DNA-PK Cancer Research Results

DNA-PK, DNA-dependent protein kinase: Click to Expand ⟱
Source:
Type:
DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic kinase involved in DNA repair and transcriptional regulation. DNA-PK is deregulated in selected cancer types and is strongly associated with poor outcome.

Elevated levels of DNA-PK have been observed in various cancers, including breast cancer, lung cancer, and liver cancer. High expression levels are often associated with aggressive tumor characteristics and poor prognosis.
Conversely, low expression of DNA-PK may be linked to increased sensitivity to certain therapies, particularly those that induce DNA damage, such as radiation and some chemotherapeutic agents.
Scientific Papers found: Click to Expand⟱
234- AL,    Allicin Induces Anti-human Liver Cancer Cells through the p53 Gene Modulating Apoptosis and Autophagy
- in-vitro, HCC, Hep3B
ROS↑, increased the production of ROS levels at 1, 3, 6 h. I
*toxicity∅, In other study, allicin treatment did not increase the leakage of lactate-dehydrogenase (LDH) of primary rat hepatocytes until 1 mM allicin treated with rat hepatocytes24. For this reason, allicin could be inferred as safe to normal liver cells
MMP↓, Allicin decreased mitochondrial membrane potential
BAX↑,
Bcl-2↓,
AIF↑,
Casp3↑, protein expression levels of caspase-3, -8, -9 increased after allicin treatment
Casp8↑,
Casp9↑,
eff↓, Allicin significantly induced ROS overproduction, whereas NAC pretreatment decreased the ROS induction by allicin exposure in Hep 3B cells
γH2AX↑, significant increase in the expression of γ-H2AX was observed at the initial stages (3, 6 h), but not at the later stages of 12, 24, 48 h
selectivity↑, data suggested that allicin induced apoptosis in p53-deficiency human liver carcinoma cells but caused autophagy in p53-normal function human liver carcinoma cells.
DNA-PK↑, increases production of ROS, triggers DNA damage

1361- Ash,  SRF,    Withaferin A, a natural thioredoxin reductase 1 (TrxR1) inhibitor, synergistically enhances the antitumor efficacy of sorafenib through ROS-mediated ER stress and DNA damage in hepatocellular carcinoma cells
- in-vitro, Liver, HUH7 - in-vivo, Liver, HUH7
TrxR↓, TrxR1
ROS↑,
DNA-PK↑,
ER Stress↑,
Apoptosis↑,
eff↓, Pre-treatment with the antioxidant NAC significantly inhibited ROS generation, ER stress, DNA damage, and apoptosis induced by Sora/WA co-treatment

1978- CUR,    Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells
- in-vitro, Cerv, HeLa
TrxR1↓, curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells
ROS↑,
DNA-PK↑, subsequently induces DNA oxidative damage
eff↑, curcumin-pretreated HeLa cells are more sensitive to oxidative stress
Trx↓, down-regulates Trx1 level and decreases Trx activity in HeLa cells
Trx1↓,

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.


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 4,   Trx↓, 1,   Trx1↓, 1,   TrxR↓, 1,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

lactateProd↓, 1,   p‑PDH↑, 1,   PDK1↓, 1,   PDKs↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

DNA Damage & Repair ⓘ

DNA-PK↑, 4,   cl‑PARP↑, 1,   γH2AX↑, 2,  

Drug Metabolism & Resistance ⓘ

Dose∅, 1,   eff↓, 2,   eff↑, 2,   selectivity↑, 2,  
Total Targets: 26

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity∅, 2,  
Total Targets: 1

Scientific Paper Hit Count for: DNA-PK, DNA-dependent protein kinase
1 Allicin (mainly Garlic)
1 Ashwagandha(Withaferin A)
1 Sorafenib (brand name Nexavar)
1 Curcumin
1 Dichloroacetate
1 Metformin
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#:399  State#:%  Dir#:2
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