Casp3 Cancer Research Results

Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
3160- Ash,    Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal
- Review, Var, NA
TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

2020- CAP,    Capsaicinoids and Their Effects on Cancer: The “Double-Edged Sword” Postulate from the Molecular Scale
- Review, Var, NA
AntiTum↑, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer,
selectivity↑, while non-cancer cells tend to have greater tolerance
TRPV1↑, activation or phosphorylation of TRPV1
MMP↓, leads to cell membrane depolarization through the influx of Na2+ and Ca2+,
Ca+2↑,
ER Stress↑, endoplasmic reticulum stress [73], and the inhibition of angiogenesis
angioG↓,
Casp3?, increase in caspase-3 activation, PARP-1 cleavage
cl‑PARP↑,
selectivity↑, oxidative stress threshold reached by these could be potentially higher than that caused in normal cells (tNOX−) when exposed to CAP, possibly also contributing to the selectivity of its effects
ROS↑, increase in the production of reactive oxygen species (ROS),
*ROS∅, Remarkably, in this same work, cells derived from the normal epithelium of human pancreatic ducts (HPDE6-E6E7) showed high tolerance to the same treatment by keeping their ROS levels stable
selectivity↑, In this sense, non-transformed human astrocytes from a primary culture showed greater tolerance to CAP, as they did not experience any of the mentioned effects when exposed to the same treatment

1927- JG,    Juglone-induced apoptosis in human gastric cancer SGC-7901 cells via the mitochondrial pathway
- in-vitro, GC, SGC-7901
Apoptosis↑, rate of apoptosis was found to increase in a dose-dependent manner
ROS↑, juglone at the same dose for 24h, the level of ROS was significantly higher
Bcl-2↓, Bcl-2 was significantly down-regulated and the expression of Bax was significantly up-regulated
BAX↑,
MMP↓, mitochondrial transmembrane potential was significantly lower
Cyt‑c↑, expression of the cytochrome c protein was significantly higher relative to the control
Casp3?, Caspase 3 was activated in a concentration-dependent manner
Bax:Bcl2↑, reduction in the Bcl-2/Bax ratio

1926- JG,    Mechanism of juglone-induced apoptosis of MCF-7 cells by the mitochondrial pathway
- in-vitro, BC, MCF-7
TumCG↓, Juglone inhibited the growth of MCF-7 cell line with an IC50 of 11.99 μM.
ROS↑, juglone-exposed cells exhibited significant elevation in intracellular ROS level
MMP↓, decrease in mitochondrial membrane potential
i-Ca+2↑, increase in intracellular Ca(2+) concentration
BAX↑, Juglone upregulated the expression of Bax, and downregulated the expression of Bcl-2, promoting the release of cytochrome C
Bcl-2↓,
Cyt‑c↑,
Casp3?, thereby upregulating the activity of caspase-3

2083- TQ,    Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro
- in-vitro, GC, HGC27 - in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901 - in-vivo, NA, NA
p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
JAK2↓, reduction in JAK2 and c-Src activity
c-Src↓,
Bcl-2↓, TQ also downregulated the expression of STAT3-regulated genes, such as Bcl-2, cyclin D, survivin, and vascular endothelial growth factor
cycD1/CCND1↓,
survivin↓,
VEGF↓,
Casp3?, activated caspase-3,7,9
Casp7?,
Casp9?,
*toxicity∅, A phase I study reported that in adult patients with solid tumors or hematological malignancies who were treated with TQ, there were no significant systemic toxicities[10].
TumVol↓, Thymoquinone inhibits tumor growth in a gastric mouse xenograft model.


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 ⓘ

ATF3↑, 1,   GSR↑, 1,   HO-1↑, 1,   lipid-P↑, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS↑, 4,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   mitResp↓, 1,   MMP↓, 4,  

Core Metabolism/Glycolysis ⓘ

LDHA↓, 1,   NADPH↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Casp3?, 4,   cl‑Casp3↑, 1,   Casp7?, 1,   Casp9?, 1,   cl‑Casp9↑, 1,   Chk2↓, 1,   Cyt‑c↑, 3,   HEY1↓, 1,   MAPK↑, 1,   Mcl-1↓, 1,   p38↑, 1,   survivin↓, 1,   TRPV1↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

H3↑, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 2,   HSP90↓, 1,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   P53↑, 1,   PARP↑, 1,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   CDK4↓, 2,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   FOXO3↑, 1,   NOTCH↓, 1,   c-Src↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 1,   i-Ca+2↑, 1,   ER-α36↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   Snail↓, 1,   uPA↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   PDGFR-BB↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   JAK2↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 3,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

E6↓, 1,   E7↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   RenoP↑, 1,   TumVol↓, 1,  
Total Targets: 86

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Prx↑, 1,   ROS∅, 1,   SOD2↑, 1,  

Cell Death ⓘ

Casp3?, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 6

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
2 Juglone
1 Ashwagandha(Withaferin A)
1 Capsaicin
1 Thymoquinone
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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