Chrysin / Akt Cancer Research Results

CHr, Chrysin: Click to Expand ⟱
Features:
Chrysin is found in passion flower and honey. It is a flavonoid.
-To reach plasma levels that might more closely match the concentrations used in in vitro studies (typically micromolar), considerably high doses or advanced delivery mechanisms would be necessary.
Chrysin is widely summarized as modulating PI3K/Akt and MAPK pathways in cancer.

-Note half-life 2 hrs, BioAv very poor often <1%
Pathways:
Graphical Pathways

- may induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- May Lower AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ HO1↓
- May Raise AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, cMyc↓, GLUT1↓, LDH↓, HK2↓, PDKs↓, HK2↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, AMPK↓, ERK↓, JNK, TrxR,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, 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 PI3K → AKT (± mTOR) survival axis ↓ PI3K/AKT (often ↓ p-AKT; downstream growth signals ↓) ↔ R, G Growth/survival suppression Frequently reported hub effect; contributes to reduced proliferation and sensitization to stress/apoptosis programs.
2 Intrinsic apoptosis (p53/Bcl-2 family → caspase-9/3) ↑ p53 axis (context); Bax↑/Bcl-2↓; ↑ caspase-9/3; apoptosis ↑ ↔ (generally less activation) G Apoptosis execution Common endpoint across many tumor models; often downstream of survival-pathway suppression and stress signaling.
3 ER stress / UPR (PERK and related arms) ER stress ↑; UPR activation ↑ ↔ R, G Stress-to-death coupling ER stress has been directly shown in chrysin-treated cancer cells and can couple to apoptosis.
4 JAK / STAT3 signaling ↓ STAT3 signaling (context) ↔ R, G Anti-survival transcription STAT3 inhibition is reported in cancer models and often aligns with reduced proliferation and increased apoptosis.
5 ROS / oxidative stress (context-dependent) ROS modulation (often ↑ mitochondrial ROS in tumor models) ↔ / antioxidant behavior in some contexts P, R, G Stress amplifier (variable) Direction depends on dose/model; avoid absolute “ROS always ↑/↓”. Oxidative stress + DDR has been linked to anti-angiogenic effects in vivo in melanoma models.
6 MAPK re-wiring (ERK / JNK / p38) MAPK shifts; JNK/p38 often stress-activated; ERK variable ↔ P, R, G Signal reprogramming MAPK effects differ by cell line; chrysin can suppress JNK/ERK signaling to reduce MMP-9 in some models.
7 Cell-cycle arrest / proliferation control Cell-cycle arrest ↑; proliferation ↓ ↔ G Cytostasis Often observed as later phenotype-level outcomes, downstream of signaling changes.
8 Invasion / metastasis (MMP-9; EMT programs) MMP-9 ↓; migration/invasion ↓ (context) ↔ G Anti-invasive phenotype Chrysin can reduce MMP-9 expression via AP-1 suppression and MAPK pathway effects in certain cancer models.
9 Angiogenesis (VEGF/angiogenic outputs) Angiogenesis outputs ↓ (context) ↔ G Anti-angiogenic support In melanoma models, chrysin has been associated with angiogenesis regression linked to oxidative stress and DNA damage response.
10 Bioavailability constraint (oral PK limitation) Systemic exposure often low without formulation — — Translation constraint Native chrysin oral bioavailability is extremely low due to poor solubility and extensive glucuronidation/sulfation with efflux; formulation strategies are commonly required for systemic effects.

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

  • P: 0–30 min (primary/physical–chemical effects; rapid signaling / phosphorylation shifts)
  • R: 30 min–3 hr (acute stress-response and redox signaling)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
2792- CHr,    Chrysin induces death of prostate cancer cells by inducing ROS and ER stress
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
DNAdam↑, TumCCA↑, MMP↓, ROS↑, lipid-P↑, ER Stress↑, UPR↑, PERK↑, eIF2α↑, GRP78/BiP↑, PI3K↓, Akt↓, p70S6↓, MAPK↑,
2801- CHr,    AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells
- in-vitro, Lung, A549
AMPK↑, Akt↓, ChemoSen↑, ROS↑,
2805- CHr,    Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma (ESCC)
- in-vitro, ESCC, KYSE150 - in-vivo, ESCC, NA
FAK↓, GlucoseCon↓, Casp3↑, Casp7↑, p‑Akt↓, TumCG↓, Weight∅,
1145- CHr,    Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways
- in-vitro, Cerv, HeLa
tumCV↓, BAX↑, BID↑, BOK↑, APAF1↑, TNF-α↑, FasL↑, Fas↑, FADD↑, Casp3↑, Casp7↑, Casp8↑, Casp9↑, Mcl-1↓, NAIP↓, Bcl-2↓, CDK4↓, CycB/CCNB1↓, cycD1/CCND1↓, cycE1↓, TRAIL↑, p‑Akt↓, Akt↓, mTOR↓, PDK1↓, BAD↓, GSK‐3β↑, AMPK↑, p27↑, P53↑,
2780- CHr,    Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review
- Review, Var, NA
*antiOx↑, Inflam↓, *hepatoP↑, AntiCan↑, Cyt‑c↑, Casp3↑, XIAP↓, p‑Akt↓, PI3K↑, Apoptosis↑, COX2↓, FAK↓, AMPK↑, STAT3↑, MMP↓, DNAdam↑, BAX↑, Bak↑, Casp9↑, p38↑, MAPK↑, TumCCA↑, ChemoSen↑, HDAC8↓, Wnt↓, NF-kB↓, angioG↓, BioAv↓,
2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, MMP9↑, uPA↓, VEGF↓, AR↓, Casp↑, TumMeta↓, TumCCA↑, angioG↓, BioAv↓, *hepatoP↑, *neuroP↑, *SOD↑, *GPx↑, *ROS↓, *Inflam↓, *Catalase↑, *MDA↓, ROS↓, BBB↑, Half-Life↓, BioAv↑, ROS↑, eff↑, ROS↑, ROS↑, lipid-P↑, ER Stress↑, NOTCH1↑, NRF2↓, p‑FAK↓, Rho↓, PCNA↓, COX2↓, NF-kB↓, PDK1↓, PDK3↑, GLUT1↓, Glycolysis↓, mt-ATP↓, Ki-67↓, cMyc↓, ROCK1↓, TOP1↓, TNF-α↓, IL1β↓, CycB/CCNB1↓, CDK2↓, EMT↓, STAT3↓, PD-L1↓, IL2↑,
2782- CHr,    Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives
- Review, Var, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, *Inflam↓, *hepatoP↑, *neuroP↑, *BioAv↓, *cardioP↑, *lipidLev↓, *RenoP↑, *TNF-α↓, *IL2↓, *PI3K↓, *Akt↓, *ROS↓, *cognitive↑, eff↑, cycD1/CCND1↓, hTERT/TERT↓, VEGF↓, p‑STAT3↓, TumMeta↓, TumCP↓, eff↑, eff↑, IL1β↓, IL6↓, NF-kB↓, ROS↑, MMP↓, Cyt‑c↑, Apoptosis↑, ER Stress↑, Ca+2↑, TET1↑, Let-7↑, Twist↓, EMT↓, TumCCA↑, Casp3↑, Casp9↑, BAX↑, HK2↓, GlucoseCon↓, lactateProd↓, Glycolysis↓, SHP1↑, N-cadherin↓, E-cadherin↑, UPR↑, PERK↑, ATF4↑, eIF2α↑, RadioS↑, NOTCH1↑, NRF2↓, BioAv↑, eff↑,
2783- CHr,    Apoptotic Effects of Chrysin in Human Cancer Cell Lines
- Review, Var, NA
TumCP↓, Apoptosis↑, Casp↑, PCNA↓, p38↑, NF-kB↑, DNAdam↑, XIAP↓, Cyt‑c↑, Casp3↑, Akt↓, SCF↓, hTERT/TERT↓, COX2↓, *Inflam↓, *antiOx↑, *chemoPv↑, AR-V7?, CYP19?,
2785- CHr,    Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin
- Review, Var, NA
*NF-kB↓, *COX2↓, *iNOS↓, angioG↓, TOP1↓, HDAC↓, TNF-α↓, IL1β↓, cardioP↑, RenoP↑, neuroP↑, LDL↓, BioAv↑, eff↑, cycD1/CCND1↓, hTERT/TERT↓, MMP-10↓, Akt↓, STAT3↓, VEGF↓, EGFR↓, Snail↓, Slug↓, Vim↓, E-cadherin↑, eff↑, TET1↑, ROS↑, mTOR↓, PPARα↓, ER Stress↑, Ca+2↑, ERK↓, MMP↑, Cyt‑c↑, Casp3↑, HK2↓, NRF2↓, HO-1↓, MMP2↓, MMP9↓, Fibronectin↓, GRP78/BiP↑, XBP-1↓, p‑eIF2α↑, *AST↓, ALAT↓, ALP↓, LDH↓, COX2↑, Bcl-xL↓, IL6↓, PGE2↓, iNOS↓, DNAdam↑, UPR↑, Hif1a↓, EMT↓, Twist↓, lipid-P↑, CLDN1↓, PDK1↓, IL10↓, TLR4↓, NOTCH1↑, PARP↑, Mcl-1↓, XIAP↓,
2786- CHr,    Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives
- Review, Var, NA
Apoptosis↑, TumCCA↑, angioG↓, TumCI↓, TumMeta↑, *toxicity↓, selectivity↑, chemoPv↑, *GSTs↑, *NADPH↑, *GSH↑, HDAC8↓, Hif1a↓, *ROS↓, *NF-kB↓, SCF↓, cl‑PARP↑, survivin↓, XIAP↓, Casp3↑, Casp9↑, GSH↓, ChemoSen↑, Fenton↑, P21↑, P53↑, cycD1/CCND1↓, CDK2↓, STAT3↓, VEGF↓, Akt↓, NRF2↓,
2787- CHr,    Network pharmacology unveils the intricate molecular landscape of Chrysin in breast cancer therapeutics
- Analysis, Var, MCF-7
TumCP↓, angioG↓, TumCI↓, TumMeta↓, TP53↑, Akt↓, Casp3↑, tumCV↓, TNF-α↓, BioAv↑, BioAv↑, AKT1↓,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Fenton↑, 1,   GSH↓, 1,   HO-1↓, 1,   lipid-P↑, 3,   NRF2↓, 4,   ROS↓, 1,   ROS↑, 7,  

Mitochondria & Bioenergetics ⓘ

mt-ATP↓, 1,   BOK↑, 1,   MMP↓, 3,   MMP↑, 1,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   ALAT↓, 1,   AMPK↑, 3,   cMyc↓, 1,   GlucoseCon↓, 2,   Glycolysis↓, 2,   HK2↓, 2,   lactateProd↓, 1,   LDH↓, 1,   LDL↓, 1,   PDK1↓, 3,   PDK3↑, 1,   PPARα↓, 1,  

Cell Death ⓘ

Akt↓, 8,   p‑Akt↓, 3,   APAF1↑, 1,   Apoptosis↑, 4,   BAD↓, 1,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 1,   Bcl-xL↓, 1,   BID↑, 1,   Casp↑, 2,   Casp3↑, 8,   Casp7↑, 2,   Casp8↑, 1,   Casp9↑, 4,   Cyt‑c↑, 4,   FADD↑, 1,   Fas↑, 1,   FasL↑, 1,   hTERT/TERT↓, 3,   iNOS↓, 1,   MAPK↑, 2,   Mcl-1↓, 2,   NAIP↓, 1,   p27↑, 1,   p38↑, 2,   survivin↓, 1,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 2,   p‑eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 2,   PERK↑, 2,   UPR↑, 3,   XBP-1↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 1,   PCNA↓, 2,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 4,   cycE1↓, 1,   P21↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

AR-V7?, 1,   EMT↓, 3,   ERK↓, 1,   GSK‐3β↑, 1,   HDAC↓, 1,   HDAC8↓, 2,   Let-7↑, 1,   mTOR↓, 3,   NOTCH1↑, 3,   PI3K↓, 2,   PI3K↑, 1,   SCF↓, 2,   SHP1↑, 1,   STAT3↓, 3,   STAT3↑, 1,   p‑STAT3↓, 1,   TOP1↓, 2,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

Ca+2↑, 2,   CLDN1↓, 1,   E-cadherin↑, 2,   FAK↓, 2,   p‑FAK↓, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP-10↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMP9↑, 1,   N-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   Slug↓, 1,   Snail↓, 1,   TET1↑, 2,   TumCI↓, 2,   TumCP↓, 3,   TumMeta↓, 3,   TumMeta↑, 1,   Twist↓, 2,   uPA↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   ATF4↑, 1,   EGFR↓, 1,   Hif1a↓, 2,   VEGF↓, 4,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   COX2↑, 1,   IL10↓, 1,   IL1β↓, 3,   IL2↑, 1,   IL6↓, 2,   Inflam↓, 1,   NF-kB↓, 3,   NF-kB↑, 1,   PD-L1↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 3,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CYP19?, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 5,   ChemoSen↑, 3,   eff↑, 7,   Half-Life↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AR↓, 1,   EGFR↓, 1,   hTERT/TERT↓, 3,   IL6↓, 2,   Ki-67↓, 1,   LDH↓, 1,   PD-L1↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoPv↑, 1,   neuroP↑, 1,   RenoP↑, 1,   Weight∅, 1,  
Total Targets: 164

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   MDA↓, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

lipidLev↓, 1,   NADPH↑, 1,  

Cell Death ⓘ

Akt↓, 1,   iNOS↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL2↓, 1,   Inflam↓, 3,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

AST↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoPv↑, 1,   cognitive↑, 1,   hepatoP↑, 3,   neuroP↑, 2,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 27

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
11 Chrysin
1 Propolis -bee glue
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#:61  Target#:4  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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