Chrysin / CYP19 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)
CYP19, aromatase: Click to Expand ⟱
Source:
Type:
CYP19, also known as aromatase, is an enzyme that plays a crucial role in the biosynthesis of estrogens by converting androgens (such as testosterone and androstenedione) into estrogens (such as estradiol and estrone). The activity of CYP19 is significant in various tissues, including the ovaries, testes, adipose tissue, and the brain.

-Estrogen Production: Elevated levels of estrogens, which can result from increased CYP19 activity, are associated with the development and progression of certain cancers, particularly estrogen receptor--positive breast cancer.
-Aromatase Inhibitors: In the treatment of hormone-sensitive breast cancer, aromatase inhibitors (such as anastrozole, letrozole, and exemestane) are commonly used. These drugs work by inhibiting the activity of CYP19, thereby reducing estrogen levels and slowing the growth of estrogen-dependent tumors.
Scientific Papers found: Click to Expand⟱
6133- CHr,    Chrysin in PI3K/AKT and other apoptosis signalling pathways, and its effect on HeLa cells.
- Review, Var, NA
TumCP↓, chrysin inhibits proliferation, induces apoptosis and reduce angiogenesis in most tested cancer cells, including cervical cancer cells.
Apoptosis↑,
angioG↓,
eff↑, biological activities of chrysin may be improved by modification of the original structure of chrysin or combination therapy.
CYP19↓, Chrysin is also reported as a potent inhibitor of aromatase which is responsible for blocking the conversion of androgen to estrogens
Hif1a↓, Chrysin suppresses HIF-1α/VEGF and angiogenesis
VEGF↓,
NF-kB↓, Chrysin downregulates NFκB and its target genes
PI3K↓, Chrysin inactivates PI3K/AKT signalling pathway in apoptosis
Akt↓,

2783- CHr,    Apoptotic Effects of Chrysin in Human Cancer Cell Lines
- Review, Var, NA
TumCP↓, chrysin has shown to inhibit proliferation and induce apoptosis, and is more potent than other tested flavonoids in leukemia cells
Apoptosis↑,
Casp↑, chrysin is likely to act via activation of caspases and inactivation of Akt signaling in the cells.
PCNA↓, inhibited the growth of cervical cancer cells, HeLa, via apoptosis induction and down-regulated the proliferating cell nuclear antigen (PCNA) in the cells.
p38↑, chrysin potentially induced p38, therefore activated NFkappaB/p65 in the HeLa cells
NF-kB↑,
DNAdam↑, only apigenin, chrysin, quercetin, galangin, luteolin and fisetin were found to clearly induce the oligonucleosomal DNA fragmentation at 50 μM after 6 h of treatment
XIAP↓, down-regulation of X-linked inhibitor of apoptosis protein (XIAP) in the U937 cells
Cyt‑c↑, (1) chrysin mediated the release of cytochrome c from mitochondria into the cytoplasm;
Casp3↑, (2) chrysin induced elevated caspase-3 activity and proteolytic cleavage of its downstream targets, such as phospholipase C-gamma-1 (PLC-gamma1), which is correlated with down-regulation of XIAP;
Akt↓, (3) chrysin decreased phosphorylated Akt levels in cells where the PI3K pathway plays a role in regulating the mechanism.
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling by inhibiting the PI3K pathway
hTERT/TERT↓, A significant decrease in human telomerase reverse transcriptase (hTERT) expression levels was also observed in leukemia cells treated with 60 ng/mL Manisa propolis, owing to its constituent of chrysin
COX2↓, Chrysin also inhibited the lipopolysaccharide-induced COX-2 expression via inhibition of nuclear factor IL-6 (NF-IL6)
*Inflam↓, anti-inflammatory [21] and anti-oxidant effects [22], and has shown cancer chemopreventive activity via induction of apoptosis in diverse range of human and rat cell types.
*antiOx↑,
*chemoPv↑,
AR-V7?,
CYP19?, Chrysin has recently shown to be a potent inhibitor of aromatase [18] and of human immunodeficiency virus activation in models of latent infection


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics(tgid=3) ⓘ

XIAP↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↑, 2,   Casp↑, 1,   Casp3↑, 1,   Cyt‑c↑, 1,   hTERT/TERT↓, 1,   p38↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   PCNA↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

AR-V7?, 1,   PI3K↓, 1,   SCF↓, 1,  

Migration(tgid=13) ⓘ

TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   NF-kB↓, 1,   NF-kB↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CYP19?, 1,   CYP19↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

hTERT/TERT↓, 1,  
Total Targets: 24

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: CYP19, aromatase
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#:75  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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