PKA Cancer Research Results
PKA, protein kinase A: Click to Expand ⟱
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Protein kinase A (PKA)
• PKA is composed of regulatory (R) and catalytic (C) subunits. Binding of cAMP to the regulatory subunits releases the catalytic subunits, which then phosphorylate target proteins.
– Increased PKA activity has been associated with the activation of downstream signaling pathways that promote cell growth and survival.
– Thus, the level of PKA activation (often indirectly inferred by phosphorylation status of downstream targets) can serve as a marker for tumor progression and treatment resistance.
– PKA does not act in isolation—it interacts with other signaling pathways (e.g., MAPK, PI3K/AKT).
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Scientific Papers found: Click to Expand⟱
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in-vitro, |
BC, |
SUM159 |
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in-vitro, |
BC, |
4T1 |
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PI3K↑, FMD activates PI3K-AKT, mTOR, and CDK4/6 as survival/growth pathways, which can be targeted by drugs to promote tumor regression.
Akt↑,
mTOR↑,
CDK4↑,
CDK6↑,
hyperG↓, FMD cycles also prevent hyperglycemia and other toxicities caused by these drugs.
TumCG↓, cycles of FMD significantly slowed down tumor growth, reduced tumor size, and caused an increased expression of intratumor Caspase3
TumVol↓,
Casp3↑,
BG↓, confirming our hypothesis that lowering intracellular glucose levels (through reduced extracellular levels or reduced uptake) reduces CSC survival
eff↑, 2DG potentiated the effect of FMD both in terms of delaying tumor progression and in decreasing the number of mammospheres derived by tumor masses,
eff∅, metformin did not show any additive or synergistic antitumor effect when combined with the FMD, thus suggesting that FMD and metformin have redundant effects on blood glucose levels
PKA↓, We have previously shown that prolonged fasting reduces the activity of protein kinase A (PKA) in different types of normal cells
KLF5↓, PKA inhibition resulted in the downregulation of KLF5, a potential therapeutic target for TNBC
p‑GSK‐3β↑, (GSK3β) phosphorylation
Nanog↓, stemness-associated genes NANOG and OCT4, and KLF2 and TBX3,
OCT4↓,
KLF2↓,
eff↑, Combining FMD cycles with PI3K/AKT/mTOR inhibitors results in long-term animal survival and reduces treatment-induced side effects
ROS↑, FMD resulted in an increased expression of pro-apoptotic molecules, such as BIM, and ASK1, a critical cellular stress sensor frequently activated by ROS, whose production was previously shown to be increased by the FMD
BIM↑,
ASK1↑,
PI3K↑, FMD cycles upregulate PI3K-AKT and mTOR pathways and downregulate CCNB-CDK1 while upregulating CCND-CDK4/6 signaling axes
Akt↑,
mTOR↑,
CDK1↓,
CDK4↑,
CDK6↑,
eff↑, combining STS with pictilisib, ipatasertib, and rapamycin, selective inhibitors for PI3K, AKT, and mTOR, respectively, resulted in enhanced cancer cell death and reduction of mammosphere numbers in SUM159 cells
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in-vitro, |
Colon, |
CT26 |
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in-vivo, |
NA, |
NA |
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selectivity↑, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy
ChemoSen↑, STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models.
BG↓, glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect
AminoA↓,
Warburg↓,
OCR↑, characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis.
ATP↓,
ROS↑, a significant increase in O2consumption rate (OCR), indicative of an increased oxidative metabolism, was observed
Apoptosis↑,
GlucoseCon↓, STS was as effective as oxaliplatin (OXP) in reducing the average tumor glucose consumption
PI3K↓, STS and in particular STS+OXP down-regulated the expression of PI3K
PTEN↑, and up-regulated PTEN expression
GLUT1↓, STS induced a profound reduction in GLUT1 , GLUT2 , HKII , PFK1, PK
GLUT2↓,
HK2↓,
PFK1↓,
PKA↓,
ATP:AMP↓, Accordingly, the ATP/AMP ratio, a good indicator of cellular energy charge, was dramatically reduced by the two STS settings
Glycolysis↓, results strongly support the effect of STS on reducing glycolysis and lactate production and increasing respiration at Complexes I-IV resulting in superoxide production/oxidative stress but in reduced ATP generation.
lactateProd↓,
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in-vitro, |
PC, |
MIA PaCa-2 |
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in-vitro, |
Nor, |
HPNE |
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in-vitro, |
PC, |
PANC1 |
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in-vivo, |
NA, |
NA |
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TumCG↓, EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner
eff↑, and the growth inhibition effect was further enhanced under glucose deprivation conditions.
ROS↑, EGCG at 40 µM increased ROS levels by 1.4- and 1.6-fold in Panc-1 and MIA PaCa-2 cells, respectively
ECAR↓, EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase.
ChemoSen↑, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo.
selectivity↑, EGCG at 80 µM for 72 h had significantly less effect on the HPNE cells, reducing cell growth by only 24%
Glycolysis↓, EGCG Inhibits Glycolysis through Suppressing Rate-Limiting Enzymes. EGCG Plus Gemcitabine Further Inhibits Glycolysis
PFK↓, EGCG treatment reduced both the activity and expression levels of phosphofructokinase (PFK) and pyruvate kinase (PK) in Panc-1 and MIA PaCa-2 cells
PKA↓,
HK2∅, EGCG failed to reduce hexokinases II (HK2) and lactate dehydrogenase A (LDHA) protein expression levels
LDHA∅,
PFKP↓, EGCG reduced the levels of PFKP and PKM2 (p < 0.01 for both) in pancreatic tumor xenograft homogenates, obtained from mice treated with EGCG
PKM2↓,
H2O2↑, EGCG at 40 µM increased H2O2 levels by 1.5- and 1.9-fold in Panc-1 and MIA PaCa-2 cells
TumW↓, EGCG and gemcitabine, given as single agents, reduced tumor weight by 40% and 52%, respectively, compared to vehicle-treated controls (p < 0.05 and p < 0.01). In combination, EGCG plus gemcitabine reduced tumor weight by 67%,
TumCP↓, We found that PTS can inhibit the proliferation, colony formation, and migration of ESCC cells
TumCMig↓,
PKA↓, PTS can inhibit the PK activity, glucose consumption, and lactate production in ESCC cells.
GlucoseCon↓,
lactateProd↓,
PKM2↓, PTS inhibited the PKM2/STAT3/c-MYC signaling pathway by targeting PKM2 in ESCC cells
STAT3↓,
cMyc↓,
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Review, |
Oral, |
NA |
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Review, |
AD, |
NA |
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α-SMA↓, In oral cancer cells, quercetin could inhibit EMT via up-regulation of claudin-1 and E-cadherin and down-regulation of α-SMA, vimentin, fibronectin, and Slug [29]
α-SMA↑, OSC20 Invasion: ↓Migration, ↑Expression of epithelial markers (E-cadherin & claudin-1), ↑Expression of mesenchymal markers (fibronectin, vimentin, & α-SMA),
TumCP↓, quercetin significantly reduced cancer cell proliferation, cell viability, tumor volume, invasion, metastasis and migration
tumCV↓,
TumVol↓,
TumCI↓,
TumMeta↓,
TumCMig↓,
ROS↑, This anti-cancer agent induced oxidative stress and apoptosis in the cancer cells.
Apoptosis↑,
BioAv↓, The efficacy of quercetin (as lipophilic) is much impacted by its poor absorption rates, which define its bioavailability. The research on quercetin's bioavailability in animal models shows it may be as low as 10%
*neuroP↑, quercetin has been observed to exhibit neuroprotective effects in Alzheimer's disease through its anti-oxidants, and anti-inflammatory properties and inhibition of amyloid-β (Aβ) fibril formation
*antiOx↑,
*Inflam↓,
*Aβ↓,
*cardioP↑, Additionally, quercetin protects the heart by stopping oxidative stress, inflammation, apoptosis, and protein kinases
MMP↓, ↓MMP, ↑Cytosolic Cyt. C,
Cyt‑c↑,
MMP2↓, ↓Activation MMP-2 & MMP-9, ↓Expression levels of EMT inducers & MMPs, Downregulated Twist & Slug
MMP9↓,
EMT↓,
MMPs↓,
Twist↓,
Slug↓,
Ca+2↑, ↑Apoptosis, ↑ROS, ↑Ca2+ production, ↑Activities of caspase‑3, caspase‑8 & caspase‑9
AIF↑, ↑Mitochondrial release of Cyt. C, AIF, & Endo G
Endon↑,
P-gp↓, ↓ Protein levels of P-gp, & P-gp Expression
LDH↑, ↑LDH release
HK2↓, CAL27 cells) 80µM/24h Molecular markers: ↓Activities of HK, PK, & LDH, ↓Glycolysis, ↓Glucose uptake, ↓Lactate production, ↓Viability, ↓G3BP1, & YWHA2 protein levels
PKA↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
GRP78/BiP↑, Quercetin controls the activation of intracellular Ca2+ and calpain-1, which then activates GRP78, caspase-12, and C/EBP homologous protein (CHOP) in oral cancer cells
Casp12↑,
CHOP↑,
AR↓, Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells.
Bcl-xL↓,
TumCP↓,
Glycolysis↓, Sulforaphane at 10 µM reduced the glycolysis and glycolytic capacity by 42% and 39%,
HK2↓, These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells.
PKA↓,
Hif1a↓, Sulforaphane and Capsaicin Reduced the Increased HIF-1α Levels Induced by Androgen Stimulus and Tip60 Overexpression
PSA↓, Sulforaphane and capsaicin prevented the activation of AR signaling (decreased nuclear AR levels and PSA levels)
ECAR↓, and glycolysis (decreased EACR; and HK and PK activities) induced by androgen and Tip60.
BioAv↑, increased sulforaphane bioavailability can be attained after the intake of sulforaphane-enriched broccoli sprout preparation (generated by quick steaming followed by myrosinase treatment) in mice
BioAv↓, Liposomal and methoxypoly (ethylene glycol)-poly(ε-caprolactone) microencapsulation increase capsaicin bioavailability by 3.34-fold and 6-fold respectively in rats
*toxicity↓, considering that the minimum lethal oral dose of capsaicin is 100 mg/Kg body weight in mice, its consumption could be safely increased
Inflam↓, anti-inflammatory effect of UA was linked to attenuation of production of proinflammatory cytokines including tumor necrosis factor α, interleukin (IL)-6 and/or IL-17 (
TNF-α↓,
IL6↓,
IL17↓,
NF-kB↓, UA was associated with suppression of the nuclear factor-κB (NF-κβ) pathway, inhibition of expression of cyclooxygenase-2 (COX-2)
COX2↓,
*AntiDiabetic↑, UA demonstrated an antidiabetic functio
*hepatoP↑, UA can provide hepatoprotective activity against several liver diseases
ALAT↓, UA reduced the serum/plasma levels of alanine transaminase and aspartate transaminase, which are liver disease biomarkers
AST↓,
TumCP↓, UA inhibited tumorigenesis and cancer cell proliferation, modulated apoptosis and cell cycle progression and promoted autophagy
Apoptosis↑,
TumCCA↑,
TumAuto↑,
tumCV↓, UA inhibited the viability and migration of T47D, MCF-7 and MDA-MB-231 breast cancer cells by targeting phosphoinositide-3-kinase/protein kinase B (PI3K/Akt)
TumCMig↓,
Glycolysis↓, Additionally, UA affected glycolysis. The effect was accompanied by decreased levels of ATP, lactate, hexokinase 2 and pyruvate kinase. I
ATP↓,
lactateProd↓,
HK2↓, The Akt inhibition affected glycolysis and markedly decreased levels of HK2, pyruvate kinase M2, ATP and lactate.
PKA↓,
COX2↓, UA may down-regulate the expression of COX-2
mtDam↑, UA significantly enhanced proapoptotic effects and stimulated mitochondrial dysfunction by activating caspases 3, 8 and 9, and downregulated Bcl-2 expression in these cancer cells.
Casp3↑,
Casp8↑,
Casp9↑,
Akt↓, UA downregulated the Akt signaling in three breast cancer cell lines
ROS↑, Derivative 17 significantly increased the production of ROS for 24 h, while 5 and 23 did so for 48 h.
MMP↓, human breast cancer cell line MDA-MB-231, UA decreased the mitochondrial ∆Ψm,
P53↑, regulatory proteins p53 and Bax were upregulated while the antiapoptotic protein Bcl-2 was downregulated following treatment with UA.
Showing Research Papers: 1 to 7 of 7
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
H2O2↑, 1, hyperG↓, 1, ROS↑, 5,
Metal & Cofactor Biology ⓘ
KLF5↓, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 2, MMP↓, 2, mtDam↑, 1, OCR↑, 1,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AminoA↓, 1, ATP:AMP↓, 1, cMyc↓, 1, ECAR↓, 2, GlucoseCon↓, 3, GLUT2↓, 1, Glycolysis↓, 5, HK2↓, 4, HK2∅, 1, lactateProd↓, 4, LDH↑, 1, LDHA∅, 1, PFK↓, 1, PFK1↓, 1, PFKP↓, 1, PKM2↓, 2, Warburg↓, 1,
Cell Death ⓘ
Akt↓, 1, Akt↑, 2, Apoptosis↑, 3, ASK1↑, 1, Bcl-xL↓, 1, BIM↑, 1, Casp12↑, 1, Casp3↑, 2, Casp8↑, 1, Casp9↑, 1, Cyt‑c↑, 1, Endon↑, 1,
Transcription & Epigenetics ⓘ
tumCV↓, 2,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, GRP78/BiP↑, 1,
Autophagy & Lysosomes ⓘ
TumAuto↑, 1,
DNA Damage & Repair ⓘ
P53↑, 1,
Cell Cycle & Senescence ⓘ
CDK1↓, 1, CDK4↑, 2, TumCCA↑, 1,
Proliferation, Differentiation & Cell State ⓘ
EMT↓, 1, p‑GSK‐3β↑, 1, mTOR↑, 2, Nanog↓, 1, OCT4↓, 1, PI3K↓, 1, PI3K↑, 2, PTEN↑, 1, STAT3↓, 1, TumCG↓, 2,
Migration ⓘ
Ca+2↑, 1, KLF2↓, 1, MMP2↓, 1, MMP9↓, 1, MMPs↓, 1, PKA↓, 7, Slug↓, 1, TumCI↓, 1, TumCMig↓, 3, TumCP↓, 4, TumMeta↓, 1, Twist↓, 1, α-SMA↓, 1, α-SMA↑, 1,
Angiogenesis & Vasculature ⓘ
Hif1a↓, 1,
Barriers & Transport ⓘ
GLUT1↓, 1, P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 2, IL17↓, 1, IL6↓, 1, Inflam↓, 1, NF-kB↓, 1, PSA↓, 1, TNF-α↓, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1, CDK6↑, 2,
Drug Metabolism & Resistance ⓘ
BioAv↓, 2, BioAv↑, 1, ChemoSen↑, 2, eff↑, 4, eff∅, 1, selectivity↑, 2,
Clinical Biomarkers ⓘ
ALAT↓, 1, AR↓, 1, AST↓, 1, BG↓, 2, IL6↓, 1, LDH↑, 1, PSA↓, 1,
Functional Outcomes ⓘ
TumVol↓, 2, TumW↓, 1,
Total Targets: 98
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 1,
Immune & Inflammatory Signaling ⓘ
Inflam↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Functional Outcomes ⓘ
AntiDiabetic↑, 1, cardioP↑, 1, hepatoP↑, 1, neuroP↑, 1, toxicity↓, 1,
Total Targets: 8
Scientific Paper Hit Count for: PKA, protein kinase A
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
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