cal2 Cancer Research Results

cal2, calpain-2: Click to Expand ⟱
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Calpain-2 is a calcium-dependent cysteine protease that plays important roles in a variety of cellular processes, including migration, adhesion, signal transduction, and apoptosis.
In many cancer types, Calpain-2 is found to be upregulated. Elevated levels of Calpain-2 have been associated with enhanced proteolytic activity, which can contribute to cancer progression by facilitating processes such as cell migration, invasion, and metastasis.
• The increased expression of Calpain-2 in cancer cells can promote the degradation of cytoskeletal and adhesion proteins, thereby aiding in tumor cell detachment and dissemination. This is particularly relevant during epithelial-to-mesenchymal transition (EMT) and remodeling of the extracellular matrix.
• Calpain-2 activity, which is regulated by intracellular Ca²⁺ levels and calpastatin (its endogenous inhibitor), may also influence signal transduction pathways that are critical for cell proliferation and survival. Alterations in these regulatory mechanisms in a tumor setting can amplify Calpain-2’s impact.

Calpain-2 is commonly upregulated in many cancer types, and this increased expression is thought to promote tumor progression by enhancing cellular invasiveness, migration, and survival through its proteolytic actions.
Scientific Papers found: Click to Expand⟱
1301- Api,    Bcl-2 inhibitor and apigenin worked synergistically in human malignant neuroblastoma cell lines and increased apoptosis with activation of extrinsic and intrinsic pathways
- in-vitro, neuroblastoma, NA
BAX↑,
Bcl-2↓,
Cyt‑c↑, release of cytochrome c into the cytosol
cal2↑,
Casp3↑,

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

5852- CAP,    Capsaicin Synergizes with Camptothecin to Induce Increased Apoptosis in Human Small Cell Lung Cancers via the Calpain Pathway
- vitro+vivo, NSCLC, NA
ChemoSen↑, Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models
Ca+2↑, The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway.
cal2↑,

5052- HPT,    Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells
- in-vitro, OS, U2OS
Apoptosis↑, Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells.
ROS↑, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells.
Casp3↑,
mtDam↑, Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax.
Cyt‑c↑,
Bcl-2↓,
Bcl-xL↓,
Bak↑,
BAX↓,
ER Stress↑, Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity.
Ca+2↝,
cal2↑,

5126- Sal,    Salinomycin induces calpain and cytochrome c-mediated neuronal cell death
CSCs↓, highly effective in the elimination of cancer stem cells (CSCs) both in vitro and in vivo.
Ca+2↑, This toxic effect is mediated by elevated cytosolic Na+ concentrations, which in turn cause an increase of cytosolic Ca2+ by means of Na+/Ca2+ exchangers (NCXs)
cal2↑, Elevated Ca2+ then leads to calpain activation, which triggers caspase-dependent apoptosis involving caspases 12, 9 and 3.
Casp12↑,
Casp9↑,
Casp3↑,
Cyt‑c↑, In addition, cytochrome c released from depolarized mitochondria directly activates caspase 9
MMP↓,

1735- SFN,    Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane
- in-vitro, GBM, T98G - in-vitro, GBM, U87MG
Apoptosis↑, confirmed apoptosis in glioblastoma cells treated with sulforaphane
Ca+2↑, Increase in intracellular free Ca2+ was detected by fura-2 assay, suggesting activation of Ca2+-dependent pathways for apoptosis.
Bax:Bcl2↑, increased Bax:Bcl-2 ratio
cal2↑, Upregulation of calpain, a Ca2+-dependent cysteine protease, activated caspase-12 that in turn caused activation of caspase-9.
Casp12↑,
Casp9↑,
Cyt‑c↑, cytochrome c was released from mitochondria to cytosol


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 1,  

Cell Death ⓘ

Akt↓, 1,   APAF1↑, 1,   Apoptosis↑, 2,   Bak↑, 1,   BAX↓, 1,   BAX↑, 1,   Bax:Bcl2↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp↑, 1,   Casp12↑, 2,   Casp3↑, 3,   cl‑Casp3↑, 1,   cl‑Casp7↑, 1,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   CK2↓, 2,   Cyt‑c↑, 6,   cl‑IAP2↑, 1,   p‑JNK↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

p‑pRB↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   HSPs↓, 1,  

DNA Damage & Repair ⓘ

P53↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK4↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   ERK↓, 1,   p‑GSK‐3β↓, 1,   IGF-1↓, 1,   IGFBP3↑, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↑, 4,   Ca+2↝, 1,   cal2↑, 6,   E-cadherin↑, 1,   FAK↓, 1,   ITGB4↓, 1,   MMPs↓, 1,   TumCI↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   HER2/EBBR2↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 64

Pathway results for Effect on Normal Cells:


Cell Death ⓘ

MAPK↓, 1,  

Migration ⓘ

PKCδ↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 3

Scientific Paper Hit Count for: cal2, calpain-2
2 Apigenin (mainly Parsley)
1 Capsaicin
1 Hyperthermia
1 salinomycin
1 Sulforaphane (mainly Broccoli)
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#:1000  State#:%  Dir#:2
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