CaMKII Cancer Research Results

CaMKII , Calcium/Calmodulin-dependent Protein Kinase II: Click to Expand ⟱

Source:

Type:

CaMKII, short for Calcium/Calmodulin-dependent Protein Kinase II, is not a single protein but rather a family of related enzymes composed of several isoforms.
Breakdown:
CaMKII Isoforms:4 genes encoding the major isoforms: α(alpha), β(beta), γ(gamma), and δ(delta). CaMKIIα and CaMKIIβ are abundant in neuronal tissue, while CaMKIIδ is more prevalent in the heart and other non-neuronal tissues.

-Overexpression or hyperactivation of CaMKII has been linked in some studies to enhanced cell cycle progression and resistance to apoptosis, both of which are features of more aggressive tumors.
-In some cancers, upregulation or increased activity of CaMKII has been associated with poor clinical outcomes, including lower overall survival or higher recurrence rates.

Scientific Papers found: Click to Expand⟱

5536-

BBM,

Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers

Review,

Var,

JAK↝, In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers.
STAT3↓, Berbamine physically interacted with STAT3 and inhibited its activation [8].
p‑CaMKII ↓, An orally administered, bioactive small molecule analog of berbamine, tosyl chloride-berbamine (TCB), considerably reduced phosphorylated levels of CaMKIIγ
TGF-β↑, berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression.
Smad1↑,
ChemoSen↑, Berbamine enhanced the chemosensitivity of gefitinib against PANC-1 and MIA PaCa-2 cancer cells [8].
RadioS↑, Moreover, berbamine and radiation effectively induced a regression of the tumors in mice subcutaneously injected with FaDu cells [10].
TumCI↓, berbamine-GMO-TPGS nanoparticles showed superior cellular toxicity, as well as an inhibition of migration and invasion in metastatic breast cancer MDA-MB-231,
TumCMig↓,
ROS↑, Berbamine increased the intracellular ROS levels via the downregulation of antioxidative genes such as NRF2, SOD2, GPX-1 and HO-1.
NRF2↓,
SOD2↓,
GPx1↓,
HO-1↓,

5537-

BBM,

CaMKII γ, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine

in-vitro,

CLL,

CaMKII ↓, Berbamine specifically binds to the ATP-binding pocket of CaMKII γ, inhibits its phosphorylation and triggers apoptosis of leukemia cells.
NF-kB↓, Berbamine analogs inhibit NF-κB signaling pathways,
IKKα↓, berbamine treatment significantly down-regulated IKKα, a downstream target of CaMKII γ
p‑STAT3↓, Similarly, berbamine also potently inhibited phosphorylation of Stat3 of CML cells

5538-

BBM,

Stabilization of the c-Myc protein by CAMKIIγ promotes T cell lymphoma

Review,

lymphoma,

CaMKII ↓, Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden.
cMyc↝,

5542-

BBM,

Pharmacological profiling of a berbamine derivative for lymphoma treatment

vitro+vivo,

lymphoma,

CaMKII ↓, PA4 is a potent CAMKIIγ inhibitor.
TumCG↓, PA4 significantly impeded tumor growth in vivo in a xenograft T-cell lymphoma mouse model.
cMyc↓, PA4 reduced c-Myc levels and induced ROS in lymphoma cells
ROS↑,
UPR↑, Unfolded protein response (UPR) was elevated after PA4 treatment
ER Stress↑, UPR induces ER stress
PERK↑, PA4 treatment significantly increased protein kinase RNA-like ER kinase (PERK)
BioAv↑, Both BBM and PA4 were rapidly absorbed into the blood and detected 5 minutes after oral administration.
toxicity↓, mice received oral gavage with 50 mg/kg PA4 daily for 12 consecutive days (n = 6). After 12 days, there were no mortalities and no significant reductions in body weight (Figure 7D). Serum alanine aminotransferase and aspartate aminotransferase levels

5546-

BBM,

Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca²⁺/calmodulin-dependent protein kinase II

vitro+vivo,

Liver,

TumCP↓, berbamine (BBM) and one of its derivatives, bbd24, potently suppressed liver cancer cell proliferation and induced cancer cell death by targeting Ca2+/calmodulin-dependent protein kinase II (CAMKII).
CaMKII ↓,

5549-

BBM,

Synergistic Anticancer Effect of a Combination of Berbamine and Arcyriaflavin A against Glioblastoma Stem-like Cells

in-vitro,

GBM,

eff?, Combined treatment with berbamine and ArcA synergistically inhibited cell viability and tumorsphere formation in U87MG- and C6-drived GSCs.
tumCV↓,
TumCG↓, both compounds potently inhibited tumor growth in a U87MG GSC-grafted chick embryo chorioallantoic membrane (CAM) model.
ROS↑, anticancer effect of berbamine and ArcA on GSC growth is associated with the promotion of reactive oxygen species (ROS)- and calcium-dependent apoptosis
P53↑, ia strong activation of the p53-mediated caspase cascade.
CSCs↓, co-treatment with both compounds significantly reduced the expression levels of key GSC markers, including CD133, integrin α6, aldehyde dehydrogenase 1A1 (ALDH1A1), Nanog, Sox2, and Oct4.
CD133↓,
ALDH1A1↓,
Nanog↓,
SOX2↓,
OCT4↓,
CDK1↓, downregulation of cell cycle regulatory proteins, such as cyclins and CDKs, by potent inactivation of the CaMKIIγ-mediated STAT3/AKT/ERK1/2 signaling pathway.
CaMKII ↓,
STAT3↓,
Akt↓,
ERK↓,

5553-

BBM,

A review on berbamine–a potential anticancer drug

Review,

Var,

P-gp↓, Treatment with berbamine decreased P-glycoprotein (P-gp) expression and down-regulated expression of MDR1 (multi-drug resistance1) and survivin mRNA in K562/A02 cells
MDR1↓,
survivin↓,
NF-kB↓, decrease expression of nuclear factor-B (NF-B), phosphoIB, IKK, and survivin.
TumCP↓, In a chronic myeloid leukemia cell line KU812, berbamine inhibited cell proliferation in a time- and dose-dependent manner, with IC50 values for treatments of 24, 48, and 72 h at 5.83, 3.43, and 0.75 μg/ml, respectively.
TumCCA↑, Berbamine induced cell cycle arrest at the G1 phase and also induced apoptosis.
Apoptosis↑,
SMAD3↑, The compound up-regulated transcriptions of Smad3 and p21, and increased protein levels of both total Smad3 and phosphorylated Smad3.
P21↑,
cycD1/CCND1↓, The protein levels of cyclin D1 and c-Myc were reduced.
cMyc↑,
Bcl-2↓, The levels of the anti-apoptotic proteins Bcl-2 and Bcl-xL were decreased, and the level of the pro-apoptotic protein Bax was increased.
Bcl-xL↓,
BAX↑,
CaMKII ↓, The compound has been shown to specifically bind to the ATP-binding pocket of calmodulin kinase (CAMK)II, inhibit its phosphorylation, and trigger apoptosis.
ChemoSen↑, Berbamine also significantly enhanced the activity of anticancer drugs like trichostatin A and celecoxib.
MMP2↓, EBB down-regulated the activities and mRNA levels of matrix metalloproteinases (MMP) 2 and 9, and up-regulated the mRNA levels of tissue inhibitor of metalloproteinases (TIMP) 1.
MMP9↓,
TIMP1↑,
cl‑Casp3↑, induction of apoptosis, including activation and cleavage of caspases 3, 8, 9 and PARP.
cl‑Casp9↑,
cl‑Casp8↑,
cl‑PARP↑,
IL6↓, BBD inhibited autocrine IL-6 production, and down-regulated membrane IL-6 receptor (IL-6R) expression.
ROS↑, Production of reactive oxygen species (ROS) was increased by BBMD3 in these cells.

1585-

Citrate,

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer

in-vitro,

Ovarian,

SKOV3

15.93 mM

in-vitro,

Ovarian,

A2780S

16.8 mM

in-vitro,

Nor,

HEK293

Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1580-

Citrate,

Citrate activates autophagic death of prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway

in-vitro,

Pca,

PC3

 (0-3 mM)

in-vivo,

PC,

50 mg/kg/day, i.p.)

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

WPMY-1

 (0-3 mM)

Apoptosis↑,
Ca+2↓, Ca2+-chelating property of citrate
Akt↓, downregulation CaMKII/AKT/mTOR pathway
mTOR↓,
selectivity↑, citrate (0-3 mM) did not affect the cell growth of normal prostate epithelial cells (WPMY-1).
TumCP↓, also verified that citrate significantly inhibited the proliferation of PCa cells (PC3 and LNCaP).
cl‑Casp3↑,
cl‑PARP↑, increased the levels of Cleaved caspase3 and Cleaved PARP in prostate cancer cells
LC3‑Ⅱ/LC3‑Ⅰ↑, ratio of LC3-II/I was markedly increased and the expression of p62 was significantly decreased after the treatment of citrate in PCa cells (PC3 and LNCaP).
p62↓,
ATG5↑, citrate also promoted the protein expression of Atg5, Atg7 and Beclin-1 in PCa cells (PC3 and LNCaP).
ATG7↑,
Beclin-1↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII ↓, citrate suppresses the activation of the CaMKI

4289-

RES,

Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells

in-vitro,

AD,

0.1–10 μM

 N2a cells

*antiOx↑, Resveratrol (Res), as a polyphenol anti-oxidant, has been considered to have therapeutic potential for the treatment of AD.
*p‑tau↓, Res significantly decreased FA-induced cytotoxicity, reduced cell apoptosis rates, and inhibited the hyperphosphorylation of tau protein at Thr181 in a dose-dependent manner.
*GSK‐3β↓, Further tests revealed that this effect was associated with the suppression of glycogen synthase kinase (GSK-3β)
*CaMKII ↓, and calmodulin-dependent protein kinase II (CaMKII) activities, both of which are important kinases for tau protein hyperphosphorylation.
*PP2A↑, Res was found to increase the activity of phosphoseryl/phosphothreonyl protein phosphatase-2A (PP2A).
*neuroP↑, Neuroprotective effects of Res against FA-induced cytotoxicity

3025-

RosA,

Rosmarinic acid alleviates intestinal inflammatory damage and inhibits endoplasmic reticulum stress and smooth muscle contraction abnormalities in intestinal tissues by regulating gut microbiota

in-vivo,

IBD,

*GutMicro↑, RA upregulated the abundance of Lactobacillus johnsonii and Candidatus Arthromitus sp SFB-mouse-NL and downregulated the abundance of Bifidobacterium pseudolongum, Escherichia coli, and Romboutsia ilealis.
*ROCK1↓, RA downregulated the expressions of ROCK, RhoA, CaM, MLC, MLCK, ZEB1, ZO-1, ZO-2, occludin, E-cadherin, IL-1β, IL-6, TNF-α, GRP78, PERK, IRE1, ATF6, CHOP, Caspase12, Caspase9, Caspase3, Bax, Cytc, RIPK1, RIPK3, MLKL
*Rho↓,
*CaMKII ↓,
*Zeb1↓,
*ZO-1↓,
*E-cadherin↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*GRP78/BiP↓,
*PERK↓,
*IRE1↓,
*ATF6↓,
*CHOP↓,
*Casp12↓,
*Casp9↓,
*BAX↓,
*Casp3↓,
*Cyt‑c↓,
*RIP1↓,
*MLKL↓,
*IL10↑, upregulated the expression of IL-10 and Bcl-2.
*Bcl-2↑,
*ER Stress↓, RA inhibited the inflammation, which is caused by tight junction damage, by repairing intestinal flora dysbiosis, relieved endoplasmic reticulum stress, inhibited cell death

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

toxicity↓, 1,
Total Targets: 96

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1,

Cell Death ⓘ

BAX↓, 1, Bcl-2↑, 1, Casp12↓, 1, Casp3↓, 1, Casp9↓, 1, Cyt‑c↓, 1, MLKL↓, 1, RIP1↓, 1,

Kinase & Signal Transduction ⓘ

CaMKII ↓, 2,

Protein Folding & ER Stress ⓘ

ATF6↓, 1, CHOP↓, 1, ER Stress↓, 1, GRP78/BiP↓, 1, IRE1↓, 1, PERK↓, 1,

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,

Migration ⓘ

E-cadherin↓, 1, Rho↓, 1, ROCK1↓, 1, Zeb1↓, 1, ZO-1↓, 1,

Immune & Inflammatory Signaling ⓘ

IL10↑, 1, IL1β↓, 1, IL6↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,

Protein Aggregation ⓘ

PP2A↑, 1,

Clinical Biomarkers ⓘ

GutMicro↑, 1, IL6↓, 1,

Functional Outcomes ⓘ

neuroP↑, 1,
Total Targets: 31

Scientific Paper Hit Count for: CaMKII , Calcium/Calmodulin-dependent Protein Kinase II

7 Berbamine
2 Citric Acid
1 Resveratrol
1 Rosmarinic acid

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#:1142  State#:%  Dir#:1
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CaMKII Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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