condition found tbRes List
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

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


P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.
Scientific Papers found: Click to Expand⟱
1651- CA,  PBG,    Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer
- Review, Var, NA
Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 μM) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

1682- PBG,    Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits
- Review, Var, NA
i-LDH↓, cytotoxic activities of Tualang honey in human breast cancer cells were demonstrated by elevated secretion of lactate dehydrogenase (LDH)
Akt↓, figure 2
MAPK↓, figure 2
NF-kB↓, figure 2
IL1β↓, figure 2
IL6↓, figure 2
TNF-α↓, figure 2
iNOS↓, figure 2
COX2↓, figure 2
ROS↓, figure 2
Bcl-2↓, figure 2
PARP↓, figure 2
P53↑, figure 2
BAX↑, figure 2
Casp3↑, figure 2
TumCCA↑, Several components of honey such as chrysin, quercetin, and kaempferol have been shown to arrest cell cycle at various phases such as G0/G1, G1, and G2/M
Cyt‑c↑, hese stimuli cause several proteins located within the intermembrane space (IMS) of the mitochondria, such as cytochrome c, to be released
MMP↓, Honey induces MOMP in cancer cell lines by decreasing the mitochondrial membrane potential
eff↑, amplifying the apoptotic effect of tamoxifen by intensified depolarization of the mitochondrial membrane.

1668- PBG,    Propolis: A Detailed Insight of Its Anticancer Molecular Mechanisms
- Review, Var, NA
antiOx↑, Propolis has well-known therapeutic actions including antioxidative, antimicrobial, anti-inflammatory, and anticancer properties.
Inflam↓,
AntiCan↑,
TumCP↓, primarily by inhibiting cancer cell proliferation, inducing apoptosis
Apoptosis↑,
eff↝, Depending on the bee species, geographic location, plant species, and weather conditions, the chemical makeup of propolis fluctuates significantly
MMPs↓, via inhibiting the metastatic protein expression such as MMPs (matrix metalloproteinases)
TNF-α↓, inhibit inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-1/2 (COX ½), lipoxygenase (LOX), prostaglandins (PGs), and interleukin 1- β (IL1-β)
iNOS↓,
COX2↓,
IL1β↑,
*BioAv↓, Despite the low bioavailability of Artepillin C, a compound with a wide variety of physiological activities
BAX↑, Egyptian propolis extract revealed high apoptotic effects through an increase in BAX (pro-apoptotic protein), caspase-3, and cytochrome-c expression levels, and by a reduction in B-cell lymphoma2 (BCL2)
Casp3↑,
Cyt‑c↑,
Bcl-2↓,
eff↑, enhanced the G0/G1 cell cycle arrest induced by methotrexate
selectivity↑, Thailand propolis on normal and cancerous cells carried out by Umthong et al. found significant differences with the propolis showing cytotoxicity against cancerous but not normal cells.
P53↑, significant increases in the levels of p53 in cells treated with propolis extracts.
ROS↑, propolis induced apoptosis in the SW620 human colorectal cancer cell line through mitochondrial dysfunction caused by high production of reactive oxygen species (ROS) and caspase activation
Casp↑,
eff↑, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
ERK↓, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
Dose∅, propolis extracts at concentrations of 50 μg/mL significantly increased the levels of TRAIL in cervical tumor cell lines
TRAIL↑,
NF-kB↑, p53, NF-κB, and ROS. These molecules were found to be elevated following exposure of the cells to the alcoholic extract of the propolis
ROS↑,
Dose↑, high concentrations, propolis increased the amounts of integrin β4, ROS, and p53
MMP↓, high expression levels of these molecules, in turn, drove a decrease in mitochondrial membrane potential
DNAdam↑, propolis extract induced DNA fragmentation
TumAuto↑, CAPE, were found to induce autophagy in a breast cancer cell line (MDA-MB-231) through upregulating LC3-II and downregulating p62,
LC3II↑,
p62↓,
EGF↓, downregulation of EGF, HIF-1α, and VEGF
Hif1a↓,
VEGF↓,
TLR4↓, downregulating Toll-like receptor 4 (TLR-4), glycogen synthase kinase 3 beta (GSK3 β), and NF-κB signaling pathways
GSK‐3β↓,
NF-kB↓,
Telomerase↓, Propolis was shown to inhibit the telomerase reverse transcriptase activity in leukemia cells.
ChemoSen↑, Propolis has been shown to increase the activity of existing chemotherapeutic agents and inhibit some of their side effects
ChemoSideEff↓,

1661- PBG,    Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways
- Review, Var, NA
JNK↓, downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB
ERK↓,
Akt↓,
NF-kB↓,
FAK↓, inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways
MAPK↓,
PI3K↓,
Akt↓,
P21↑, propolis-induced up-regulation of p21 and p27
p27↑,
TRAIL↑, effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling
BAX↑,
P53↑,
ERK↓,
ChemoSen↑, effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy
RadioS↑,
Glycolysis↓, Chinese poplar propolis decreased aerobic glycolysis by reducing the levels of crucial enzymes such as phosphofructokinase (PFK), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
HK2↓,
PKM2↓,
LDHA↓,
PFK↓,

1663- PBG,    Propolis and Their Active Constituents for Chronic Diseases
- Review, Var, NA
NF-kB↓, CAPE (a bioactive constituent of propolis) was reported to have anticancer properties by inhibiting NF-κB, caspase and Fas signaling activation in MCF-7 cells
Casp↓,
Fas↓,
DNAdam↑, DNA fragmentation, CCAAT/enhancer binding protein homologous protein expression and caspase-3 activity
Casp3↑,
P53↝, Chinese propolis (EECP) and its bioactive constituents mainly persist due to regulation of the annexin A7 and p53 proteins, mitochondrial membrane potential and ROSs, as well as that inhibition of NF-κB causes apoptosis in cancer cells
MMP↝,
ROS↑, Herrera et al. and reported on the MDA-MB 231 tumor cell line, and the inhibitory effect of propolis was proposed to occur through the induction of mitochondrial dysfunction, resulting in ROS-associated necrosis
mtDam↑,
Dose?, A concentration of 100 μg/mL was able to attain 71% cytotoxicity
angioG↓, negative effect on angiogenesis, proliferation and migration of tumor cells. A concentration of 25–200 μg/mL noticeably inhibited the metastasis of breast cancer
TumCP↓,
TumCMig↓,
BAX↑,
selectivity↑, Negligible effect in fibroblasts
MMP↓, Cuban: Disturbed the mitochondrial potential, lactate dehydrogenase released, production of ROS and cell migration
LDH↓,
IL6↓, Chinese: Decreased cell tube generation, IL-6, IL-1β, TNF-α-like inflammatory mediators, glycolytic enzymes and mitochondrial potential. Promoted ROS generation
IL1β↓,
TNF-α↓,

1673- PBG,    An Insight into Anticancer Effect of Propolis and Its Constituents: A Review of Molecular Mechanisms
- Review, Var, NA
TumCP↓, propolis-treated cells showed inhibition of cell proliferation and induction of apoptosis
Apoptosis↑,
TumCCA↑, cell cycle arrest potential against cancer cell lines
MALAT1↓, CAPE blocks the expression of the MALT1 gene to decrease the cell proliferation, invasion, and tumor growth of prostate carcinoma cells via the p53 and NF-κB signaling pathways
P53↑,
RadioS↑, Propolis capsules (400 mg, 3 times daily) is consumed for 10 days before radiotherapy, 10 days during radiation treatment, and 10 days after irradiation
OS↑, Patients who used propolis supplements had a considerably longer median disease-free lifetime.
ROS↑, Chinese propolis extract (EECP) significantly increased annexin A7 expression, ROS, NF-κB, and p65 expressions and dramatically altered the potential of mitochondrial membrane
NF-kB↓, Chrysin treatment in U937 cells (histiocytic lymphoma cells) showed induction of apoptosis by suppressing the PI3K/Akt signaling and inactivation of nuclear factor kappa B (NF-?B)/inhibitor of apoptosis (IAP)
p65↑,
MMP↓,
ROS↑, 25 to 100 μg/ml of Chinese propolis-treated cells showed increased ROS generation
MMP9↓, Cuban propolis (83 μg/ml) suppresses cell migration and invasion by inhibiting MMP-9 activity, β-catenin, vimentin expression, and decreased E-cadherin expression in human colorectal cancer
β-catenin/ZEB1↓,
Vim↓,
E-cadherin↓,
VEGF↓, Chinese red propolis and CAPE displayed a solid inhibitory effect in VEGF-mediated angiogenesis
EMT↓, Chinese propolis (12.5 μg/ml) inhibited Panc-1 cell migration by modulating the epithelial-mesenchymal transition

1675- PBG,    Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis
- in-vitro, Melanoma, A375 - in-vitro, Melanoma, WM983B
tumCV↓, fractions decreased cell viability
ROS↑, G18.EE and Its Fractions (n-BuOH and EtOAc) Promote Mitochondrial ROS Production in Melanoma Cells
antiOx↑, we can deduce that G18.EE may be a potential natural antioxidant value of EC50 (concentration that produces half of the maximal response) determined for the G18.EE was 10.90 ± 0.34 µg/mL
Apoptosis↑,
BAX↑, Both cell lines tested seem to display higher levels of Bax and p53, although not significant
P53↑,
Casp3↑, caspases 3 and 9 also appear to be enhanced by propolis treatments
Casp9↑,

1676- PBG,    Use of Stingless Bee Propolis and Geopropolis against Cancer—A Literature Review of Preclinical Studies
- Review, Var, NA
ROS↑, evidenced in the accumulation of reactive oxygen species (ROS)
MMP↓, reduction of mitochondrial membrane potential (Δψm)
Bcl-2↓, decreased levels of Bcl-2 proteins (antiapoptotic proteins) and AKT-3
eff↑, combination of the extract (30 µg/mL) with the antineoplastic vemurafenib (15 μM) against melanoma cells demonstrated a synergistic effect
tumCV↓, decreased cell viability for 23% of the colon cancer cells (SW620) treated with the aqueous propolis extract produced by Trigona laeviceps
TumCCA↑, antitumor activity of artepillin C is mediated by one of the following mechanisms: induction of cell cycle arrest in cancer cells, inhibition of angiogenesis, and inhibition of the oncogenic PAK1 signaling cascade
angioG↓,
PAK1↓,
HDAC1↓, negatively regulated expression of histone deacetylases (HDAC) 1 and 2
HDAC2↓,
P53↑, positive regulation of acetyl-p53 expression at the protein level
PCNA↓, negative regulation of cell-cycle-related gene expression, i.e., proliferating cell nuclear antigen (PCNA) and cyclin D1 and E1
cycD1↓,
cycE↓,
P21?, positively regulating the expression of the cell cycle arrest gene p21
BAX↑, Bax, Bcl-2, cleaved caspase-3, and poly(ADP-ribose) polymerase
cl‑Casp3↑,
cl‑PARP↑,
ChemoSen↑, apigenin significantly down-regulates Mcl-1 transcription and translation levels in SKOV3 and SKOV3/DDP cells, which is responsible for its cytotoxic functions and chemosensitizing effects

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↑, Selected Polyphenols Activate p53, PRODH/POX, Caspase 9 and 3 in CAL-27 Cell Line
Casp9↑,
Casp3↑,
GSH↓, chrysin (5 μg/mL), caffeic acid (65 μg/mL), ferulic acid (50 μg/mL), and p-coumaric acid (70 μg/mL). The obtained outcomes revealed a significant decrease in cellular GSH
proline↓, significant decrease in the intracellular proline concentration in case of CAL-27 cells treated with all studied polyphenols


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,3,   AMPK↑,1,   angioG↓,2,   angioG↑,1,   AntiCan↑,1,   antiOx↑,2,   Apoptosis↑,4,   BAX↑,7,   Bax:Bcl2↑,1,   Bcl-2↓,3,   Ca+2↑,1,   Casp↓,1,   Casp↑,2,   Casp3↑,5,   cl‑Casp3↑,1,   Casp9↑,2,   CDK4↑,1,   CDK6↑,1,   ChemoSen↑,5,   ChemoSideEff↓,1,   COX2↓,2,   CSCs↓,1,   cycD1↓,1,   cycE↓,1,   Cyt‑c↑,2,   DNAdam↑,2,   Dose?,1,   Dose↑,1,   Dose∅,2,   E-cadherin↓,1,   E-cadherin↑,1,   eff↓,1,   eff↑,10,   eff↝,2,   EGF↓,1,   EMT↓,2,   ERK↓,3,   ERK↑,1,   FAK↓,1,   Fas↓,1,   Fas↑,1,   Glycolysis↓,1,   GSH↓,1,   GSK‐3β↓,1,   HDAC1↓,1,   HDAC2↓,1,   Hif1a↓,1,   HK2↓,1,   IL1β↓,2,   IL1β↑,1,   IL6↓,2,   Inflam↓,1,   iNOS↓,2,   JNK↓,1,   LC3II↑,2,   LDH↓,1,   i-LDH↓,1,   LDHA↓,1,   MALAT1↓,1,   MAPK↓,2,   MAPK↑,1,   MMP↓,5,   MMP↝,1,   MMP2↓,1,   MMP9↓,2,   MMPs↓,1,   mtDam↑,1,   NDRG1↑,1,   NF-kB↓,6,   NF-kB↑,1,   OS↑,1,   P21?,1,   P21↑,1,   p27↑,1,   P53↑,8,   P53↝,1,   p62↓,2,   p65↑,1,   PAK1↓,1,   PARP↓,1,   cl‑PARP↑,1,   PCNA↓,1,   PFK↓,1,   PI3K↓,1,   PKM2↓,1,   proline↓,1,   RadioS↑,2,   RB1↑,1,   ROS↓,1,   ROS↑,8,   selectivity↑,2,   STAT3↓,1,   Telomerase↓,1,   TLR4↓,1,   TNF-α↓,3,   TRAIL↑,2,   TSP-1↑,1,   TumAuto↑,1,   TumCCA↓,1,   TumCCA↑,3,   TumCMig↓,2,   TumCP↓,3,   tumCV↓,3,   TumMeta↓,1,   VEGF↓,3,   Vim↓,2,   β-catenin/ZEB1↓,3,  
Total Targets: 107

Results for Effect on Normal Cells:
BioAv↓,1,  
Total Targets: 1

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
9 Propolis -bee glue
1 Caffeic acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:137  Target#:236  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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