Ca+2 Cancer Research Results

Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
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.
Stroke, Cerebral Ischemic Stroke: Click to Expand ⟱
Ischemic stroke is also called brain ischemia and cerebral ischemia. Ischemia is the medical term for "lack of blood supply."

Quick Reference

Mechanism Top Compounds
Blood flow / anti-thrombotic support Aspirin, Ginkgo biloba, Panax notoginseng, Salvia miltiorrhiza
Membrane repair / cholinergic support Citicoline, Alpha-GPC
Antioxidant / ROS control EGCG, Curcumin, Quercetin, Tocotrienols
Anti-inflammatory / NF-κB / cytokines Curcumin, Luteolin, Baicalin
Mitochondrial protection Resveratrol, Citicoline
BBB protection Rosmarinic acid, Astragaloside IV

Stroke/Product Table - Dose + Practical Therapeutic Index

Compound Class Primary Mechanisms Key Stroke Effects Evidence Level Phase Utility Human Dose Range Approx. HED mg/kg/day Practical Therapeutic Index
Aspirin NSAID / anti-platelet COX-1 inhibition; ↓ thromboxane A2; ↓ platelet aggregation Reduces recurrent ischemic stroke risk Strong clinical; standard of care Acute + prevention 81–325 mg/day ~1.2–4.6 mg/kg/day for 70 kg adult High, but bleeding-risk limited
Citicoline / CDP-choline Choline donor Membrane repair; ↑ phosphatidylcholine; ↓ free fatty acid release May support neurological and cognitive recovery Clinical; mixed acute results, better recovery/cognition signal Recovery 500–2000 mg/day ~7–29 mg/kg/day for 70 kg adult Moderate–High
Alpha-GPC Choline donor ↑ acetylcholine; phospholipid support May support post-stroke cognition Clinical; moderate support Recovery 300–1200 mg/day ~4–17 mg/kg/day for 70 kg adult Moderate; TMAO concern
Ginkgo biloba Herbal extract Cerebral blood flow; antioxidant; anti-platelet May support perfusion and cognition Clinical + preclinical Recovery 120–240 mg/day standardized extract ~1.7–3.4 mg/kg/day Moderate; bleeding interaction caution
Panax notoginseng / PNS Saponins Anti-thrombotic; perfusion; anti-inflammatory Improved blood flow/recovery measures in some studies Clinical mainly China + preclinical Acute + recovery Variable extract-dependent Study-specific; often preclinical HED needed Moderate; bleeding interaction caution
Salvia miltiorrhiza / Danshen Herbal extract Microcirculation; vascular protection; anti-platelet May support vascular recovery Clinical mainly China + preclinical Acute + recovery Variable extract/root equivalent Study-specific Moderate; bleeding interaction caution
Baicalin Flavonoid Anti-inflammatory; anti-apoptotic; antioxidant Neuroprotection in ischemic injury models Preclinical + limited clinical Acute No established stroke dose Preclinical HED only Moderate–Low
Curcumin Polyphenol ↓ NF-κB; ↓ cytokines; antioxidant Reduced infarct size/inflammation in models Strong preclinical Acute + recovery 500–2000 mg/day bioavailable form ~7–29 mg/kg/day Moderate; bioavailability limited
Resveratrol Polyphenol SIRT1; mitochondrial protection; anti-apoptotic Reduced apoptosis/infarct injury in models Strong preclinical Acute + recovery 100–500 mg/day ~1.4–7.1 mg/kg/day Moderate; bioavailability limited
EGCG Catechin ROS scavenging; vascular protection Reduced neuronal injury in models Strong preclinical Acute 200–400 mg/day EGCG ~2.9–5.7 mg/kg/day Moderate; liver-dose caution
Quercetin Flavonoid Antioxidant; anti-inflammatory; anti-edema Reduced edema/infarct size in models Strong preclinical Acute 500–1000 mg/day ~7–14 mg/kg/day Moderate
Melatonin Indoleamine Mitochondrial antioxidant; anti-inflammatory Reduced ischemia-reperfusion injury in models Preclinical + limited clinical interest Acute + recovery 3–10 mg/day ~0.04–0.14 mg/kg/day Moderate–High
Tocotrienols Vitamin E subtype Lipid antioxidant; membrane protection Neuroprotection in ischemic models Preclinical + limited clinical Acute 100–300 mg/day ~1.4–4.3 mg/kg/day Moderate
Luteolin Flavonoid NF-κB / Nrf2 / PI3K-Akt modulation Reduced inflammation/neuroprotection in models Strong preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Ferulic acid Phenolic acid Antioxidant; vasodilation; vascular protection Improved blood flow/reduced injury in models Preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Rosmarinic acid Phenolic acid BBB protection; antioxidant; anti-inflammatory Reduced BBB disruption in models Preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Berberine Alkaloid AMPK activation; metabolic/vascular protection Neuroprotection in ischemia models Preclinical Prevention + recovery 500–1500 mg/day ~7–21 mg/kg/day Moderate; interaction caution
Huperzine A Alkaloid AChE inhibition; cholinergic support May support cognitive recovery Preclinical + cognitive clinical context Recovery 100–200 µg/day ~0.001–0.003 mg/kg/day Low–Moderate; narrow cholinergic tolerance
Honokiol Lignan Mitochondrial protection; anti-inflammatory Reduced ischemic neuronal injury in models Preclinical Acute + recovery No established stroke dose Preclinical HED only Low
HED: Human Equilvalent Dose
Scientific Papers found: Click to Expand⟱
2782- CHr,    Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives
- Review, Var, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, *Inflam↓, *hepatoP↑, *neuroP↑, *BioAv↓, *cardioP↑, *lipidLev↓, *RenoP↑, *TNF-α↓, *IL2↓, *PI3K↓, *Akt↓, *ROS↓, *cognitive↑, eff↑, cycD1/CCND1↓, hTERT/TERT↓, VEGF↓, p‑STAT3↓, TumMeta↓, TumCP↓, eff↑, eff↑, IL1β↓, IL6↓, NF-kB↓, ROS↑, MMP↓, Cyt‑c↑, Apoptosis↑, ER Stress↑, Ca+2↑, TET1↑, Let-7↑, Twist↓, EMT↓, TumCCA↑, Casp3↑, Casp9↑, BAX↑, HK2↓, GlucoseCon↓, lactateProd↓, Glycolysis↓, SHP1↑, N-cadherin↓, E-cadherin↑, UPR↑, PERK↑, ATF4↑, eIF2α↑, RadioS↑, NOTCH1↑, NRF2↓, BioAv↑, eff↑,
5904- TV,    Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development
- Review, Var, NA - Review, Stroke, NA - Review, Diabetic, NA - Review, Obesity, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, *ROS↓, *Inflam↓, *Bacteria↓, AntiTum↑, IronCh↑, *HDL↑, *LDL↓, *BioAv↝, *Half-Life↝, *BioAv↑, *SOD↑, *GPx↑, *GSTs↑, *eff↑, radioP↑, *MDA↓, *other↑, *COX1↓, *COX2↓, *AntiAg↑, *RNS↓, *NO↓, *H2O2↓, *NOS2↓, *NADH↓, *Imm↑, Apoptosis↑, TumCP↓, angioG↓, TumCMig↓, Ca+2↑, TumCCA↑, DNAdam↑, BAX↑, Casp9↑, Casp8↑, Casp3↑, cl‑PARP↑, AIF↑, i-ROS↑, MMP↓, Cyt‑c↑, APAF1↑, Ca+2↑, MMP9↓, MMP2↓, PKCδ↓, ERK↓, H2O2↑, BAX↑, Bcl-2↓, DNAdam↑, lipid-P↑, ChemoSen↑, chemoP↑, *cardioP↑, *SOD↑, *Catalase↑, *GPx↑, *GSH↑, *BP↓, *AntiDiabetic↑, *Obesity↓, RenoP↑, *GastroP↑, hepatoP↑, *AChE↓, *cognitive↑, *BChE↓, *other↓, *BioAv↑,

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 ⓘ

H2O2↑, 1,   lipid-P↑, 1,   NRF2↓, 1,   ROS↑, 1,   i-ROS↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,  

Cell Death ⓘ

APAF1↑, 1,   Apoptosis↑, 2,   BAX↑, 3,   Bcl-2↓, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 2,   hTERT/TERT↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 1,   ER Stress↑, 1,   PERK↑, 1,   UPR↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   Let-7↑, 1,   NOTCH1↑, 1,   SHP1↑, 1,   p‑STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 3,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   PKCδ↓, 1,   TET1↑, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   eff↑, 4,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   radioP↑, 1,   RenoP↑, 1,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 2,   GSH↑, 1,   GSTs↑, 1,   H2O2↓, 1,   HDL↑, 1,   MDA↓, 1,   NADH↓, 1,   RNS↓, 1,   ROS↓, 2,   SOD↑, 2,  

Core Metabolism/Glycolysis ⓘ

LDL↓, 1,   lipidLev↓, 1,  

Cell Death ⓘ

Akt↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,   other↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Migration ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

GastroP↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 1,   IL2↓, 1,   Imm↑, 1,   Inflam↓, 2,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   eff↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   NOS2↓, 1,  

Functional Outcomes ⓘ

AntiDiabetic↑, 1,   cardioP↑, 2,   cognitive↑, 2,   hepatoP↑, 1,   neuroP↑, 1,   Obesity↓, 1,   RenoP↑, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 44

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
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:36  Cells:%  prod#:%  Target#:38  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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