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


CDK2, Cyclin-dependent kinase 2: Click to Expand ⟱
Source:
Type:
(CDK2) complex is significantly over-activated in many cancers.
CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation.
Scientific Papers found: Click to Expand⟱
2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

3256- PBG,    Mechanisms of Apoptosis and Cell Cycle Arrest Induced by Propolis in Cancer Therapy
- Review, Var, NA
TumCCA↑, The flavonoids and phenolic acids in propolis also play critical roles in halting cell proliferation by arresting the cell cycle at G0/G1 or G2/M phases, often through the downregulation of cyclins and cyclin-dependent kinases (CDKs).
CDK2↓, CAPE attenuates CDK2/4 activity through Akt–Skp2 signalling in CRPC cells
CDK4↓,
cycA1↓, Whole-extract propolis lowered cyclin A and B1 in U-937 leukaemia cells
CycB↓,

1666- PBG,    Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer
- Review, Var, NA
ChemoSen↑, Ingredients from propolis also ”sensitize“ cancer cells to chemotherapeutic agents
TumCCA↑, cell-cycle arrest and attenuation of cancer cells proliferation
TumCP↓,
Apoptosis↑,
antiOx↓, behave as antioxidants against peroxyl and hydroxyl radicals,
ROS↑, whereas prooxidant activity is observed in the presence of Cu2+.
COX2↑, Propolis, as well as flavonoids derived from propolis, such as galangin, is a potent COX-2 inhibitor
ER(estro)↓, Some flavonoids from propolis, such as galangin, genistein, baicalein, hesperetin, naringenin, and quercetin, suppressed the proliferation of an estrogen receptor (ER)
cycA1↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
CycB↓,
CDK2↓,
P21↑,
p27↑,
hTERT↓, leukemia cells, propolis successfully reduced hTERT mRNA expression
HDAC↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
ROS⇅, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
Dose?, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
ROS↓, By scavenging free radicals, chelating metal ions (mainly iron and copper), and stimulating endogenous antioxidant defenses, propolis and its flavonoids directly attenuate the generation of ROS
ROS↑, Romanian propolis [99], exhibits prooxidant properties at high concentrations, by mobilizing endogenous copper ions and DNA-associated copper in cells.
DNAdam↑, propolis, i.e., its polyphenolic components, may induce DNA damage in the presence of transition metal ions.
ChemoSen↑, Algerian propolis + doxorubicin decreased cell viability, prevented cell proliferation and cell cycle progression, induced apoptosis by activating caspase-3 and -9 activities, and increased the accumulation of chemotherapeutic drugs in MDA-MB-231 cel
LOX1↓, propolis components inhibited the LOX pathway
lipid-P↓, Croatian propolis improved psoriatic-like skin lesions induced by irritant agents n-hexyl salicylate or di-n-propyl disulfide by decreasing the extent of lipid peroxidation
NO↑, Taken together, propolis may increase the phagocytic index, NO production, and production of IgG antibodies
Igs↑,
NK cell↑, propolis treatment for 3 days increases the cytotoxic activity of NK cells against murine lymphoma.
MMPs↓, extracts of propolis containing artepillin C and CAPE decreased the formation of new vessels and expression of MMPs and VEGF in various cancer cells
VEGF↓,
Hif1a↓, Brazilian green propolis inhibit the expression of the hypoxia-inducible factor-1 (HIF-1) protein and HIF-1 downstream targets such as glucose transporter 1, hexokinase 2, and VEGF-A
GLUT1↓,
HK2↓,
selectivity↑, Portuguese propolis was selectively toxic against malignant cells.
RadioS↑, propolis increased the lifespan of mice that received the radiotherapy with gamma rays
GlucoseCon↓, Portuguese propolis disturbed the glycolytic metabolism of human colorectal cancer cells, as evidenced by a decrease in glucose consumption and lactate production
lactateProd↓,
eff↓, Furthermore, different pesticides or heavy metals can be found in propolis, which can cause unwanted side effects.
*BioAv↓, Due to the low bioavailability and clinical efficacy of propolis and its flavonoids, their biomedical applications remain limited.


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

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   antiOx↓,1,   Apoptosis↑,1,   AR↓,1,   mt-ATP↓,1,   BBB↑,1,   BioAv↓,1,   BioAv↑,1,   Casp↑,1,   CDK2↓,3,   CDK4↓,1,   ChemoSen↑,2,   cMyc↓,1,   COX2↓,1,   COX2↑,1,   cycA1↓,2,   CycB↓,3,   DNAdam↑,1,   Dose?,1,   eff↓,1,   eff↑,1,   EMT↓,1,   ER Stress↑,1,   ER(estro)↓,1,   p‑FAK↓,1,   GlucoseCon↓,1,   GLUT1↓,2,   Glycolysis↓,1,   Half-Life↓,1,   HDAC↓,1,   Hif1a↓,1,   HK2↓,1,   hTERT↓,1,   Igs↑,1,   IL1β↓,1,   IL2↑,1,   Ki-67↓,1,   lactateProd↓,1,   lipid-P↓,1,   lipid-P↑,1,   LOX1↓,1,   MMP9↑,1,   MMPs↓,1,   mTOR↓,1,   NF-kB↓,1,   NK cell↑,1,   NO↑,1,   NOTCH1↑,1,   NRF2↓,1,   P21↑,1,   p27↑,1,   PCNA↓,1,   PD-L1↓,1,   PDK1↓,1,   PDK3↑,1,   PI3K↓,1,   RadioS↑,1,   Rho↓,1,   ROCK1↓,1,   ROS↓,2,   ROS↑,5,   ROS⇅,1,   selectivity↑,1,   STAT3↓,1,   TNF-α↓,1,   TOP1↓,1,   TumCCA↑,3,   TumCP↓,1,   TumMeta↓,1,   uPA↓,1,   VEGF↓,2,  
Total Targets: 72

Results for Effect on Normal Cells:
BioAv↓,1,   Catalase↑,1,   GPx↑,1,   hepatoP↑,1,   Inflam↓,1,   MDA↓,1,   neuroP↑,1,   ROS↓,1,   SOD↑,1,  
Total Targets: 9

Scientific Paper Hit Count for: CDK2, Cyclin-dependent kinase 2
3 Propolis -bee glue
1 Chrysin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:137  Target#:467  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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