Chrysin / MMP 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↓">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)
MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱
Source:
Type:
Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.


Scientific Papers found: Click to Expand⟱
2790- CHr,    Chrysin: Pharmacological and therapeutic properties
- Review, Var, NA
*hepatoP↑, *neuroP↓, *ROS↓, *cardioP↑, *Inflam↓, eff↑, hTERT/TERT↓, cycD1/CCND1↓, MMP9↓, MMP2↓, TIMP1↑, TIMP2↑, BioAv↑, HK2↓, ROS↑, MMP↓, Casp3↑, ADP:ATP↑, Apoptosis↑, ER Stress↑, UPR↑, GRP78/BiP↝, eff↑, Ca+2↑,
2791- CHr,    Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction
- in-vitro, Ovarian, OV90
TumCP↓, TumCD↑, ROS↑, Ca+2↑, MMP↓, MAPK↑, PI3K↑, p‑Akt↑, PCNA↓, p‑p70S6↑, p‑ERK↑, p38↑, JNK↑, DNAdam↑, TumCCA↑, chemoP↑,
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↑,
2804- CHr,  Rad,    Gamma-Irradiated Chrysin Improves Anticancer Activity in HT-29 Colon Cancer Cells Through Mitochondria-Related Pathway
- in-vitro, CRC, HT29
RadioS↑, ROS↑, MMP↓, Casp3↑, Casp9↑, cl‑PARP↑,
2806- CHr,  Se,    Selenium-containing chrysin and quercetin derivatives: attractive scaffolds for cancer therapy
- in-vitro, Var, NA
eff↑, selectivity↑, Dose↝, TrxR↓, GSH↓, MMP↓, ROS↑, H2O2↑,
1249- CHr,    Chrysin as an Anti-Cancer Agent Exerts Selective Toxicity by Directly Inhibiting Mitochondrial Complex II and V in CLL B-lymphocytes
- in-vitro, CLL, NA
ROS↑, MMP↓, ADP:ATP↑, Casp3↑, Apoptosis↑,
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↓,
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↑,
2784- CHr,    Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)
- Review, Var, NA
Apoptosis↑, TumCMig↓, *toxicity↝, ChemoSen↑, *BioAv↓, Dose↝, neuroP↑, *P450↓, *ROS↓, *HDL↑, *GSTs↑, *SOD↑, *Catalase↑, *MAPK↓, *NF-kB↓, *PTEN↑, *VEGF↑, ROS↑, MMP↓, Ca+2↑, selectivity↑, PCNA↓, Twist↓, EMT↓, CDKN1C↑, p‑STAT3↑, MMP2↓, MMP9↓, eff↑, cycD1/CCND1↓, hTERT/TERT↓, CLDN1↓, TumVol↓, OS↑, COX2↓, eff↑, CDK2↓, CDK4↓, selectivity↑, TumCCA↑, E-cadherin↑, HK2↓, HDAC↓,
481- CUR,  CHr,  Api,    Flavonoid-induced glutathione depletion: Potential implications for cancer treatment
- in-vitro, Liver, A549 - in-vitro, Pca, PC3 - in-vitro, AML, HL-60
GSH↓, mtDam↑, MMP↓, Cyt‑c↑,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 2,   H2O2↑, 1,   lipid-P↑, 1,   NRF2↓, 1,   ROS↑, 8,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 2,   MMP↓, 10,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 3,   lactateProd↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   p‑Akt↑, 1,   Apoptosis↑, 5,   Bak↑, 1,   BAX↑, 2,   Casp3↑, 5,   Casp9↑, 3,   Cyt‑c↑, 3,   hTERT/TERT↓, 3,   JNK↑, 1,   MAPK↑, 3,   p38↑, 2,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,   p‑p70S6↑, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 2,   ER Stress↑, 3,   GRP78/BiP↑, 1,   GRP78/BiP↝, 1,   PERK↑, 2,   UPR↑, 3,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   cl‑PARP↑, 1,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 3,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   p‑ERK↑, 1,   HDAC↓, 1,   HDAC8↓, 1,   Let-7↑, 1,   NOTCH1↑, 1,   PI3K↓, 1,   PI3K↑, 2,   SHP1↑, 1,   STAT3↑, 1,   p‑STAT3↓, 1,   p‑STAT3↑, 1,   Wnt↓, 1,  

Migration ⓘ

Ca+2↑, 4,   CDKN1C↑, 1,   CLDN1↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   TET1↑, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 2,   Dose↝, 2,   eff↑, 9,   RadioS↑, 2,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 3,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 1,   neuroP↑, 1,   OS↑, 1,   TumVol↓, 1,  
Total Targets: 94

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSTs↑, 1,   HDL↑, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

lipidLev↓, 1,  

Cell Death ⓘ

Akt↓, 1,   MAPK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   PTEN↑, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↑, 1,  

Immune & Inflammatory Signaling ⓘ

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

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   P450↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 3,   neuroP↓, 1,   neuroP↑, 1,   RenoP↑, 1,   toxicity↝, 1,  
Total Targets: 25

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential
10 Chrysin
1 Radiotherapy/Radiation
1 Selenium
1 Curcumin
1 Apigenin (mainly Parsley)
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#:197  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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