PDKs Cancer Research Results

PDKs, pyruvate dehydrogenase kinase: Click to Expand ⟱
Source:
Type:
– PDK1 is often upregulated in cancers and is central to the metabolic reprogramming (Warburg effect) that allows tumor cells to favor glycolysis over oxidative phosphorylation.
– Elevated PDK1 expression has been correlated with aggressive tumor behavior and poor prognosis in several cancer types, including non‐small cell lung cancer, ovarian cancer, and gastric cancer.

– Although PDK2 has a similar catalytic role as PDK1, its expression levels and impact may vary.
– Some studies have observed that increased PDK2 expression is associated with more aggressive cancer features and resistance to therapy in certain tumor types.

– PDK3 is often upregulated in response to hypoxic conditions—a common feature of solid tumors—which can further drive metabolic divergence in cancer cells.

– The role of PDK4 appears to be more variable. In some settings, its activity might be lower in tumor cells to favor the use of glycolysis, while in others, it may be upregulated as part of broader metabolic adaptations.

-By upregulating PDKs, cancer cells limit the flux of pyruvate into the mitochondria, thereby promoting glycolysis.
Scientific Papers found: Click to Expand⟱
5195- DCA,  Rad,    Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells
- in-vitro, BC, 4T1 - in-vitro, BC, EMT6
PDKs↑, Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which leads to enhanced reactive oxygen species (ROS) production.
ROS↑, Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells
p‑PDH↓, hypoxic conditions. As expected, DCA treatment decreased phosphorylated pyruvate dehydrogenase (PDH) and lowered both extracellular acidification rate (ECAR) and lactate production.
ECAR↓,
lactateProd↓,
selectivity↓, Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells
RadioS↑, Consistently, DCA radiosensitized hypoxic tumor cells and 3D spheroids while leaving the intrinsic radiosensitivity of the tumor cells unchanged.

6419- MEL,    The potential influence of melatonin on mitochondrial quality control: a review
- Review, Nor, NA
*mt-ACC⇅, Melatonin regulates pyruvate or fatty acid metabolism to increase the concentration of acetyl-CoA in mitochondria. these studies indicate that melatonin increases or decreases acetyl-CoA content in mitochondria to regulate mitochondrial metabolism.
*PKM1↑, melatonin increases the activity of pyruvate kinase M1/2 (PKM) to regulate glycolysis
*PKM2↑,
*Glycolysis↝,
*PDKs↑, melatonin activates pyruvate dehydrogenase kinase 4 (PDK4) to regulate acetyl-CoA content
*FAO↑, melatonin can promote fatty acid metabolism by directly enhancing β-oxidation or increasing the transfer of fatty acid-derived acetyl-CoA into mitochondria
*ETC↑, Second, melatonin can enhance the activity of the electron-transport chain (ETC) and oxidative phosphorylation (OXPHOS) to regulate mitochondrial metabolism.
*OXPHOS↑,
*ATP↑, melatonin enhanced OXPHOS and promoted adenosine triphosphate (ATP) synthesis in rat brain and liver mitochondria
Glycolysis↓, ome studies have found that melatonin drove the switch from cytosolic glycolysis to mitochondrial OXPHOS in cancer cells
OXPHOS↑,
*Ca+2↓, melatonin can regulate the membrane potential of mitochondria and decrease excessive calcium levels to enhance ETC activity to increase ATP production
*ROS↓, Melatonin exhibits superior antioxidant ability. Melatonin, as a major scavenger of reactive oxygen species (ROS), may play a pivotal role in protecting mitochondria from ROS-induced injury
*antiOx↑, These specific characteristics make melatonin a broad-spectrum antioxidant.
*SOD2↑, melatonin can upregulate the expression of superoxide dismutase (MnSOD), glutathione peroxidase (GSH-Px) and catalase (CAT) to prevent cell stress and injury
*GPx↑,
*Catalase↑,
*MFN1↑, On the one hand, melatonin increases mitochondrial fusion-related genes such as mitofusin-1 (Mfn1), mitofusin-2 (Mfn2) and optic atrophy1 (Opa1) to promote mitochondrial fusion
*MFN2↑,
*OPA1↑,
*YAP/TEAD↑, studies have found that melatonin activated the Yap-Hippo pathway to increase Opa1-related fusion
*Hippo↑,
*SIRT1↑, melatonin alleviated cardiac dysfunction induced by diabetes by upregulating SIRT1-PGC1α to inhibit the expression of Drp1
*PGC-1α↑,
*DRP1/DNM1L↓,


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

OXPHOS↑, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ECAR↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   p‑PDH↓, 1,   PDKs↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

RadioS↑, 1,   selectivity↓, 1,  
Total Targets: 9

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   MFN1↑, 1,   MFN2↑, 1,   OPA1↑, 1,   OXPHOS↑, 1,   ROS↓, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,   DRP1/DNM1L↓, 1,   ETC↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

mt-ACC⇅, 1,   FAO↑, 1,   Glycolysis↝, 1,   PDKs↑, 1,   PKM1↑, 1,   PKM2↑, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Hippo↑, 1,   YAP/TEAD↑, 1,  

Migration(tgid=13) ⓘ

Ca+2↓, 1,  
Total Targets: 23

Scientific Paper Hit Count for: PDKs, pyruvate dehydrogenase kinase
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#:1201  State#:%  Dir#:2
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