Propolis -bee glue / Casp3 Cancer Research Results

PBG, Propolis -bee glue: Click to Expand ⟱
Features: Compound
Brazilian Green Propolis often considered best
• Derived from Baccharis dracunulifolia, this type is rich in artepillin C.
• It has been widely researched for its anticancer, anti-inflammatory, and antioxidant properties.
-Propolis common researched flavonoids :chrysin, pinocembrin, galangin, pinobanksin(Pinocembrin)
-most representative phenolic acids were caffeic acid, p-coumaric acid, and ferulic acid, as well as their derivatives, DMCA and caffeic acid prenyl, benzyl, phenylethyl (CAPE), and cinnamyl esters
-One of the most studied active compounds of a poplar-type propolis is caffeic acid phenethyl ester (CAPE)
-caffeic acid phenethyl ester (CAPE), galangin, chrysin, nemorosone, propolin G, artepillin C, cardanol, pinocembrin, pinobanksin, chicoric acid, and phenolic acids (caffeic acid, ferulic acid, and coumaric acid), as well as luteolin, apigenin, myricetin, naringenin, kaempferol, quercetin, polysaccharides, tannins, terpenes, sterols, and aldehydes -content highly variable based on location and extraction
Two main factors of interest:
1. affects interstitual fluild pH
2. high concentration raises ROS (Reactive Oxygen Species), while low concentration may reduce ROS

- Artepillin-C (major phenolic compounds found in Brazilian green propolis (BGP))
- caffeic acid major source

Propolis is chemically diverse (300+ compounds reported) and composition depends on botanical/geographic source.
Antibacterial activity is documented in classic literature (often stronger against Gram+).
CAPE from propolis has reported preferential tumor cytotoxicity in early landmark work (often cited in antimicrobial paper references)

Do not combine with 2DG

Pathways:
-Propolis compounds (e.g., artepillin C, caffeic acid phenethyl ester [CAPE]) can trigger apoptosis (programmed cell death) in cancer cells.
-Propolis has been shown to inhibit NF‑κB activation.
-Propolis extracts can cause cell cycle arrest at specific checkpoints (e.g., G0/G1 or G2/M phases).
-Enhance the body’s antitumor immune responses, for example by activating natural killer (NK) cells and modulating cytokine profiles.

-Note half-life no standard, high variablity of content.
BioAv poor water solubility, and low oral bioavailability.
Pathways:
- high concentration may induce ROS production, while low concentrations mya low it. This may apply to both normal and cancer cells. Normal Cells Example. (Also not sure if high level are acheivable in vivo due to bioavailability)
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓ -->
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : NLRP3↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, P53↑,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓,
- Others: PI3K↓, AKT↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS / redox stress (context-selective) Often ↑ ROS / oxidative stress susceptibility (P→R→G) Often antioxidant / cytoprotective in inflammatory stress contexts (R→G) P, R, G Stress amplifier / selectivity gate Net ROS direction is highly context- and extract-dependent; propolis chemistry varies by geography/plant source and can shift redox behavior.
2 NF-κB inflammatory transcription ↓ NF-κB activity (R→G) Anti-inflammatory signaling in immune/tissue contexts (R→G) R, G Anti-inflammatory / anti-survival transcription A common “hub” claim across propolis literature; contributes to reduced cytokine/pro-survival programs.
3 Intrinsic apoptosis (mitochondria → caspases) ↑ apoptosis; ↑ caspase activation (G) ↔ (usually less activation) G Cell death execution Often downstream of sustained stress signaling and/or survival pathway suppression.
4 MAPK re-wiring (ERK / p38 / JNK) Stress MAPK shifts; JNK/p38 often ↑ with stress (P→R); ERK variable ↔ / context-dependent P, R, G Signal reprogramming MAPK directions depend on extract composition, dose, and tumor type; best described as “re-wiring” rather than fixed arrows for ERK.
5 PI3K → AKT (± mTOR) ↓ PI3K/AKT survival signaling (R→G) ↔ R, G Growth/survival suppression Often reported alongside reduced proliferation and increased apoptosis susceptibility.
6 Nrf2 / antioxidant response (HO-1, GSH enzymes) Context-dependent (may be ↓ in tumor-stress settings; may be ↑ as adaptation) Often ↑ protective antioxidant response under stress R, G Adaptive buffering Nrf2 direction is not universal; avoid absolute “Nrf2 always ↑/↓” statements for propolis.
7 Angiogenesis (VEGF and related factors) ↓ angiogenic signaling outputs (G) ↔ G Anti-angiogenic support Usually shows up in later gene-expression / phenotype assays rather than early signaling.
8 EMT / invasion / migration (MMPs, EMT markers) ↓ EMT / ↓ migration & invasion programs (G) ↔ G Anti-invasive phenotype Often measured as reduced MMP activity and reduced migration/invasion phenotypes; timing tends to be later.
9 Antimicrobial / microbiome-relevant effects Indirect (may reduce infection-driven inflammation) Direct antimicrobial activity (context) R, G Host-protective / anti-infective Propolis has documented antibacterial activity (stronger vs many Gram+ than Gram− in classic reports), which can matter for inflammation-linked biology.
10 Key bioactives (CAPE; flavonoids/phenolics) CAPE-class compounds: tumor-selective cytotoxicity reported (G) ↔ G “Active fraction” concept Propolis is a mixture; effects may be driven by a few high-impact phenolics (e.g., CAPE) and vary by extract standardization.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (primary/physical–chemical effects; rapid signaling / phosphorylation shifts)
  • R: 30 min–3 hr (redox signaling + acute stress-response signaling)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
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⟱
5771- CAPE,  PBG,    Caffeic acid phenethyl ester: Unveiling its potential as a potent apoptosis inducer for combating hypopharyngeal squamous cell carcinoma
- in-vitro, HNSCC, NA
MMP↓, Casp3↑, survivin↓, XIAP↓,
1644- HCAs,  PBG,    Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) sensitizes LNCaP prostate cancer cells to TRAIL-induced apoptosis
- in-vitro, Pca, LNCaP
NF-kB↓, TRAILR↑, Casp8↑, Casp3↑, MMP↓, Dose?,
2430- PBG,    The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation
- in-vitro, BC, MDA-MB-231
TumCP↓, TP53↓, Casp3↓, BAX↓, P21↓, ROS↑, eff↓, MMP↓, LDH↑, ATP↓, Ca+2↑,
1672- PBG,    The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers
- Review, BC, NA
ChemoSen↓, RadioS↑, Inflam↓, AntiCan↑, Dose∅, mtDam↑, Apoptosis?, OCR↓, ATP↓, ROS↑, ROS↑, LDH↓, TP53↓, Casp3↓, BAX↓, P21↓, ROS↑, eNOS↑, iNOS↑, eff↑, hTERT/TERT↓, cycD1/CCND1↓, eff↑, eff↑, eff↑, eff↑, STAT3↓, TIMP1↓, IL4↓, IL10↓, OS↑, Dose∅, ER Stress↑, ROS↑, NF-kB↓, p65↓, MMP↓, TumAuto↑, LC3II↑, p62↓, TLR4↓, mtDam↑, LDH↓, ROS↑, Glycolysis↓, HK2↓, PFK↓, PKM2↓, LDH↓, IL10↓, HDAC8↓, eff↑, eff↑, P21↑,
1660- PBG,    Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents
- Review, Var, NA
MMPs↓, angioG↓, TumMeta↓, TumCCA↑, Apoptosis↑, ChemoSideEff↓, eff∅, HDAC↓, PTEN↑, p‑PTEN↓, p‑Akt↓, Casp3↑, p‑ERK↑, p‑FAK↑, Dose?, Akt↓, GSK‐3β↓, FOXO3↓, eff↑, IL2↑, IL10↑, NF-kB↓, VEGF↓, mtDam↑, ER Stress↑, AST↓, ALAT↓, ALP↓, COX2↓, eff↑, Bax:Bcl2↑,
1663- PBG,    Propolis and Their Active Constituents for Chronic Diseases
- Review, Var, NA
NF-kB↓, Casp↓, Fas↓, DNAdam↑, Casp3↑, P53↝, MMP↝, ROS↑, mtDam↑, Dose?, angioG↓, TumCP↓, TumCMig↓, BAX↑, selectivity↑, MMP↓, LDH↓, IL6↓, IL1β↓, TNF-α↓,
1664- PBG,    Anticancer Activity of Propolis and Its Compounds
- Review, Var, NA
Apoptosis↑, TumCMig↓, TumCCA↑, TumCP↓, angioG↓, P21↑, p27↑, CDK1↓, p‑CDK1↓, cycA1/CCNA1↓, CycB/CCNB1↓, P70S6K↓, CLDN2↓, HK2↓, PFK↓, PKM2↓, LDHA↓, TLR4↓, H3↓, α-tubulin↓, ROS↑, Akt↓, GSK‐3β↓, FOXO3↓, NF-kB↓, cycD1/CCND1↓, MMP↓, ROS↑, i-Ca+2↑, lipid-P↑, ER Stress↑, UPR↑, PERK↑, eIF2α↑, GRP78/BiP↑, BAX↑, PUMA↑, ROS↑, MMP↓, Cyt‑c↑, cl‑Casp8↑, cl‑Casp8↑, cl‑Casp3↑, cl‑PARP↑, eff↑, eff↑, RadioS↑, ChemoSen↑, eff↑,
1668- PBG,    Propolis: A Detailed Insight of Its Anticancer Molecular Mechanisms
- Review, Var, NA
antiOx↑, Inflam↓, AntiCan↑, TumCP↓, Apoptosis↑, eff↝, MMPs↓, TNF-α↓, iNOS↓, COX2↓, IL1β↑, *BioAv↓, BAX↑, Casp3↑, Cyt‑c↑, Bcl-2↓, eff↑, selectivity↑, P53↑, ROS↑, Casp↑, eff↑, ERK↓, Dose∅, TRAIL↑, NF-kB↑, ROS↑, Dose↑, MMP↓, DNAdam↑, TumAuto↑, LC3II↑, p62↓, EGF↓, Hif1a↓, VEGF↓, TLR4↓, GSK‐3β↓, NF-kB↓, Telomerase↓, ChemoSen↑, ChemoSideEff↓,
1675- PBG,    Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
- in-vitro, Melanoma, A375 - in-vitro, Melanoma, WM983B
tumCV↓, ROS↑, antiOx↑, Apoptosis↑, BAX↑, P53↑, Casp3↑, Casp9↑,
1676- PBG,    Use of Stingless Bee Propolis and Geopropolis against Cancer—A Literature Review of Preclinical Studies
- Review, Var, NA
ROS↑, MMP↓, Bcl-2↓, eff↑, tumCV↓, TumCCA↑, angioG↓, PAK1↓, HDAC1↓, HDAC2↓, P53↑, PCNA↓, cycD1/CCND1↓, cycE/CCNE↓, P21?, BAX↑, cl‑Casp3↑, cl‑PARP↑, ChemoSen↑,
1677- PBG,    Propolis Inhibits UVA-Induced Apoptosis of Human Keratinocyte HaCaT Cells by Scavenging ROS
- in-vitro, Nor, HaCaT
*Dose∅, *AP-1↓, *MMP↑, *Casp3↓, *ROS↓,
1678- PBG,  5-FU,  sericin,    In vitro and in vivo anti-colorectal cancer effect of the newly synthesized sericin/propolis/fluorouracil nanoplatform through modulation of PI3K/AKT/mTOR pathway
- in-vitro, CRC, Caco-2 - in-vivo, NA, NA
PI3K↓, Akt↓, mTOR↓, TumCP↓, Bcl-2↓, BAX↑, Casp3↑, Casp9↑, ROS↓, FOXO1↑, *toxicity∅, eff↑,
1679- PBG,    Constituents of Propolis: Chrysin, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid Induce PRODH/POX-Dependent Apoptosis in Human Tongue Squamous Cell Carcinoma Cell (CAL-27)
- in-vitro, SCC, CAL27
tumCV↓, P53↑, Casp9↑, Casp3↑, GSH↓, proline↓,
1680- PBG,    Protection against Ultraviolet A-Induced Skin Apoptosis and Carcinogenesis through the Oxidative Stress Reduction Effects of N-(4-bromophenethyl) Caffeamide, a Propolis Derivative
- in-vitro, Nor, HS68
*ROS↓, *NRF2↑, *HO-1↑, *cJun↓, *MMP1↓, *MMP2↓, *p‑cJun↓, *cFos↓, *BAX↓, *Casp3↓, *DNAdam↓, *iNOS↓, *COX2↓, *IL6↓, *PGE2↓, *NO↓,
1682- PBG,    Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits
- Review, Var, NA
i-LDH↓, Akt↓, MAPK↓, NF-kB↓, IL1β↓, IL6↓, TNF-α↓, iNOS↓, COX2↓, ROS↓, Bcl-2↓, PARP↓, P53↑, BAX↑, Casp3↑, TumCCA↑, Cyt‑c↑, MMP↓, eff↑,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↓, 1,   lipid-P↑, 1,   ROS↓, 2,   ROS↑, 14,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   EGF↓, 1,   MMP↓, 10,   MMP↝, 1,   mtDam↑, 4,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   Glycolysis↓, 1,   HK2↓, 2,   LDH↓, 4,   LDH↑, 1,   i-LDH↓, 1,   LDHA↓, 1,   PFK↓, 2,   PKM2↓, 2,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↓, 1,   Apoptosis?, 1,   Apoptosis↑, 4,   BAX↓, 2,   BAX↑, 7,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Casp↓, 1,   Casp↑, 1,   Casp3↓, 2,   Casp3↑, 9,   cl‑Casp3↑, 2,   Casp8↑, 1,   cl‑Casp8↑, 2,   Casp9↑, 3,   Cyt‑c↑, 3,   Fas↓, 1,   hTERT/TERT↓, 1,   iNOS↓, 2,   iNOS↑, 1,   MAPK↓, 1,   p27↑, 1,   PUMA↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TRAIL↑, 1,   TRAILR↑, 1,  

Transcription & Epigenetics ⓘ

H3↓, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 1,   ER Stress↑, 3,   GRP78/BiP↑, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 2,   p62↓, 2,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 5,   P53↝, 1,   PARP↓, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   TP53↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   p‑CDK1↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21?, 1,   P21↓, 2,   P21↑, 2,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   p‑ERK↑, 1,   FOXO1↑, 1,   FOXO3↓, 2,   GSK‐3β↓, 3,   HDAC↓, 1,   HDAC1↓, 1,   HDAC2↓, 1,   HDAC8↓, 1,   mTOR↓, 1,   P70S6K↓, 1,   PI3K↓, 1,   PTEN↑, 1,   p‑PTEN↓, 1,   STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   i-Ca+2↑, 1,   CLDN2↓, 1,   p‑FAK↑, 1,   MMPs↓, 2,   PAK1↓, 1,   proline↓, 1,   TIMP1↓, 1,   TumCMig↓, 2,   TumCP↓, 5,   TumMeta↓, 1,   α-tubulin↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   eNOS↑, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IL10↓, 2,   IL10↑, 1,   IL1β↓, 2,   IL1β↑, 1,   IL2↑, 1,   IL4↓, 1,   IL6↓, 2,   Inflam↓, 2,   NF-kB↓, 7,   NF-kB↑, 1,   p65↓, 1,   TLR4↓, 3,   TNF-α↓, 3,  

Drug Metabolism & Resistance ⓘ

ChemoSen↓, 1,   ChemoSen↑, 3,   Dose?, 3,   Dose↑, 1,   Dose∅, 3,   eff↓, 1,   eff↑, 17,   eff↝, 1,   eff∅, 1,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   hTERT/TERT↓, 1,   IL6↓, 2,   LDH↓, 4,   LDH↑, 1,   i-LDH↓, 1,   TP53↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   ChemoSideEff↓, 2,   OS↑, 1,  
Total Targets: 144

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   NRF2↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Casp3↓, 2,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   p‑cJun↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,  

Migration ⓘ

AP-1↓, 1,   MMP1↓, 1,   MMP2↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL6↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose∅, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 22

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
15 Propolis -bee glue
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Hydroxycinnamic-acid
1 5-fluorouracil
1 sericin
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#:137  Target#:42  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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