CTSD Cancer Research Results

CTSD, Cathepsin D: Click to Expand ⟱
Source:
Type:
CTSD — Cathepsin D

Primary role: Lysosomal aspartyl protease; regulator of autophagic degradation and stress-adaptive survival signaling.

Cancer relevance:
CTSD supports lysosomal proteolysis and autophagic completion, enabling metabolic recycling under stress. In cancer, it is often overexpressed and can function both intracellularly (autophagy, apoptosis modulation) and extracellularly (growth factor processing). Partial lysosomal leakage of CTSD contributes to apoptotic signaling, while intact activity promotes therapy resistance.

Net effect in established cancer:
Predominantly pro-survival via maintenance of autophagic flux, with pro-apoptotic potential under severe stress.
Scientific Papers found: Click to Expand⟱
5173- Ash,  2DG,    Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells
- in-vitro, BC, MCF7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, T47D
autoF↓, WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells.
lysosome↓, WFA treatment inhibits lysosomal activity
TumAuto↑, WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion.
p‑LDH↓, WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion
ATP↓, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation.
AMPK↑,
eff↑, WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells.
TumCG↓, WFA inhibits breast cancer growth and increases intracellular autophagosomes and autophagy markers
CTSD↓, we found that WFA impaired the maturation of Cathepsin D (CTSD)
CTSB↓, Inhibition of CTSD maturation also indicated reduced CTSB and CTSL activity as they are essential for the cleavage of CTSD.
CTSL↑,
cl‑PARP1↑, WFA and 2-DG treatment also showed higher cleavage of PARP1 in breast cancer cells
LDHA↓, WFA treatment effectively reduces the expression of LDHA in breast cancer cells
TCA↓, d leads to insufficient substrates for TCA cycle,

8105- KAE,    Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review
- Review, Var, NA
Apoptosis↑, It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT
tumCV↓,
TumCCA↑,
PI3K↓,
Akt↓,
EMT↓, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2).
N-cadherin↓,
E-cadherin↓, nhibition of N‐cadherin, E‐cadherin, Slug, Snail, and MMP‐2, 9, and cathepsin B, D
Slug?,
Snail?,
MMP2↓,
MMP9↓,
CTSB↓,
CTSD↓,
Casp3↑, Activation of caspase signals such as caspase‐3, ‐8, and ‐9
Casp8↑,
Casp9↑,
TIMP2↓, Down‐regulation of phosphorylated TIMP2, AKT, and MMP2 levels
Akt↓,
TumCD↑, Induction of cell apoptotic cell death, intracellular free calcium elevation, and mitochondrial membrane potential disruption.
i-Ca+2↑,
MMP↓,
*ROS↓, Enhances the concentrations of superoxide dismutase, catalase, glutathione peroxidase, and glutathione‐S‐transferase.
*SOD↑,
*Catalase↑,
*GPx↑,
*GSTs↑,
*AST↓, Lowers aspartate aminotransferase, alanine aminotransferase, malondialdehyde (MDA).
*ALAT↓,
*MDA↓,
*CYP2E1↓, Decreases activity of hepatic microsomal enzyme cytochrome 2E1 (CYP2E1) expression
*NRF2↑, Increases mRNA and protein expression of Nrf2‐regulated genes
*AGEs↓, Suppresses advanced glycation end products (AGEs)‐ receptor.
*IL6↓, Reduces levels of IL‐6, TNF‐α, and NF‐κB.
*TNF-α↓,
*NF-kB↓,
*Casp3↓, Lowers expressions of Caspase‐3 and Bax,
*BAX↓,
*antiAll↑, Antiallergic Inhibits COX2‐mediated production of prostaglandin D2 and prostaglandin F2α.
*COX2/PTGS2↓,
*PGE2↓,
*RUNX2↑, Increases expression of the osteoblast‐activated factors RUNX‐2, BMP‐2, osterix, collagen I, and SQSTM1/p62
*BMP2↑,
*COL1↑,
*p62↑,
*FASN↓, Reduces expressions of lipin1, FASN, LPAATθ (lysophosphatidic acid acyltransferase), SREBP‐1C (fatty acid synthetic proteins), and DGAT1 (triglyceride synthetic enzymes).
*DGAT1↓,
FOXP3↑, kaempferol significantly enhanced the inhibitory effect of proliferation, increased the FOXP3 expression level,
DNAdam↑, s induction of DNA damage, enhancement DNA condensation
ROS↑, anti‐cancer property is mainly defined by ROS accumulation due to catalase inhibition as depicted in Figure 2
Catalase↓,
*ROS↓, (A/R)‐induced injury of cardiomyocytes by increasing cell viability, lowering LDH release, reducing A/R‐induced ROS generation, loss of Δψm, and release of cytochrome c from mitochondria into cytosol.
*MMP↑,
*Cyt‑c↓,

8075- KAE,  QC,    Systematic review on anticancer potential of Kaempferol and quercetin against lung, breast, and colorectal cancers with emphasis on in vitro and in vivo studies
- Review, Var, NA
tumCV↓, Both compounds consistently reduced cancer cell viability, induced apoptosis.
Apoptosis↑,
TumCP↓, They inhibited proliferation and migration by modulating the PI3K/Akt, MAPK, NF-κB, and p53 pathways across breast, lung, and colorectal cancer cell lines.
TumCMig↓,
PI3K↓,
Akt↓,
MAPK↓,
NF-kB↓,
P53↑,
Bcl-2↓, Bcl-2 downregulation and cleaved PARP activation
PARP↑,
ERK↓, kaempferol induce apoptosis by suppressing ERK1/2 pathway via IQGAP3 inhibition as well as by elevating γH2AX, cleaved caspase-3 and − 9 expression
IQGAP3↓,
γH2AX↑,
cl‑Casp3↑,
cl‑Casp9↑,
Rho↓, It reduced RhoA and Rac1 activity in MDA-MB-231 cells and countered triclosan-induced migration in MCF-7 cells by downregulating MMP-2/9 and cathepsins B and D
Rac1↓,
MMP2↓,
MMP9↓,
CTSB↓,
CTSD↓,
O-Glc↓, suppresses O-GlcNAcylation and Hsp47
SERPINH1/HSP47↓,
EMT↓, Inhibition of metastasis and epithelial-mesenchymal transition (EMT)
angioG↓, It suppresses tumor-induced angiogenesis in colorectal cancer by downregulating EGF-A/VEGFR2 pathway
EGF↓,
VEGFR2/KDR/Flk1↓,
RadioS↑, Quercetin showed anti-proliferative activity against the lung cancer cells by radio-sensitization and targeting the apoptotic mechanism.


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

IQGAP3↓, 1,   O-Glc↓, 1,   SERPINH1/HSP47↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   EGF↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   p‑LDH↓, 1,   LDHA↓, 1,   TCA↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   Apoptosis↑, 2,   Bcl-2↓, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   MAPK↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

autoF↓, 1,   lysosome↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,   PARP↑, 1,   cl‑PARP1↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CTSB↓, 3,   CTSD↓, 3,   CTSL↑, 1,   EMT↓, 2,   ERK↓, 1,   PI3K↓, 2,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

i-Ca+2↑, 1,   E-cadherin↓, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   Rac1↓, 1,   Rho↓, 1,   Slug?, 1,   Snail?, 1,   TIMP2↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   VEGFR2/KDR/Flk1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

FOXP3↑, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

p‑LDH↓, 1,  
Total Targets: 58

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

antiAll↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   CYP2E1↓, 1,   GPx↑, 1,   GSTs↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   DGAT1↓, 1,   FASN↓, 1,  

Cell Death(tgid=5) ⓘ

BAX↓, 1,   BMP2↑, 1,   Casp3↓, 1,   Cyt‑c↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

p62↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

RUNX2↑, 1,  

Migration(tgid=13) ⓘ

COL1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL6↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   IL6↓, 1,  
Total Targets: 29

Scientific Paper Hit Count for: CTSD, Cathepsin D
2 Kaempferol
1 Ashwagandha(Withaferin A)
1 2-DeoxyGlucose
1 Quercetin
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#:1430  State#:%  Dir#:1
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