Ca+2 Cancer Research Results

Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
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In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
Scientific Papers found: Click to Expand⟱
3887- Api,    The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice
- in-vivo, AD, NA
*Inflam↓, anti-inflammatory, anticarcinogenic, and free radical-scavenging activities.
*ROS↓,
*Aβ↓, Recent studies revealed its protective effects against amyloid-β (Aβ)-induced neurotoxicity, but the mechanism was unclear. I
*memory↑, involving improvement of the learning and memory capabilities,
*AChE↓, improvement of cholinergic system involving the inhibition of AChE activity and elevation of ACh level, and modification of BNDF, TrkB, and phospho-CREB levels.
*Ach↑,
*Dose↑, Apigenin, at doses of 10 mg/kg and 20 mg/kg, promoted learning and memory
*BDNF↑, apigenin also increased BDNF level and up-regulated its receptor TrkB and pCREB in A25-35 -induced amnesic mice.
*TrkB↑,
*p‑CREB↑,
*BBB↑, Additionally, we found that treatment with apigenin was effective in preserving anatomical and functional integrity of the BBB per- meability.
*Ca+2?, A relevant effect of apigenin by suppressing the Ca 2+ influx through both voltage- and receptor-operated calcium channels might be attributed to the changes of rCBF

3521- Bor,    A new hope for obesity management: Boron inhibits adipogenesis in progenitor cells through the Wnt/β-catenin pathway
- in-vitro, Obesity, 3T3
*CEBPA↓, Figure 2
*PPARγ↓,
*FASN↓,
*SREBP1↓,
*FABP4↓,
*GLUT4↓,
*β-catenin/ZEB1↑, Boron Activated the β-Catenin Signaling Pathway
*MMP2↓, As shown in Fig. 6, soluble transforming growth factor receptor 1 (sTNFR1) and matrix metalloproteinase 2 (MMP2) protein levels decreased in the presence of boron
*FGF↑, whereas basic fibroblast growth factor expression (bFGF) increased
*Ca+2?, Boric acid has been reported to interact with NAD + and inhibit cyclic ADP ribose-activated Ca 2+ release from ryanodine receptor, leading to decreased endoplasmic reticulum luminal Ca 2+ concentrations

2019- CAP,    Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer
- Review, Var, NA
chemoPv↑, Capsaicin has shown significant prospects as an effective chemopreventive agent
Ca+2↑, Capsaicin was shown to cause upstream activation of Ca2+
antiOx↑, Another plausible mechanism implicated in the chemopreventive action of capsaicin is its anti-oxidative effects.
*ROS↓, capsaicin inhibits ROS release and the subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxidized low-density lipoprotein in normal human HUVEC cells
*MMP∅,
*Cyt‑c∅,
*Casp3∅,
*eff↑, dietary curcumin and capsaicin concurrent administration in high-fat diet-fed rats were shown to mitigate the testicular and hepatic antioxidant status by increasing GSH levels, glutathione transferase activity, and Cu-ZnSOD expression
*Inflam↓, Anti-inflammation is another mechanism implicated in the chemopreventive action of capsaicin.
*NF-kB↓, inhibition of NF-kB by capsaicin
*COX2↓, compound elicits COX-2 enzyme activity inhibition and downregulation of iNOS
iNOS↓,
TRPV1↑, major pro-apoptotic mechanisms of capsaicin is via the vanilloid receptors, primarily TRPV1
i-Ca+2?, causing a concomitant influx of Ca2+: severe condition of mitochondria calcium overload. at high concentration (> 10 µM), capsaicin induces a slow but persistent increase in intracellular Ca2+
MMP↓, depolarization of mitochondria membrane potential
Cyt‑c↑, release of cytochrome C
Bax:Bcl2↑, activation of Bax and p53 through C-jun N-terminal kinase (JNK) activation
P53↑,
JNK↑,
PI3K↓, blocking the Pi3/Akt/mTOR signalling pathway, capsaicin increases levels of autophagic markers (LC3-II and Atg5)
Akt↓,
mTOR↓,
LC3II↑,
ATG5↑,
p62↑, enhances p62 and Fap-1 degradation and increases caspase-3 activity to induce apoptosis in human nasopharyngeal carcinoma cells
Fap1↓,
Casp3↑,
Apoptosis↑,
ROS↑, generation of ROS in human hepatoma (HepG2 cells)
MMP9↓, inhibition of MMP9 by capsaicin occurs via the suppression of AMPK-NF-κB, EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling pathway
eff↑, capsaicin 8% patch could promote the regeneration and restoration of skin nerve fibres in chemotherapy-induced peripheral neuropathy in addition to pain relief
eff↓, capsaicin has shown several unpleasant side effects, including stomach cramps, skin and gastric irritation, and burning sensation
eff↑, liposomes and micro-emulsion-based drugs have been known to significantly improve oral bioavailability and reduce the irritation of drugs
selectivity↑, In addition, these delivery systems can be surfaced-modified to perform site-directed/cell-specific drug delivery, thereby ensuring increased cell death of cancer cells while sparing non-selective normal cells
eff↑, Furthermore, owing to its antioxidant potential, capsaicin has been applied as a bioreduction and capping agent to synthesize biocompatible silver nanoparticles
ChemoSen↑, capsaicin has been combined with other anticancer therapies for more pronounced anticancer effects

1579- Citrate,    Effect of Food Additive Citric Acid on The Growth of Human Esophageal Carcinoma Cell Line EC109
- in-vitro, ESCC, Eca109
TumCP↓, higher citric acid concentrations (800, 1600 μg/ml)
e-LDH↑, incubation with either 400, 800 or 1600 µg/ml CA for 48 hours caused a significant increase (P<0.01) in LDH release by 1.67-fold, 2.79fold and 3.16-fold, respectively
MMP↓,
Ca+2?, CA level can directly regulate several metabolic pathways and increase calcium uptake from foods
PFK↓, potential inhibitor of PFK
Glycolysis↓, increasingly evidences have indicated that a high level of citrate could inhibit the glycolytic pathway

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,   lactateProd↓, 1,   e-LDH↑, 1,   PFK↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 2,   BAD↑, 1,   Bak↑, 1,   Bax:Bcl2↑, 1,   Casp3↑, 2,   Casp8↓, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   Fap1↓, 1,   Fas↑, 1,   iNOS↓, 1,   JNK↑, 1,   Myc↓, 1,   TRPV1↑, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 2,   Beclin-1↑, 1,   LC3B↑, 1,   LC3II↑, 2,   p62↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   PARP↑, 1,   TP53↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1R↑, 1,   mTOR↓, 1,   NOTCH3↓, 1,   PI3K↓, 1,   Wnt↑, 1,  

Migration ⓘ

Ca+2?, 1,   Ca+2↑, 1,   i-Ca+2?, 1,   MMP9↓, 1,   TumCP↓, 1,   Zeb1↑, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 1,   VEGF↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 4,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

e-LDH↑, 1,   Myc↓, 1,   TP53↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 57

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   MPO↓, 1,   ROS↓, 3,  

Mitochondria & Bioenergetics ⓘ

MMP∅, 1,  

Core Metabolism/Glycolysis ⓘ

p‑CREB↑, 1,   FABP4↓, 1,   FASN↓, 1,   glucose↓, 1,   LDL↓, 1,   PPARγ↓, 1,   SREBP1↓, 1,  

Cell Death ⓘ

BAX↓, 1,   Casp3∅, 1,   Cyt‑c↓, 1,   Cyt‑c∅, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CEBPA↓, 1,   FGF↑, 1,  

Migration ⓘ

Ca+2?, 3,   MMP2↓, 1,   β-catenin/ZEB1↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT4↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 3,   NF-kB↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose↑, 1,   eff↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   memory↑, 2,   neuroP↑, 1,  
Total Targets: 35

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
1 Apigenin (mainly Parsley)
1 Boron
1 Capsaicin
1 Citric Acid
1 EGCG (Epigallocatechin Gallate)
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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