Propyl gallate / Casp3 Cancer Research Results

PG, Propyl gallate: Click to Expand ⟱
Features:
An ester formed by the condensation of gallic acid and propanol.
Propyl gallate (PG), chemically known as propyl-3,4,5-trihydroxybenzoate, is widely present in processed food and cosmetics, hair products, and lubricants.
PG alone demonstrated antioxidative and cytoprotective properties against cellular damage and gained a pro-oxidative property in combination with copper (II). It was reported that PG was one of the most active compounds capable of generating H2O2 in DMEM media
Main cancer-relevant pathways modulated by propyl gallate
A. Redox imbalance & oxidative stress (dominant)
-↑ Intracellular ROS (context- and dose-dependent)
  -Pro-oxidant in cancer cells with high basal ROS
  -Mitochondrial superoxide accumulation
  -Thiol depletion (↓ GSH, ↓ Trx buffering capacity)
Importance: ★★★★★  (Primary mechanism)

B. Mitochondrial dysfunction & intrinsic apoptosis
-↑ MOMP → caspase cascade
  -Loss of mitochondrial membrane potential (ΔΨm)
  -Cytochrome-c release
  -Caspase-9 → caspase-3 activation
  -↑ Bax / ↓ Bcl-2 ratio
Importance: ★★★★☆

C. ER stress & unfolded protein response (UPR)
-↑ PERK–eIF2α–ATF4–CHOP
  -ROS-linked protein misfolding
  -Pro-apoptotic UPR signaling dominates over adaptive UPR
Importance: ★★★☆☆

D. Cell cycle disruption
-G1 or G2/M arrest (cell-type dependent)
  -↓ Cyclin D1, Cyclin B1
  -↑ p21, p27
Importance: ★★☆☆☆

E. MAPK stress signaling
-↑ JNK / p38
  -Stress-activated apoptosis signaling
  -Often precedes mitochondrial failure
Importance: ★★☆☆☆

F. Inflammation & survival pathways (secondary)
-↓ NF-κB, ↓ STAT3 (indirect)
  -Suppression is largely ROS-mediated, not direct inhibition
  -Reduced anti-apoptotic gene transcription
Importance: ★★☆☆☆

G. NRF2–ARE signaling (dual role)
-Low dose: NRF2 activation → cytoprotection
  -High dose / cancer cells: NRF2 overwhelmed → apoptosis
Importance: ★★☆☆☆
(Highly context dependent; double-edged)


Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Glutathione (GSH) redox buffering ↓ GSH (depletion) Upstream redox vulnerability Leukemia and HeLa models report GSH depletion as an early, causal event in PG-induced cytotoxicity (ref)
2 Nrf2 antioxidant-response axis ↓ Nrf2 nuclear translocation → ↓ γ-GCS Impaired antioxidant capacity PG inhibits Nrf2 nuclear translocation and downstream glutathione-synthesis control, linking to GSH depletion and apoptosis in leukemia cells (ref)
3 Reactive oxygen species (ROS) balance (context-dependent) ↑ ROS (tumor models) / ↓ ROS (TMZ-combo migration model) Oxidative-stress modulation PG increases ROS in hepatocellular carcinoma (HCC) with autophagy/apoptosis; in TMZ-treated glioma, PG inhibits TMZ-induced ROS linked to reduced migration (ref)
4 MAPK stress signaling (ERK/JNK/p38) ↑ MAPK activation Stress-to-death signaling PG activates MAPKs; authors position MAPKs/Nrf2-mediated GSH depletion as an early driver of apoptosis (ref)
5 Autophagy program (LC3 conversion) ↑ autophagy Stress response contributing to growth inhibition HCC study: PG induces ROS and activates autophagy (LC3-I→LC3-II), with associated apoptosis markers (ref)
6 Apoptosis (caspase cascade; intrinsic/extrinsic components) ↑ caspase activation / ↑ apoptosis Programmed cell death Leukemia: caspases-3/8/9 activation with p53/Bax/Fas/FasL changes; lung cancer: caspase-dependent apoptosis with PARP cleavage (ref)
7 Cell-cycle regulation ↑ G1 arrest (e.g., ↑ p27) Proliferation blockade HeLa and lung cancer models report PG-induced G1 phase arrest with cell-cycle regulator changes (ref)
8 Lung cancer growth suppression ↓ proliferation / ↓ viability Anti-growth effect PG reduces growth of Calu-6 and A549 lung cancer cells with G1 arrest and caspase-dependent apoptosis (ref)
9 Migration / invasion phenotype (TMZ-combination glioma model) ↓ migration (via ↓ TMZ-induced ROS; NF-κB pathway implicated in full paper title) Anti-migratory effect (combination context) TMZ + PG enhances inhibition of U87MG glioma migration; abstract states PG inhibits TMZ-induced ROS and implicates mitochondrial complex III / NADPH oxidase as ROS sources (ref)
10 In vivo anti-tumor effect (HCC; zebrafish model) ↓ tumor growth / ↓ proliferation Demonstrated in vivo activity HCC study includes in vivo suppression (zebrafish) alongside ROS increase and autophagy activation (ref)


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⟱
1768- PG,    Propyl gallate reduces the growth of lung cancer cells through caspase‑dependent apoptosis and G1 phase arrest of the cell cycle
- in-vitro, Lung, Calu-6 - in-vitro, Lung, A549
TumCG↓, TumCCA↑, Dose∅, Bcl-2↓, cl‑PARP↑, MMP↓, Casp3↑, Casp8↑,
5217- PG,    Role of redox signaling regulation in propyl gallate-induced apoptosis of human leukemia cells
- in-vitro, AML, THP1 - in-vitro, AML, Jurkat - in-vitro, AML, HL-60
tumCV↓, Casp3↑, Casp8↑, Casp9↑, P53↑, BAX↑, Fas↑, FasL↑, MAPK↑, NRF2↓, GSH↓,
5218- PG,    Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy
- in-vitro, HCC, Hep3B
TumCP↓, Apoptosis↑, ROS↑, TumAuto↑, cl‑Casp3↑, cl‑PARP↑, BAX↑, BAD↑, Bcl-2↓, toxicity↓, hepatoP↑, GSH↓,
5219- PG,    Propyl gallate inhibits the growth of HeLa cells via caspase-dependent apoptosis as well as a G1 phase arrest of the cell cycle
- in-vitro, Cerv, HeLa
TumCG↓, TumCCA↑, p27↑, Apoptosis↑, MMP↓, Casp3↑, Casp8↑, cl‑PARP↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 2,   NRF2↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics

MMP↓, 2,  

Cell Death

Apoptosis↑, 2,   BAD↑, 1,   BAX↑, 2,   Bcl-2↓, 2,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 3,   Casp9↑, 1,   Fas↑, 1,   FasL↑, 1,   MAPK↑, 1,   p27↑, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

P53↑, 1,   cl‑PARP↑, 3,  

Cell Cycle & Senescence

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

TumCG↓, 2,  

Migration

TumCP↓, 1,  

Drug Metabolism & Resistance

Dose∅, 1,  

Functional Outcomes

hepatoP↑, 1,   toxicity↓, 1,  
Total Targets: 26

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
4 Propyl 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
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:138  Target#:42  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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