Chrysin / TumCG 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.

Chrysin — Chrysin is a naturally occurring flavone-class flavonoid found in honey, propolis, passionflower, and several plants. Its oncology relevance is mainly preclinical: it shows multi-pathway anticancer activity in cell and animal models, but native oral chrysin has very poor systemic bioavailability and no established approved oncology use.

Primary mechanisms (ranked):

  1. Suppression of PI3K/AKT survival signaling with downstream reduction in proliferation and survival programs.
  2. Induction of mitochondrial apoptosis through Bax/Bcl-2 shift, mitochondrial membrane potential loss, cytochrome c release, and caspase activation.
  3. Context-dependent ROS stress amplification in cancer cells, often linked to mitochondrial injury, ER stress, and apoptosis.
  4. ER stress / unfolded-protein-response activation leading to autophagy or stress-to-death coupling.
  5. Suppression of inflammatory, invasive, angiogenic, and metastatic signaling including NF-κB, MMPs, EMT, VEGF, and HIF-1α axes.
  6. Secondary antioxidant / NRF2-linked cytoprotection in some normal-cell or injury models, which is context-dependent and not necessarily anticancer-selective.

Bioavailability / PK relevance: Native oral chrysin has very poor systemic exposure because of low aqueous solubility, extensive intestinal/hepatic glucuronidation and sulfation, and efflux; human oral bioavailability has been reported as extremely low, often summarized as below 1%. Formulation strategies such as nanoparticles, lipid systems, micelles, cyclodextrins, or structural analogues are commonly proposed for systemic translation.

In-vitro vs systemic exposure relevance: Most anticancer studies use micromolar in-vitro concentrations that are unlikely to be reached in plasma after ordinary oral chrysin. Local intestinal exposure may be more plausible than systemic tumor exposure, but systemic anticancer claims should be treated as formulation-dependent.
LipoMicel may increase bioavailability

Clinical evidence status: Preclinical. Evidence is strong enough for mechanistic oncology interest in cell and animal models, including combination/sensitization studies, but there is no mature clinical oncology evidence establishing therapeutic benefit.

-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

Chrysin Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 PI3K AKT survival signaling PI3K↓; AKT phosphorylation↓; survival signaling↓ ↔ R, G Growth and survival suppression Central hub mechanism reported across multiple tumor models; also supports chemosensitization.
2 Mitochondrial apoptosis MMP↓; Bax↑; Bcl-2↓; cytochrome c↑; caspase-9/3↑ ↔ or lower sensitivity R, G Intrinsic apoptosis execution One of the most consistent anticancer endpoints, usually downstream of stress and survival-pathway suppression.
3 Mitochondrial ROS stress ROS↑ (context-dependent); oxidative stress↑; lipid peroxidation↑ ROS↓ or antioxidant protection (context-dependent) P, R, G Stress amplification Direction is dose- and model-dependent; cancer models often show pro-oxidant stress, while normal injury models may show antioxidant behavior.
4 ER stress and UPR ER stress↑; GRP78↑; UPR↑; autophagy or apoptosis↑ ↔ R, G Stress-to-death coupling Important in several chrysin cancer models and in some drug-combination effects.
5 NF-κB inflammatory transcription NF-κB↓; COX-2↓; IL-6↓; TNF-α↓ Inflammatory injury signaling↓ R, G Anti-inflammatory and anti-survival signaling May contribute to reduced proliferation, invasion, and cytokine-driven tumor support.
6 Invasion EMT and MMPs EMT↓; MMP-2↓; MMP-9↓; uPA↓; migration↓; invasion↓ ↔ G Anti-invasive phenotype Mechanistically relevant for metastasis models but generally later and context-dependent.
7 Angiogenesis and HIF-1α VEGF signaling HIF-1α↓; VEGF↓; angiogenic output↓ ↔ G Anti-angiogenic support Reported in preclinical models; may overlap with oxidative stress and DNA damage response pathways.
8 Glycolysis and metabolic stress GLUT1↓; HK2↓; LDH↓; PDK1↓; lactate production↓; ATP↓ ↔ G Metabolic suppression Relevant but less central than apoptosis and survival signaling; strongest interpretation is model-dependent.
9 NRF2 antioxidant axis NRF2↓ or antioxidant defense↓ (model-dependent) NRF2↑; SOD↑; GSH↑; catalase↑ (context-dependent) R, G Context-dependent redox selectivity Potentially useful but also interpret carefully because NRF2 activation can be protective in normal cells and sometimes undesirable in cancer cells.
10 Chemosensitization and radiosensitization Drug-induced toxicity↑; apoptosis↑; resistance signaling↓ Chemoprotection reported in some injury models G Adjunct sensitization Promising preclinical adjunct signal, but not clinically established.
11 Clinical Translation Constraint Systemic exposure low after native oral dosing Dose and formulation constraints G Translation limitation Very poor oral bioavailability is the dominant practical constraint; formulation or local GI targeting is likely required.

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)
TumCG, Tumor cell growth: Click to Expand ⟱
Source:
Type:
Normal cells grow and divide in a regulated manner through the cell cycle, which consists of phases (G1, S, G2, and M).
Cancer cells often bypass these regulatory mechanisms, leading to uncontrolled proliferation. This can result from mutations in genes that control the cell cycle, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division).
Scientific Papers found: Click to Expand⟱
2800- CHr,    Chrysin Activates Notch1 Signaling and Suppresses Tumor Growth of Anaplastic Thyroid Carcinoma In vitro and In vivo
- in-vitro, Thyroid, NA
TumCG↓, Oral administration of chrysin suppressed the growth of ATC xenografts by an average of 59% compared with the vehicle control group
NOTCH↑, increase in the active intracellular domain of Notch1 protein
cl‑PARP↑, induction of cleaved Poly ADP-ribose polymerase protein, indicating that the growth inhibition was due to apoptosis.
Apoptosis↑,

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↓, chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo
GlucoseCon↓, Chrysin significantly reduced the levels of glycolytic indexes, such as glucose uptake
Casp3↑, hrysin dose-dependently increased the apoptotic rate and caspase 3/7 activity in KYSE410, KYSE30, and KYSE150 cells.
Casp7↑,
p‑Akt↓, chrysin dose-dependently inhibited the phosphorylation of AKT
TumCG↓, chrysin dose-dependently reduced the growth of ESCC tumors
Weight∅, difference of body weight between chrysin treatment groups and control group is minimal

6124- CHr,  EGCG,    The anticancer flavonoid chrysin induces the unfolded protein response in hepatoma cells
- in-vitro, HCC, HepG2
TumCG↓, report that chrysin inhibits hepatoma cells growth and induces apoptosis in a dose-dependent manner.
Apoptosis↓,
GRP78/BiP↑, Chrysin induces GRP78 overexpression, X-box binding protein-1 splicing and eukaryotic initiation factor 2α phosphorylation, hallmarks of the unfolded protein response.
eff↑, GRP78 knockdown potentiates chrysin-induced caspase-7 cleavage in hepatoma cells and enhances chrysin-induced apoptosis.
cl‑Casp7↑,
cl‑PARP↑, Combination of EGCG potentiates chrysin-induced caspase-7 and poly (ADP-ribose) polymerase (PARP) cleavage.
eff↑, Finally, EGCG sensitizes hepatoma cells to chrysin through caspase-mediated apoptosis
UPR↑, data suggest that chrysin triggers the unfolded protein response. Chrysin induces the unfolded protein response
ER Stress↑, Chrysin can induce ER stress response in hepatoma cells, including up-regulation of GRP78 expression, induction of eIF-2α phosphorylation and XBP-1 splicing.
p‑eIF2α↑,
XBP-1↝,
Proteasome↓, Chrysin is a known proteasome inhibitor [27]

1033- CHr,    Chrysin inhibits hepatocellular carcinoma progression through suppressing programmed death ligand 1 expression
- vitro+vivo, HCC, NA
TumCG↓,
CD4+↑, enhanced CD4/CD8-
CD8+↑, enhanced CD4/CD8-
PD-L1↓, chrysin significantly down-regulated the expression of PD-L1 in vivo and in vitro

2798- CHr,    Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of Chinese propolis
- in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
HDAC↓, chrysin is a histone deacetylase inhibitor (HDACi) and that it markedly inhibited HDAC8 enzymatic activity
HDAC8↓,
TumCG↓, chrysin significantly suppressed cell growth and induced differentiation in MDA-MB-231 cells
Diff↑,

2793- CHr,    Chrysin Inhibits TAMs-Mediated Autophagy Activation via CDK1/ULK1 Pathway and Reverses TAMs-Mediated Growth-Promoting Effects in Non-Small Cell Lung Cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H157 - in-vivo, NA, NA
TumCG↓, Chrysin displayed a significant inhibitory effect on the growth of NSCLC cells, and it could also suppress the pro-cancer effects of M2-TAMs and inhibit their mediated autophagy
M2 MC↑,
CDK1↓, Chrysin Inhibits Autophagy through the CDK1/ULK1 Pathway


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 1,   Casp3↑, 1,   Casp7↑, 1,   cl‑Casp7↑, 1,   Proteasome↓, 1,  

Protein Folding & ER Stress ⓘ

p‑eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,   XBP-1↝, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   HDAC↓, 1,   HDAC8↓, 1,   NOTCH↑, 1,   TumCG↓, 6,  

Migration ⓘ

FAK↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD4+↑, 1,   M2 MC↑, 1,   PD-L1↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 2,  

Clinical Biomarkers ⓘ

PD-L1↓, 1,  

Functional Outcomes ⓘ

Weight∅, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 28

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCG, Tumor cell growth
6 Chrysin
1 EGCG (Epigallocatechin Gallate)
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#:323  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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