Database Query Results : Propolis -bee glue, , Warburg

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)
Warburg, Warburg Effect: Click to Expand ⟱
Source:
Type: effect

The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring.

Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate.

Warburg effect (GLUT1, LDHA, HK2, and PKM2).
Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export).

Here are some of the key pathways and potential targets:

Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓

1.Glycolysis Inhibitors:(2-DG, 3-BP)
- HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis
-PFK1 Inhibitors: such as PFK-158, can reduce glycolysis
-PFKFB Inhibitors:
- PKM2 Inhibitors: (Shikonin)
-Can reduce glycolysis
- LDH Inhibitors: (Gossypol, FX11)
-Reducing the conversion of pyruvate to lactate.
-Inhibiting the production of ATP and NADH.
- GLUT1 Inhibitors: (phloretin, WZB117)
-A key transporter involved in glucose uptake.
-GLUT3 Inhibitors:
- PDK1 Inhibitors: (dichloroacetate)
- A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure.

2.Pentose phosphate pathway:
- G6PD Inhibitors: can reduce the pentose phosphate pathway

3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway:
- HIF1α inhibitors: (PX-478,Shikonin)
-Reduce expression of glycolytic genes and inhibit cancer cell growth.

4.AMP-activated protein kinase (AMPK) pathway:
-AMPK activators: (metformin,AICAR,berberine)
-Can increase AMPK activity and inhibit cancer cell growth.

5.mTOR pathway:
- mTOR inhibitors:(rapamycin,everolimus)
-Can reduce mTOR activity and inhibit cancer cell growth.

Warburg Targeting Matrix (Cancer Metabolism)

Node What It Does (Warburg role) Representative Inhibitors / Modulators Mechanism Snapshot Typical Tumor Effects Best-Fit Tumor Context Common Constraints / Gotchas TSF Combination Logic
GLUT (glucose uptake)
GLUT1 (SLC2A1) focus		 Controls glucose entry; sets the upper bound on glycolytic flux. Research/repurposing: WZB117 (GLUT1), BAY-876 (GLUT1), STF-31 (GLUT1 tool), Fasentin (GLUT), Phloretin (broad, weak)
Dietary/indirect: some polyphenols reported to lower GLUT1 expression (context) 		Blocks glucose transport or reduces GLUT1 expression → less substrate for glycolysis & PPP. ATP stress (in highly glycolytic tumors), lactate ↓, growth slowdown; can sensitize to stressors. High-GLUT1 tumors; hypoxic / glycolysis-addicted phenotypes. Systemic glucose handling and glucose-dependent tissues; tumor compensation via alternate fuels. P, R Pairs with ROS/ETC stressors or LDH/MCT blockade; beware compensatory glutaminolysis/fatty acid oxidation.
Hexokinase (HK2)
first committed glycolysis step		 Traps glucose as G-6-P; HK2 often upregulated and mitochondria-associated in tumors. Clinical/adjunct interest: 2-Deoxyglucose (2-DG; glycolysis + glycosylation stress)
Research: Lonidamine-class glycolysis axis drugs (not “pure HK2”), 3-bromopyruvate (hazardous research agent; not for casual use) 		Competitive substrate mimic (2-DG) → 2-DG-6P accumulation; HK flux ↓; ER glycosylation stress ↑. ATP ↓, AMPK ↑, ER stress/UPR ↑, autophagy ↑, apoptosis (context); radiosensitization reported. Highly glycolytic tumors; tumors with strong HK2 dependence; hypoxic cores. Normal glucose-dependent tissues; ER-stress toxicities; dosing/tolerability limits in practice. P, R, G Pairs with radiation, pro-oxidant stress, or MCT/LDH blockade; watch systemic glucose effects.
LDH (LDHA/LDHB)
pyruvate ⇄ lactate		 Regenerates NAD+ to sustain glycolysis; LDHA supports lactate production and acidification. Tier A direct inhibitors: FX11, (R)-GNE-140, NCI-006, Oxamate, Galloflavin, Gossypol
Tier B indirect: polyphenols (often lactate/LDH expression ↓ rather than catalytic inhibition) 		Blocks LDH catalysis → NAD+ recycling ↓ → glycolysis throttles; pyruvate handling shifts; redox pressure ↑. Lactate ↓, glycolytic flux ↓, oxidative stress ↑ (often secondary), growth inhibition; immune microenvironment may improve if lactate decreases. LDHA-high tumors; lactate-driven immunosuppression; glycolysis-addicted phenotypes. Metabolic plasticity: tumors switch fuels; some LDH inhibitors have PK liabilities; “LDH release” ≠ LDH inhibition. R, G Pairs with MCT inhibition (trap lactate), NAD+ axis inhibitors, immune therapy (lactate suppression logic), and OXPHOS stressors (context).
MCT (lactate transport)
MCT1 (SLC16A1), MCT4 (SLC16A3)		 Exports lactate + H+ (acidifies TME); enables lactate shuttling between tumor subclones. Clinical-stage: AZD3965 (MCT1 inhibitor; clinical trials)
Research: AR-C155858 (MCT1/2), Syrosingopine (MCT1/4; repurposed), Lonidamine (MCT + MPC axis) 		Blocks lactate export/import → intracellular acid stress ↑ (in glycolytic cells) and lactate shuttling ↓. Acid stress, growth inhibition; may improve immune function by reducing lactate/acidic suppression (context). MCT1-high tumors; oxidative “lactate-using” tumor fractions; tumors with lactate shuttling. MCT4-driven export can bypass MCT1-only inhibitors; hypoxia upregulates MCT4; need target matching. P, R Pairs strongly with LDH inhibitors (cut production + block export), and with immune therapy rationale (lactate/acid microenvironment).
PDK (PDK1-4)
PDH gatekeeper		 PDK inhibits PDH → keeps pyruvate out of mitochondria; supports Warburg by favoring lactate. Prototype: Dichloroacetate (DCA; pan-PDK inhibitor “classic”)
Research: AZD7545 (PDK2 inhibitor; tool), newer PDK inhibitor series (research) 		Inhibits PDK → PDH active ↑ → pyruvate into TCA/OXPHOS ↑; lactate pressure ↓. Warburg reversal pressure (context), lactate ↓, mitochondrial flux ↑; can increase ROS in some settings (secondary). PDK-high tumors; tumors with suppressed PDH flux; “glycolysis locked” metabolic phenotype. Requires functional mitochondrial capacity; hypoxia can limit OXPHOS shift; effect is often modulatory rather than directly cytotoxic. R, G Pairs with therapies that exploit mitochondrial dependence or redox stress; can complement LDH/MCT strategies by reducing lactate drive.

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

  • P: 0–30 min (direct transport/enzyme flux effects begin)
  • R: 30 min–3 hr (acute ATP/NAD+/acid stress and signaling changes)
  • G: >3 hr (gene adaptation, phenotype outcomes, immune/TME effects)
Scientific Papers found: Click to Expand⟱

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 0

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Warburg, Warburg Effect
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#:947  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page