcl-2↓,
Half-Life↝, The half-life eliminations were 11.8 and 11.5 h after 500 and 250 mg/kg of intraperitoneal (i.p.) BA administration
GLUT1↓, the expression of HIF target genes, such as GLUT1, VEGF, and PDK1 was also suppressed by BA
VEGF↓,
PDK1↓,

2738-

BetA,

Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vivo,

NA,

mice

TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

943-

BetA,

Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway

in-vitro,

BC,

MCF7

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

mouse model

Glycolysis↓,
lactateProd↓,
GlucoseCon↓,
ECAR↓,
cMyc↓,
LDHA↓,
p‑PDK1↓,
PDK1↓,
Cav1↑, Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation
*Glycolysis↑, BA could lead to increased glycolysis in mouse embryonic fibroblasts by activating LKB1/AMPK pathway, whereas we found that BA inhibited aerobic glycolysis in breast cancer cells by modulating Cav-1/NF-ÎºB/c-Myc signaling
selectivity↑,
OCR↓, OCR parameters including the basal respiration, maximal respiration and spare respiratory capacity were also simultaneously inhibited
OXPHOS↓, implying that the activity of mitochondrial oxidative phosphorylation (OXPHOS) chain was also suppressed by BA

6547-

BSB,

Antitumor effects of a-bisabolol against pancreatic cancer

vitro+vivo,

PC,

PANC1

in-vitro,

PC,

MIA PaCa-2

in-vitro,

PC,

KLM1

in-vitro,

PC,

KP4

in-vitro,

Nor,

ACBRI515

TumCP↓, Bisabolol induced a decrease in cell proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1, MIA Paca2), but not in pancreatic epithelial cells (ACBRI515).
selectivity↑,
Apoptosis↑, α-Bisabolol treatment induced apoptosis and suppressed Akt activation in pancreatic cancer cell lines.
Akt↓,
EGR1↑, α-bisabolol treatment induced the overexpression of early growth response-1 (EGR1), whereas EGR1 siRNA decreased the α-bisabolol-induced cell death of KLM1 cells.
TumCG↓, Tumor growth in both subcutaneous and peritoneal xenograft nude mouse models was significantly inhibited by intragastric administration of 1000 mg/kg of α-bisabolol, once a week for three weeks.
Dose↝, intragastric administration 1000 mg/kg of α-bisabolol, once a week for three weeks.
PI3K↓, in the present study, we found that a-bisabolol inhibited Akt activation, as well as the expression of its upstream signals (PI3K, PDK1, and mTORC2).
PDK1↓,
mTORC2↑,

1259-

CAP,

Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells

in-vitro,

Lung,

H1299

in-vitro,

Lung,

A549

in-vitro,

Lung,

H23

in-vitro,

Lung,

H2009

Hif1a↓, Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein
PDK1↓,
GLUT1↓,
ROS↑,
mitResp↓,
ATP↓,

5964-

CEL,

Celecoxib pathways: pharmacokinetics and pharmacodynamics

Review,

Var,

COX2↓, purposefully designed as COX-2-selective inhibitors
*Pain↓, one of the most frequently prescribed drugs for the relief of pain and inflammation
*Inflam↓,
Apoptosis↑, proposed anticarcinogenic mechanisms of celecoxib include induction of apoptosis, cell cycle arrest, regulation of angiogenesis, and induction of endoplasmic reticulum (ER) stress.
TumCCA↑,
angioG↓,
ER Stress↑,
VEGF↓, Celecoxib treatment decreased the expression of vascular endothelial cell growth factor [53-55] and inhibition of matrix metalloproteinase 9
MMP9↓,
PDK1↓, inhibition of PDK1/Akt signaling correlated with celecoxib-induced apoptosis in both colon and prostate tumor cell lines [
Akt↓,
CA↓, Carbonic anhydrases (CA), enzymes that catalyze the reversible hydration of carbon dioxide, are also inhibited by celecoxib (IC50 in the low nanomolar range)
CardioT↑, selective COX-2 inhibitors, rofecoxib, valdecoxib, and celecoxib with an increased incidence of myocardial infarction, stroke, and death due to cardiovascular causes

5957-

CEL,

Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line

in-vitro,

Colon,

HT29

COX2↓, Celecoxib, a COX-2-specific inhibitor, has been shown to reduce the number of adenomatous colorectal polyps in patients with familial adenomatous polyposis.
PDK1↓, celecoxib induces apoptosis in the colon cancer cell line HT-29 by inhibiting the 3-phosphoinositide-dependent kinase 1 (PDK1) activity.
Apoptosis↓,

5956-

CEL,

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Review,

Var,

COX2↓, Celecoxib (Celebrex®) was developed as a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of chronic pain.
Pain↓,
CA↓, celecoxib displayed potent CA inhibitory activity in the low nanomolar range in vitro
PDK1↓, Much excitement was generated by the finding that celecoxib could bind to and inhibit PDK1
Apoptosis↑, Celecoxib is unique among the coxibs and traditional NSAIDs, because this particular drug displays the greatest potency to induce apoptotic cell death.

2398-

CGA,

Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation

in-vivo,

Col,

Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids,

PKM2↓, Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation
Glycolysis↓,
NLRP3↓,
Inflam↓, Anti-inflammatory effect of chlorogenic acid is mediated through PKM2-dependent glycolysis
HK2↓, hexokinase 2 (Hk2), pyruvate dehydrogenase kinase 1 (Pdk1) and lactate dehydrogenase A (Ldha), while CGA significantly decreased this up-regulated genes level in macrophages
PDK1↓,
LDHA↓,
GLUT1↓, significant reduction in the LPS-induced increased glucose transporter protein 1 (Glut1) mRNA
ECAR↓, Importantly, the enhanced extracellular acidification rates (ECRA), indicative of glycolysis, was rescued by CGA treatment

2781-

CHr,

PBG,

Chrysin a promising anticancer agent: recent perspectives

Review,

Var,

PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

1145-

CHr,

Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways

in-vitro,

Cerv,

HeLa

tumCV↓,
BAX↑,
BID↑,
BOK↑,
APAF1↑,
TNF-α↑,
FasL↑,
Fas↑,
FADD↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
Mcl-1↓,
NAIP↓,
Bcl-2↓,
CDK4↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
cycE1↓,
TRAIL↑,
p‑Akt↓,
Akt↓,
mTOR↓,
PDK1↓,
BAD↓,
GSK‐3β↑,
AMPK↑, AMPKa
p27↑,
P53↑,

1591-

Citrate,

The biological significance of cancer: mitochondria as a cause of cancer and the inhibition of glycolysis with citrate as a cancer treatment

Analysis,

NA,

Glycolysis↓, but the most effective inhibitor of glycolysis, which to date has not been used to fight cancer, is citrate, citric acid itself,
PDK1↓, citrate also inhibits the pyruvate dehydrogenase enzyme complex [17],
SDH↓, citrate also inhibits the succinate dehydrogenase enzyme of Krebs cycle [19].

6223-

CUR,

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects

Review,

Var,

Ferroptosis↑, including the induction of ferroptosis by regulating the SLC7A11/GPX4 axis
GutMicro↑, and modulating gut microbiota metabolism. I
Akt↓, it inhibits pro-tumorigenic signals such as Akt/mTOR, NF-κB, Wnt/β-catenin, and STAT3, thereby blocking tumor proliferation, invasion, and metastasis
mTOR↓,
NF-kB↓,
Wnt↓,
β-catenin/ZEB1↓,
STAT3↓,
TumCP↓,
TumCI↓,
TumMeta↓,
AMPK↑, activates tumor-suppressive and cytoprotective pathways, including AMPK, p53, and nuclear factor erythroid 2-related factor 2 (Nrf2), which induce cell cycle arrest and apoptosis
P53↑,
NRF2↑,
TumCCA↑,
Apoptosis↑,
Casp↑, activation of the Caspase cascade
GPx4↓, as well as ferroptosis by inhibiting the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis [5]
DNMTs↓, inhibiting epigenetic regulatory mechanisms such as DNMTs and HDACs.
HDAC↓,
VEGF↓, inhibiting VEGF signaling and enhances the immune microenvironment by improving T cell and NK cell function
Imm↑,
NK cell↑,
Warburg↓, Curcumin effectively reverses the Warburg effect and interferes with glucose metabolism by targeting HIF-1α and inhibiting key enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
Hif1a↓,
HK2↓,
PKM2↓,
LDHA↓,
GLUT1↓, as well as the functions of glucose transporter 1 (GLUT1) and monocarboxylate transporters (MCTs) [12].
MCT1↓,
AMPK↑, curcumin activates signaling pathways such as AMPK, downregulates fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1),
FASN↓,
SCD1↓,
GLS↓, Curcumin extensively intervenes in amino acid metabolism by inhibiting the activity of glutaminase (GLS), ornithine decarboxylase (ODC), and other enzymes,
Apoptosis↑, inducing apoptosis through mechanisms such as disrupting the electron transport chain, reducing membrane potential, and promoting the generation of reactive oxygen species (ROS)
ETC↓,
MMP↓,
ROS↑,
lipid-P↑, curcumin induces lipid peroxidation and collapses redox homeostasis, thereby activating the ferroptosis program [
ChemoSen↑, blocking invasion and metastasis, and enhancing chemosensitivity.
PDK1↓, In hypoxic pancreatic cancer cells, curcumin downregulates the expression of GLUT1, HK2, LDHA, and PDK1 by inhibiting the Beclin1/HIF-1α axis, which results in reduced ATP production and inhibited cell proliferation [
Beclin-1↓,
ATP↓,
Glycolysis↓, inhibiting glycolysis
GlucoseCon↓, decreased glucose uptake and increased lactate production
lactateProd↑,
MMPs↓, reduces MMP, GSH, and G6PD activities
GSH↓, inhibition of SLC7A11 to limit GSH synthesis, thereby triggering the collapse of the antioxidant defense system
G6PD↓,
OXPHOS↓, downregulate OXPHOS and glycolysis activities
SREBP2↓, curcumin treatment leads to a marked downregulation of the mRNA expression of SREBP and its target genes. inhibiting the expression of NPC1L1, SREBP-2, and HNF1α
COX2↓, curcumin exerts anti-tumor effects by downregulating the expression of NF-κB, COX-2, and AP-1
AP-1↓,
NADH↓, decreased GPx4 and FSP1 expression, induced ferroptosis by inhibiting GSH-GPx4 and FSP1-CoQ 10-NADH pathways
NRF2↑, it inhibits GPX4 and activates Nrf2 and heme oxygenase-1 (HO-1). This results in an abnormal accumulation of intracellular Fe2+, ROS, lipid peroxides, and malondialdehyde (MDA), along with a depletion of GSH
HO-1↑,
Iron↑,
MDA↑,
*ROS↓, studies have demonstrated that the topical application of curcumin on the skin exerts antitumor effects by synergistically downregulating COX-2 and ODC activities, alleviating oxidative damage, and concurrently inhibiting inflammatory proliferation i
*Inflam↓,

463-

CUR,

Curcumin induces autophagic cell death in human thyroid cancer cells

in-vitro,

Thyroid,

10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h

in-vitro,

Thyroid,

FTC-133

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

8505C

TumAuto↑,
LC3II↑,
Beclin-1↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↑, p-ERK1/2
p62↓,
p‑PDK1↓,
p‑Akt↓,
p‑p70S6↓,
p‑PIK3R1↓,
p‑S6↓,
p‑4E-BP1↓,

133-

CUR,

Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

miR-143↑, Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration.
PDK1↓, curcumin treatment inhibited PGK1 expression
FOXD3↑, Curcumin time-dependently upregulated FOXD3, which accounted for the escalating miR-143 levels with the duration of curcumin treatment.
TumCP↓, Furthermore, we showed that silencing miR-143 abrogated the effect of curcumin in inhibiting cell proliferation and migration.
TumCMig↓,
*Inflam↓, pharmaceutical properties of curcumin include antiinflammatory, antioxidant, chemo-preventative, and chemotherapeutic properties
*antiOx↑,
*chemoPv↑,
RadioS↑, underlying mechanism of curcumin in prostate cancer therapy, potentiating the clinical utility of curcumin as a chemo-preventive, chemotherapeutic, radio-, and drug-sensitizing agent.
ChemoSen↑,

1871-

DAP,

Targeting PDK1 with dichloroacetophenone to inhibit acute myeloid leukemia (AML) cell growth

in-vitro,

AML,

U937

14.0 μM

in-vivo,

AML,

mouse

TumCP↓, DAP significantly inhibited cell proliferation, increased apoptosis induction and suppressed autophagy in AML cells in vitro
Apoptosis↑,
TumCG↓, inhibited tumor growth in an AML mouse model in vivo
PDK1↓, inhibition of PDK1 with DAP
cl‑PARP↑, increased the cleavage of pro-apoptotic proteins (PARP and Caspase 3)
Bcl-xL↓, decreased the expression of the anti-apoptotic proteins (BCL-xL and BCL-2) and autophagy regulators (ULK1, Beclin-1 and Atg).
Bcl-2↓,
Beclin-1↓,
ATG3↓,
PI3K↓, DAP inhibited the PI3K/Akt signaling pathway
Akt↓,
eff↑, Importantly, 2,2-dichloroacetophenone (DAP) is a much more potent inhibitor of PDK1(than DCA). It is effective at concentrations in the micromolar (μM) range.

6686-

DAP,

Lactoferrin-encapsulated dichloroacetophenone (DAP) nanoparticles enhance drug delivery and anti-tumor efficacy in prostate cancer

in-vivo,

Pca,

mouse

PDK1↓, pplication of 2,2-dichloroacetophenone (DAP), a PDK1 inhibitor,
TumCP↓, In this study we demonstrated that DAP exhibited a superior ability to inhibit prostate cancer cell proliferation, migration and colony formation at a lower concentration (20 μM) compared to a previously established inhibitor, dichloroacetate (DCA),
TumCMig↓,
BioAv↓, However, poor aqueous solubility and lower stability of DAP limits its therapeutic application
BioAv↑, Nano formulation of DAP with natural lactoferrin enhanced its dispersion and stability by increasing polydispersity index and intensity, and reduced zeta potential values upon conjugation that overcame the solubility limitations of DAP.
Apoptosis↑, these nanoparticles induce apoptosis in cancer cells by inducing caspase3/7 activity and disrupting the glycolytic and oxidative phosphorylation pathways.
Casp3↑,
Casp7↑,
Glycolysis↓,

6684-

DAP,

GB,

Pharmacological synergism of 2,2-dichloroacetophenone and EGFR-TKi to overcome TKi-induced resistance in NSCLC cells

vitro+vivo,

NSCLC,

H1975

PDK1↓, 2,2-dichloroacetophenone (DAP) was reported as a PDK inhibitor recently, which is much more potent than dichloroacetate (DCA) in anti-cancer therapy.
eff↑, we applied DAP in combined with EGFR-TKis, erlotinib or gefitinib in NSCLC cell lines and NSCLC xenograft model. Synergistic anti-cancer effects in two NSCLC cell lines with EGFR mutation, NCI-H1975 and NCI-H1650, as well as in NCI-H1975 xenograft mo
EGFR↓, not only further suppressed the EGFR signaling in vitro and in vivo, but also significantly promoted cell apoptosis.
Apoptosis↑,

6683-

DCA,

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Review,

Var,

PDK1↓, classic DCA target, pyruvate dehydrogenase kinase
lactateProd↓, reduce lactic acid production which would push the cell towards oxidative phosphorylation: this would be the supposed function of dichloroacetate (DCA).
Apoptosis↑, They found that DCA induced apoptosis and decreased proliferation by restoring mitochondrial oxidative metabolism, without toxicity to normal cells.
TumCP↓,
selectivity↑,
other↝, many clinics, usually called “DCA Clinics” have opened, mainly in Canada and Germany.
Dose↝, DCA is sold over the counter and is produced by many laboratories. The quality of the product from these laboratories is not well established. These particulars explain many of the doubts about DCA’s real value as a therapeutic tool.
BioAv↑, DCA is an orally available molecule that is quickly and almost completely absorbed by the digestive system
Half-Life↓, With a 10 mg/kg infusion the maximum plasma concentration achieved was between 19.9 μg/ml and 24.7 μg/ml with a half life of only 20 minutes. If the infused dose was increased to 20 mg/kg the plasma concentration was between 57.3 and 74.9 μg/ml with
Glycolysis↓, facilitates the switch from a glycolytic to an oxidative metabolism.
OXPHOS↑,
Casp↑, onversion to an oxidative metabolism by DCA, is an increase in caspase-mediated apoptosis
i-pH↓, pHi decreases (at least temporarily).
COX2↑, DCA increases the expression of COX2 and the latter increases tumor resistance to DCA. Therefore, a possible integrated treatment could be COX2 inhibitor co-administered with DCA
Hif1a↓, DCA suppresses HIF-1α activity and angiogenesis through the inhibition of PDK-II
angioG↓,
HMG-CoA↓, figure 7
GSTZ1↓,
OCR↑,
lipoGen↓,
fatigue↓,
survivin↓, Survivin (an inhibitor of apoptosis) expression was decreased and miR-375 (a microRNA which acts as a tumor suppressor) levels were increased.
miR-375↑,
eff↓, African Americans are known to respond poorly to therapy compared with Caucasian American patients.
CSCs↓, DCA can inhibit the cancer stem cell like characteristics of the cells and strongly influenced the metabolic pathway of the cells causing a shift from glycolysis to oxidative phosphorylation.
TumAuto↑, DCA induced autophagy in human colon cancer cells with ROS production and mTOR inhibition,
mTOR↓,
TumCI↓, DCA induced apoptosis, inhibited invasion, and angiogenesis. In mouse experiments in vivo with the melanoma allografts, DCA reduced volume and weight of tumors.
TumVol↓,
TumW↓,
ATP↓, DCA alone reduced glycolytic activity and intracellular ATP levels and inhibited cellular growth in melanoma cells.
Warburg↓, DCA was also found to interrupt the Warburg effect and decreased proliferation.
eff↑, The co-application of metformin and DCA suppressed human liver cancer cell proliferation inducing apoptosis through inhibition of mTORC1 and increased ROS in vitro and in vivo
e-pH↑, when measuring extracellular pH in vivo found that an initial increase in extracellular pH of tumors in mice when treated with DCA.
eff↑, To avoid the development of this type of metabolic resistance DCA should be given simultaneously with other metabolic drugs such as metformin [327] or 2 deoxyglucose.
eff↑, chronic co-administration of DCA with sodium bicarbonate to tumor bearing mice prolonged survival
other↝, High doses of thiamin (vit B1) have effects similar to those of DCA: reduced PDH phosphorylation, reduced lactate prod and increased casp3 activity with reduced proliferation in colon cancer cells. can vitB1 replace DCA as a nontoxic PDK inhibitor?
RadioS↑, Dong et al. [380] found that DCA radiosensitized esophageal carcinoma cells in vitro and in vivo through increased ROS accumulation.
toxicity↓, 25 mg/Kg/day may show a mild sedative effect or drowsiness. The most serious published side effect is reversible peripheral neuropathy
Dose↝, 10 to 50 mg/kg body weight/day has been found to be a safe dose. However, single nucleotide polymorphisms (SNPs) in the gene of the enzyme GSTZ1 cause difficulties in establishing a universal dose [409] as noted above.
eff↑, There is strong evidence showing that the association of metformin and DCA has significant cytotoxic effects.
eff↑, To this approach we must add a third compound: a COX2 inhibitor like celecoxib to decrease COX2 expression induced by DCA.
eff↑, the triple association of DCA, metformin and celecoxib, which has never been experimentally tested in patients, deserves well planned phase II clinical trials.
toxicity↝, DCA will never become a stand-alone chemotherapeutic compound. The fundamental reason for this statement is that the drug can only reach micromolar blood concentrations without toxicity and requires millimolar levels to be cytotoxic.
eff↓, DCA should not be used in association with allopurinol, NSAIDs, or flavonoids because they reduce cellular DCA uptake.

6682-

DCA,

QC,

Dichloroacetate and Quercetin Prevent Cell Proliferation, Induce Cell Death and Slow Tumor Growth in a Mouse Model of HPV-Positive Head and Neck Cancer

in-vivo,

HNSCC,

MEER

mouse

PDK1↓, Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase that decreases lactate production.
lactateProd↓,
GlucoseCon↓, Quercetin is a flavonoid compound found in fruits and vegetables that inhibits glucose uptake and lactate export.
tumCV↓, Both DCA and quercetin inhibited colony formation and reduced cell viability, which were associated with mTOR inhibition and increased apoptosis through enhanced ROS production.
mTOR↓,
Apoptosis↑,
ROS↑,
TumCG↓, DCA and quercetin reduced tumor growth and enhanced survival in immune-competent mice, correlating with decreased proliferation as well as decreased acidification of the tumor microenvironment and reduction of Foxp (+) Treg lymphocytes.
pH↑,
cl‑PARP↑, increased levels of cleaved PARP (Figure 2C) in the combination treatment as well as increased caspase 3 cleavage
Casp3↑,
DNAdam↑, DCA and Quercetin Increase DNA Damage through Enhanced ROS Production
p‑γH2AX↑, increased ROS production was correlated with increased phosphorylated H2AX, which is an indicator of ROS-induced DNA damage
eff↓, NAC can partially prevent the DCA/quercetin increased ROS production and phosphorylation of H2AX, as well as the induction of cleaved PARP.
OS↑, In addition to just prolonging survival, DCA, quercetin, and more so their combination, increased the number of animals who went on to be tumor-free.

6681-

DCA,

Dichloroacetate (DCA) in Cancer Care

PDK1↓, Specifically, it inhibits pyruvate dehydrogenase kinase, which may convert metabolism from fermentative glycolysis back to oxidative phosphorylation.
Apoptosis↑, This process may induce cancer cell apoptosis through several mechanisms including increased oxidative stress and reduced lactate levels.
ROS↑,
lactateProd↓,
Dose↝, DCA can be administered orally or intravenously.
eff↝, overall, there is insufficient evidence to support the efficacy of DCA as a cancer treatment.
toxicity↓, most studies have found DCA to be reasonably safe and well tolerated, The most common side effect is reversible peripheral neuropathy.
NP/CIPN↑, One of the five patients who entered the trial with some degree of peripheral neuropathy developed a score of 3 in the Total Neuropathy Score (TNS), but this resolved within six months after DCA cessation
Dose↝, doses range from 10-50mg/kg daily, with the most common oral dosing being 6.25-12.5mg/kg taken twice daily.
*BioAv↑, DCA is a small water soluble molecule of 150 Da, allowing it to achieve 100% bioavailability when given either orally or intravenously
*Half-Life↓, Serum DCA levels rise rapidly after oral administration and exhibit a relatively short half-life. elimination half-life of 92 minutes
GSTZ1↝, DCA metabolism is affected by glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI) genotype status. Individuals with at least one wild-type haplotype metabolize DCA more rapidly and thus may be able to tolerate a higher dose
Glycolysis↓, DCA acts on the mitochondrial matrix of cancer cells, diverting metabolism from fermentative glycolysis back to oxidative phosphorylation
OXPHOS↑,
MPT↑, reopening of voltage and redox sensitive mitochondrial transition pores (22). This allows for the pro-apoptotic mediators, cytochrome c and apoptosis-inducing-factor, to be released into the cytoplasm,
Cyt‑c↑,
AIF↑,
Casp↑, increasing the levels of pro-apoptotic ROS through the activation of caspases
CSCs↓, Although less well established, there is some evidence that DCA may be able to reduce stemness and induce differentiation in cancer stem cells
Remission↑, rigorous treatment cycle with DCA, alpha lipoic acid, and B vitamins and achieved complete remission of his cancer as evidenced by PET scans, CT scans, and laboratory testing. Four years later, the patient remained cancer free.
ChemoSen↑, Several preclinical studies have demonstratedsynergistic effects of DCA with chemotherapeutic agents, including carboplatin (34, 57), oxaliplatin (34, 57), 5-fluorouracil (29), paclitaxel (58, 59), doxorubicin (60), elesclomol (24), and sorafenib (6
RadioS↑, There is preliminary preclinical evidence that DCA may act as a radiosensitizer primarily by increasing levels of reactive oxygen species in tumour cells
toxicity↑, Combined with artesunate one patient experienced fatal liver and bone marrow toxicity.

6679-

DCA,

GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial

Trial,

Melanoma,

PDK1↓, Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK).
Half-Life↝, The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant.
eff↑, Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1.
NP/CIPN↑, This patient displayed the strongest response, but also the strongest neuropathy.
Dose↝, single oral dose of 25 mg/kg taken at approximately 9 am.
Half-Life↝, DCA was then cleared with a mean half‐life of 93 min (Table 2), with 90% of the drug being cleared by 6 hours, and DCA being undetectable at 24 hours

6678-

DCA,

Cisplatin,

Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma

Trial,

HNSCC,

double-blind phase II study added DCA to cisplatin-based CRT in patients with LA-HNSCC.

PDK1↓, Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously.
OS∅, end-of-treatment complete response rates were significantly higher in the DCA group compared to placebo (71.4% vs 37.5%, p = 0.0362), survival outcomes were not significantly different between groups.
lactateProd↓, significant drop in pyruvate (0.47, p <0.005) and lactate (0.61, p <0.005) in the DCA group.
toxicity↝, Adding DCA to cisplatin-based CRT appears safe with no detrimental effect on survival and expected metabolite changes compared to placebo.
FAO↑, DCA treated patients had enhanced fatty acid oxidation, and increased mitochondrial oxidation that may contribute to unique microbiome-related changes.

5196-

DCA,

Dichloroacetate induces apoptosis in endometrial cancer cells

in-vitro,

Var,

selectivity↑, Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells.
MMP↓, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism.
survivin↓,
Ca+2↓, DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway.
P53↑, DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism.
PDK1↓, DCA binds to PDK and attenuates inhibition of PDH activity.
PDH↑,
Glycolysis↓, The increased PDH activity shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential (MMP) hyperpolarization
OXPHOS↑,
ROS↑, translocation of reactive oxygen species (ROS) and cytochrome c from the mitochondria to the cytoplasm, subsequently inducing apoptosis through the activation of caspases
Cyt‑c↑,
Apoptosis↑,
Casp↑,
tumCV↓, DCA Reduces Endometrial Cancer Cell Viability in a Dose-Dependent Manner
PUMA↑, DCA Increases PUMA Expression

5197-

DCA,

5-FU,

Dichloroacetate attenuates hypoxia-induced resistance to 5-fluorouracil in gastric cancer through the regulation of glucose metabolism

in-vitro,

GC,

tissues from 10 patients with gastric cancer who had different responses to adjuvant 5-FU treatment.

Glycolysis↓, dichloroacetate (DCA), an inhibitor of the glycolytic pathway.
ChemoSen↑, DCA treatment was able to re-sensitize gastric cancer cells with hypoxia-induced resistance to 5-FU through the alteration of glucose metabolism.
PDK1↓, Dichloroacetate (DCA) is a well-known inhibitor of PDK

1864-

DCA,

MET,

Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells

in-vitro,

BC,

MCF7

DCA (2.5 mM) and metformin (1 mM)

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.

1608-

EA,

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity

in-vitro,

Cerv,

HeLa

35 μg/mL

in-vitro,

Liver,

HepG2

220ug/mL

in-vitro,

BC,

MCF7

75 ug/mL

in-vitro,

Lung,

A549

242um/mL

in-vitro,

Nor,

HUVECs

258um/mL

eff↑, Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW
Dose∅, EA inhibited HeLa cells with an IC50 of 35 μg/mL
*BioAv↑, EA is not sensitive to high temperatures and is not highly soluble in many solvents.
selectivity↑, selectivity index varied from 7.4 for Hela to about 1 for A549
TumCP↓, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
Casp↑, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
PTEN↑,
TSC1↑,
mTOR⇅,
Akt↓, AKT, PDK1 expression were down-regulated
PDK1↓,
E6↓, mRNA levels of E6/E7 were determined to decrease gradually with the increase in EA incubation time and concentration
E7↓,
DNAdam↑, When DNA damage is introduced into cells from exogenous or endogenous sources there is an increase in the amount of intracellular reactive oxygen species (ROS)
ROS↑,
*BioAv↓, EA cannot be exploited for in vivo therapeutic applications in the current situation because of its poor water solubility and accordingly low bioavailability.
*BioEnh↑, As Lei [52] reported that EA in pomegranate leaf is rapidly absorbed and distributed as well as eliminated in rats
*Half-Life∅, blood concentration peaked at 0.5 h with Cmax = 7.29 μg/mL, and the drug concentration decreased to half of the original after 57 min of administration

6779-

EGCG,

Effectiveness of epigallocatechin gallate nanoparticles on the in-vivo treatment of Alzheimer's disease in a rat/mouse model: a systematic review

Review,

AD,

*BioAv↑, EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG.
*ROS↓, Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats.
*AChE↓,
*Dose↝, formulated nanoparticles were given at a dose of 10 mg/kg. (rats)
*neuroP↑, Neuroprotective mechanisms of EGCG nanoformulations
*APP↓, Treating the AD rats with nanoEGCG significantly reduced the levels of APP, Aβ1–42, AChE, and GSK3β and elevated PDK1 levels
*GSK‐3β↓,
*PDK1↓,
*BBB↑, EGCG nanoparticles demonstrated better BBB penetration ability, higher bioavailability, and enhanced improvement of memory deficits over free EGCG in experimental animal models.
*memory↑,

6388-

Eug,

Eugenol’s anti-cancer properties, its modulation of signalling pathways, and cascades across various cancers: A review

Review,

Var,

Dose↝, Eugenol, a significant bioactive compound, is found in cloves and other traditional Indian medicinal plants, such as cinnamon, tulsi, ginger, turmeric, and Japanese star anise, which have been reported to have significant anticancer properties.
AntiCan↑,
*Inflam↓, also exhibits different pharmacological effects (anti-inflammatory, cardio-protection, and neuroprotection).
*cardioP↑,
*neuroP↑,
angioG↓, eugenol exhibits anti-apoptotic, anti-angiogenic, and anti-metastatic properties in cancer cell lines and in vivo animal models, which we discuss in this review.
TumMeta↓,
*BioAv↑, Oral administration of eugenol promoted rapid absorption by different organs and metabolism in the liver. encapsulation is required to address the issues of early absorption, increased water solubility, and improved efficiency
*eff↑, Eugenol encapsulation as an inclusion with β-cyclodextrin, chitosan, and 2-hydroxypropyl-β-cyclodextrin nanoparticles improves its thermal stability
*toxicity↝, Eugenol at lower doses displayed minimal adverse effects, including contact dermatitis, local irritation, and rare allergic responses. However, at its higher doses, it can lead to liver and kidney damage, tissue injury, sudden onset of seizures, and
antiNeop↑, exhibit antineoplastic properties against different cancers by triggering cell cycle arrest and apoptosis in cancer cells
TumCCA↑,
Apoptosis↑,
*antiOx↑, Eugenol exhibits its antioxidant property due to its unique structural configuration, specifically the presence of an allyl group, as revealed by electron spin resonance
*lipid-P↓, Eugenol prevents lipid peroxidation (Nagababu and Lakshmaiah 1994), hexanal oxidation (Lee and Shibamoto 2001), copper-dependent LDL oxidation, and nonenzymatic peroxidation in liver mitochondria
*ROS↓, Eugenol exhibited 58–81 % DPPH radical scavenging potential in its 0.25–1.0 µM/ml concentration
*SOD↑, Eugenol protects against oxidative damage by increasing the levels of certain antioxidant enzymes, such as SOD, CAT, GST, and GPx (Huang et al. 2015).
*Catalase↑,
*GSTs↑,
*GPx↑,
*iNOS↓, Eugenol pre-treatment increased the levels of antioxidant enzymes and decreased the expression of iNOS, COX2, IL-6, and tumor necrosis factor-α (TNF-α) (Kaur et al. 2010).
*COX2↓,
*IL6↓,
*TNF-α↓,
*AntiArt↑, Administration of eugenol at 33 mg/kg dose in arthritis-induced male Sprague-Dawley rats decreased the swelling of paws and joints (
*Bacteria↓, Along with cinnamaldehyde and thymol, Li et al. determined eugenol's antibacterial activity against E. coli and S. aureus.
TumAuto↑, eugenol activated apoptosis and autophagy through the PI3K/AKT/FOXO3a pathway in cancer cells(breast cancer cells).
PI3K↓, PI3K/Akt/mTOR pathway inhibition
Akt↓,
FOXO3↝,
BAX↑,
mTOR↓, PI3K/Akt/mTOR pathway inhibition
NF-kB↓, NF-κB signaling pathway inhibition
P53↑, In some cancers, eugenol has been shown to upregulate p53, thereby inhibiting cancer growth.
TumCG↓,
CSCs↓, eugenol downregulated certain signaling cascades of the Wnt signaling pathway and specific cancer stem cell markers, including CD44, EpCAM, Notch1, and Oct4, in breast cancer cell lines treated with eugenol.
CD44↓,
EpCAM↓,
NOTCH1↓,
OCT4↓,
Bcl-2↓, Eugenol also downregulates the protein expressions of p85, BCL-2, PDK1, HER2, AKT, BAD, Cyclin D1, and NF-KB.
PDK1↓,
HER2/EBBR2↓,
BAD↓,
cycD1/CCND1↓,
ROS↑, EUG-medium chain triglyceride nanoemulsions Liver cancer HB8065 cells Increased the levels of ROS generation to initiated the apoptotic cell death
Casp3↑, apoptosis initiated by Caspase-3 protein upregulation
selectivity↑, Eugenol was not cytotoxic to MCF10A cells; however, it displayed cytotoxic activity in the transformed MCF10A cells (MCF10A-ras).
MMP2↓, A significant decline in matrix metalloproteinase (MMP-2, MMP-9) levels and an increase in tissue inhibitor of metalloproteinase-1 (TIMP-1) expression were also observed.
MMP9↓,
TIMP1↑,
VEGF↓, Eugenol also inhibits metastatic invasion and angiogenesis, as evident from the downregulation of MMP-2, MMP-9, VEGF, and VEGFR1, along with the upregulation of RECK and TIMP-2
VEGFR1↓,
RECK↑,
TIMP2↑,
DNAdam↑, Eugenol demonstrated an apoptosis-inducing effect in HL-60 cells, as evidenced by DNA fragmentation and a DNA ladder assay.
MMP↓, It is accompanied by a decline in mitochondrial membrane potential and thiol levels, early disruption of the lipid layer, DNA fragmentation, and activation of proapoptotic markers (Caspase-3, PARP, p53)
Thiols↓,
PARP↑,
*Pain↓, eugenol nanoemulsion may significantly reduce pain-associated arteriovenous fistula (AVF)
E2Fs↓, t interferes with several critical cancer signaling pathways, including the Wnt/b-Catenin pathway, PI3K/AKT pathway, MAPK/ERK pathway, E2F1/survivin pathway, JNK/STAT3 pathway, and NF-κB signaling pathway, among others.
survivin↓, cause E2F1/survivin downregulation, which activates apoptosis in breast cancer cells

6337-

Eug,

Eugenol alleviated breast precancerous lesions through HER2/PI3K-AKT pathway-induced cell apoptosis and S-phase arrest

in-vitro,

BC,

MCF-10AT

TumCP↓, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%,
TumCCA↑, Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest
HER2/EBBR2↓, In MCF-10AT cells treated by 180 μM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased
Akt↓,
PDK1↓,
Bcl-2↓,
NF-kB↓,
BAD↓,
cycD1/CCND1↓,

960-

HNK,

Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth

vitro+vivo,

BC,

MCF7

HNK (diluted in DMSO, 25 mg/kg/day

mice

vitro+vivo,

BC,

MDA-MB-231

0-40uM/24hr

OCR↑, which resulted in an increase in OCR and a decrease in ECAR, glucose uptake, lactic acid production and ATP production.
ECAR↓,
GlucoseCon↓, decreased glucose uptake, lactate production and ATP production in cancer cells.
lactateProd↓,
ATP↓,
Glycolysis↓,
Hif1a↓,
GLUT1↓,
HK2↓,
PDK1↓,
Apoptosis↑,
LDHA↓, upregulation of LDHA mediated by HIF-1α promoted the formation of lactic acid from pyruvate, which contributed to the acidification of the tumor microenvironment. Our experimental observation results showed that these changes were reversed by HNK

998-

PB,

Phenyl butyrate inhibits pyruvate dehydrogenase kinase 1 and contributes to its anti-cancer effect

in-vivo,

NA,

zebrafish and wild type mice

p‑PDH↓,
PDH↑,
PDK1↓,
HDAC↓,
Glycolysis↓, decreased glycolysis in cytoplasm
MMP↓,
Apoptosis↑,

2044-

PB,

DCA,

Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate

in-vivo,

NA,

mice

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↑,

2380-

PBG,

Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy

Review,

Var,

Hif1a↓, Flavonoid components from propolis, as inhibitors of HIF-1, have the ability to regulate critical glycolytic components in cancer cells, including (PKM2), (LDHA), (GLUTs), (HKII), (PFK-1), and (PDK)
Glycolysis↓,
PKM2↓,
LDHA↓,
GLUT2↓,
HK2↓,
PFK1↓,
PDK1↓,
chemoP↓, The positive effects of combining propolis with chemotherapeutics include reduced cytotoxicity to peripheral blood leukocytes, liver, and kidney cells.
radioP↑, Their selective nature makes them suitable for protecting normal cells while inducing cell death in cancer cells during chemotherapy or radiotherapy.

2471-

RES,

Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression

in-vivo,

Diabetic,

rats

*p‑PDK1↓, RSV treatment significantly downregulated the proteins expression of p-PDK1 and p-AKT (P < 0.01) and the levels of HIF-1α (P < 0.05) and GLUT1 (P < 0.01), while significantly upregulating the level of LDLR (P < 0.05).
*p‑Akt↓,
*Hif1a↓,
*GLUT1↓,

2472-

RES,

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

in-vivo,

Nor,

rat

*SIRT1↑, However, resveratrol treatment along with resuscitation fluid restored SIRT1 activity.
*PGC-1α↑, When resveratrol was administered 10 min after the start of resuscitation, the protein level of SIRT1, PGC-1α and c-Myc in the nuclear fraction was restored.
*cMyc↑,
*PDK1↓, The experiments demonstrated a significant increase in PDK1 after T-H, which was abolished by resveratrol treatment

2469-

SK,

Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2

in-vitro,

Lung,

H1975

0-8uM

Apoptosis↑, Shikonin induced cell apoptosis and pyroptosis by triggering the activation of the caspase cascade and cleavage of poly (ADP-ribose) polymerase and gasdermin E by elevating intracellular ROS levels
Pyro↑,
Casp↑,
cl‑PARP↑,
GSDME↑,
ROS↑,
COX2↓, shikonin induced the degradation of COX-2 via the proteasome pathway, thereby decreasing COX-2 protein level and enzymatic activity and subsequently inhibiting the downstream PDK1/Akt and Erk1/2 signaling pathways through the induction of ROS produc
PDK1↓,
Akt↓,
ERK↓,
eff↓, Notably, COX-2 overexpression attenuated shikonin-induced apoptosis and pyroptosis
eff↓, NAC pre-treatment inhibited the shikonin-induced activation of the caspase cascade (caspase-8/9/3) and cleavage of PARP and GSDME in H1975 cells
eff↑, Celecoxib augmented the cytotoxic effects of shikonin by promoting the apoptosis and pyroptosis of H1975 cells

2470-

SK,

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism

in-vitro,

Lung,

H1299

PKM2↓, Base on this, we designed a series of novel shikonin (SK) thioether derivatives as PKM2/PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory
PDK1↓,
Glycolysis↓, E5 could significantly inhibit the proliferation and aerobic glycolysis of NSCLC cell

Showing Research Papers: 1 to 50 of 56
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 56

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2, Catalase↑, 2, GPx↑, 2, GSTs↑, 1, lipid-P↓, 1, MDA↓, 1, ROS↓, 4, SOD↑, 2,

Mitochondria & Bioenergetics(tgid=3) ⓘ

PGC-1α↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↑, 1, Glycolysis↑, 1, PDK1↓, 2, p‑PDK1↓, 1, SIRT1↑, 1,

Cell Death(tgid=5) ⓘ

p‑Akt↓, 1, iNOS↓, 2,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

GSK‐3β↓, 1,

Migration(tgid=13) ⓘ

APP↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1, GLUT1↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 2, IL6↓, 1, Inflam↓, 5, NF-kB↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 4, BioEnh↑, 1, Dose↝, 1, eff↑, 1, Half-Life↓, 1, Half-Life∅, 1,

Clinical Biomarkers(tgid=22) ⓘ

AST↓, 1, IL6↓, 1,

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 1, chemoPv↑, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 3, Pain↓, 2, toxicity↝, 1, toxicity∅, 1,

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,
Total Targets: 46

Scientific Paper Hit Count for: PDK1, Pyruvate dehydrogenase kinase 1

9 Dichloroacetate
6 Baicalein
4 Betulinic acid
3 Celecoxib
3 Chrysin
3 Curcumin
3 Dichloroacetophenone(2,2-)
3 Vitamin C (Ascorbic Acid)
2 5-fluorouracil
2 Berberine
2 Propolis -bee glue
2 Eugenol
2 Phenylbutyrate
2 Resveratrol
2 Shikonin
1 Alpha-Lipoic-Acid
1 Baicalin
1 α-Bisabolol / Chamomile oil
1 Capsaicin
1 Chlorogenic acid
1 Citric Acid
1 gefitinib, erlotinib
1 Quercetin
1 Cisplatin
1 Metformin
1 Ellagic acid
1 EGCG (Epigallocatechin Gallate)
1 Honokiol
1 Selenite (Sodium)
1 Thymoquinone
1 Wogonin

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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:246  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

PDK1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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