Chrysin / selectivity 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)
selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
Scientific Papers found: Click to Expand⟱
6126- CHr,    Chrysin induces cell apoptosis in human uveal melanoma cells via intrinsic apoptosis
- in-vitro, Melanoma, NA
tumCV↓, Chrysin reduced the viability of cultured human melanoma cells in a dose-dependent manner (0, 10, 30 and 100 µM) with IC50 at 28.3 and 35.8 µM
selectivity↑, Chrysin at 30–100 µM levels selectively reduced the viability of melanoma cells without affecting the viability of scleral fibroblasts and RPE cells.
MPT↑, Chrysin increased mitochondrial permeability, the levels of cytosol cytochrome c, and caspase-9 and −3 activities, but not capase-8 activity in uveal melanoma cells.
Cyt‑c↑,
Casp3↑,
Casp9↑,
Apoptosis↑, induces apoptosis of human uveal melanoma cells via the mitochondrial signaling pathway
mtDam↑,
chemoPv↑, Chrysin has been demonstrated to possess cancer chemopreventive activity through inhibition of cell proliferation (10,18), and induce apoptosis in various malignant cancer cells

2806- CHr,  Se,    Selenium-containing chrysin and quercetin derivatives: attractive scaffolds for cancer therapy
- in-vitro, Var, NA
eff↑, SeChry elicited a noteworthy cytotoxic activity with mean IC50 values 18- and 3-fold lower than those observed for chrysin and cisplatin, respectively
selectivity↑, differential behavior toward malignant and nonmalignant cells was observed for SeChry and SePQue, exhibiting higher selectivity indexes
Dose↝, 5 min. of microwave irradiation at 175 W (150 ºC) of an acetonitrile WR and flavonoid solution on a sealed pyrex microwave vial,
TrxR↓, Both compounds were able to decrease cellular TrxR
GSH↓, The results clearly showed that after treatment with both seleno-flavonoids total glutathione concentration (GSH + GSSG) decreased
MMP↓, MMP reduced by up to four times compared to control cells
ROS↑, Both seleno-derivatives were able to increase the oxidant basal production
H2O2↑, ore dramatic decrease of the MMP and a higher ability to increase the hydrogen peroxide basal production,

6132- CHr,  MET,    Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression
- in-vitro, BC, T47D
eff↑, combination of metformin and chrysin had high synergistic effects in killing cancer cells
cycD1/CCND1↓, significant decrease in cyclin D1 and hTERT gene expression in the T47D breast cancer cell line.
hTERT/TERT↓,
TumCP↓, in vivo studies have revealed that Chrysin suppresses cancer cell proliferation via apoptosis induction, cell cycle alteration, microRNA modulation and inhibition of invasion, metastasis and angiogenesis
Apoptosis↑,
TumCI↓,
TumMeta↓,
angioG↓,
selectivity↑, without triggering undesirable side effects and toxicity to normal cells

6139- CHr,    Chrysin and its nanoformulations in cancer therapy: A systematic review of their radiosensitizing, phototherapy-enhancing potentials
- Review, Var, NA
RadioS↑, CHY and its NPs, when combined with radiotherapy (RT) and phototherapy(PT), generate singlet oxygen (¹O₂) and various reactive oxygen species (ROS), causing photooxidative damage, DNA injury, cell-cycle arrest often at the G1 phase, and apoptotic ce
PhotoS↑,
ROS↑,
DNAdam↑,
TumCCA↑,
TumCD↑,
selectivity↑, Conversely, CHY shows notable protective effects in normal cells by reducing oxidative stress, neuroinflammation, and DNA damage through restoring antioxidant defenses, lowering lipid peroxidation, and maintaining neuronal integrity
*ROS↓,
*Inflam↓,
*DNAdam↓,
*antiOx↑,
*lipid-P↓,
*BioAv↑, new developments in CHY-based nanocarrier systems that enhance bioavailability and treatment accuracy, providing a focused view not found in previous reviews of CHY or flavonoids.
eff↑, CHY-derived copper NPs (CuNPs) enhanced the effects of low-dose γ-irradiation in Swiss albino mice bearing Ehrlich tumors and in MCF-7 breast cancer cells
GSH↓, Combined treatment reduced GSH, catalase (CAT), alanine aminotransferase (ALT), creatinine (Cr), and Ca²⁺ levels while increasing MDA levels, indicating intensified oxidative stress
Catalase↓,
ALAT↓,
Ca+2↓,
MDA↑,

2784- CHr,    Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)
- Review, Var, NA
Apoptosis↑, apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side‑effects in normal cells
TumCMig↓,
*toxicity↝, toxic at higher doses and the recommended dose for chrysin is <3 g/day
ChemoSen↑, chrysin also inhibits multi‑drug resistant proteins and is effective in combination therapy
*BioAv↓, extremely low bioavailability in humans due to rapid quick metabolism, removal and restricted assimilation. The bioavailability of chrysin when taken orally has been estimated to be between 0.003 to 0.02%
Dose↝, safe and effective in various studies where volunteers have taken oral doses ranging from 300 to 625 mg without experiencing any documented effect
neuroP↑, Chrysin has been shown to exert neuroprotective effects via a variety of mechanisms, such as gamma-aminobutyric acid mimetic properties, monoamine oxidase inhibition, antioxidant, anti-inflammatory and anti-apoptotic activities
*P450↓, Chrysin inhibits cytochrome P450 2E1, alcohol dehydrogenase and xanthine oxidase at various dosages (20 and 40 mg/kg body weight) and protects Wistar rats against oxidative stress
*ROS↓,
*HDL↑, ncreased the levels of high-density lipoprotein cholesterol, glutathione S-transferase, superoxide dismutase and catalase
*GSTs↑,
*SOD↑,
*Catalase↑,
*MAPK↓, inactivate the MAPK/JNK pathway and suppress the NF-κB pathways, and at the same time upregulate the expression of PTEN, and activate the VEGF/AKT pathway
*NF-kB↓,
*PTEN↑,
*VEGF↑,
ROS↑, chrysin treatment in ovarian cancer led to the augmented generation of reactive oxygen species, a decrease in MMP and an increase in cytoplasmic Ca2+,
MMP↓,
Ca+2↑,
selectivity↑, It has been found that chrysin has no cytotoxic effect on normal cells, such as fibroblasts
PCNA↓, Chrysin likewise downregulates proliferating cell nuclear antigen (PCNA) expression in cervical carcinoma cells
Twist↓, Chrysin decreases the expression of TWIST 1 and NF-κB and thus suppresses epithelial-mesenchymal transition (EMT) in HeLa cells
EMT↓,
CDKN1C↑, Chrysin administration led to the upregulation of CDKN1 at the transcript and protein leve
p‑STAT3↑, Chrysin decreased the viability of 4T1 breast cancer cells by suppressing hypoxia-induced phosphorylation of STAT3
MMP2↓, chrysin-loaded PGLA/PEG nanoparticles modulated TIMPS and MMP2 and 9, and PI3K expression in a mouse 4T1 breast tumor model
MMP9↓,
eff↑, Chrysin used alone and as an adjuvant with metformin has been found to downregulate cyclin D and hTERT expression in the breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
CLDN1↓, CLDN1 and CLDN11 expression have been found to be higher in human lung squamous cell carcinoma. Treatment with chrysin treatment reduces both the mRNA and protein expression of these claudin genes
TumVol↓, Treatment with chrysin treatment (1.3 mg/kg body weight) significantly decreases tumor volume, resulting in a 52.6% increase in mouse survival
OS↑,
COX2↓, Chrysin restores the cellular equilibrium of cells subjected to benzopyrene by downregulating the expression of elevated proteins, such as PCNA, NF-κB and COX-2
eff↑, quercetin and chrysin together decreased the levels of pro-inflammatory molecules, such as IL-6, -1 and -10, and the levels of TNF via the NF-κB pathway.
CDK2↓, Chrysin has been shown to inhibit squamous cell carcinoma via the modulation of Rb and by decreasing the expression of CDK2 and CDK4
CDK4↓,
selectivity↑, chrysin selectively exhibits toxicity and induces the self-programed death of human uveal melanoma cells (M17 and SP6.5) without having any effect on normal cells
TumCCA↑, halting the cell cycle at the G2/M or G1/S phases
E-cadherin↑, upregulation of E-cadherin and the downregulation of cadherin
HK2↓, Chrysin decreased expression of HK-2 in mitochondria, and the interaction between HK-2 and VDAC 2 was disrupted,
HDAC↓, Chrysin, a HDAC inhibitor, caused cytotoxicity, and also inhibited migration and invasion.

2786- CHr,    Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives
- Review, Var, NA
Apoptosis↑, chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells
TumCCA↑,
angioG↓,
TumCI↓,
TumMeta↑,
*toxicity↓,
selectivity↑,
chemoPv↑, Induction of phase II detoxification enzymes, such as glutathione S-transferase (GST) or NAD(P)H:quinone oxidoreductase (QR) is one of the major mechanism of protection against initiation of carcinogenesis
*GSTs↑,
*NADPH↑,
*GSH↑, upregulation of antioxidant and carcinogen detoxification enzymes (glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), GST and QR)
HDAC8↓, inhibits of HDAC8 enzymatic activity
Hif1a↓, Prostate DU145: Inhibits HIF-1a expression through Akt signaling and abrogation of VEGF expression
*ROS↓, chrysin (20 and 40 mg/kg) was shown to exhibit chemopreventive activity by ameliorating oxidative stress and inflammation via NF-kB pathway
*NF-kB↓,
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling in human myeloid leukemia cells by preventing the PI3 K pathway
cl‑PARP↑, (PARP) and caspase-3 and concurrently decreasing pro-survival proteins survivin and XIAP
survivin↓,
XIAP↓,
Casp3↑, activation of caspase-3 and -9.
Casp9↑,
GSH↓, chrysin sustains a significant depletion of intracellular GSH concentrations in human NSCLC cells
ChemoSen↑, chrysin potentiates cisplatin toxicity, in part, via synergizing pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and by depleting cellular GSH, an important antioxidant defense
Fenton↑, ability to participate in a fenton type chemical reaction
P21↑, upregulation of p21 independent of p53 status and decrease in cyclin D1, CDK2 protein levels
P53↑,
cycD1/CCND1↓,
CDK2↓,
STAT3↓, chrysin inhibits angiogenesis through inhibition of STAT3 and VEGF release mediated by hypoxia through Akt signaling pathway
VEGF↓,
Akt↓,
NRF2↓, Chrysin treatment significantly reduced nrf2 expression in cells at both the mRNA and protein levels through down-regulation of PI3K-Akt and ERK pathways.


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:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   Fenton↑, 1,   GSH↓, 3,   H2O2↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 3,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   MPT↑, 1,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   HK2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 4,   Casp3↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   hTERT/TERT↓, 2,   survivin↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

PhotoS↑, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 1,   cycD1/CCND1↓, 3,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   HDAC↓, 1,   HDAC8↓, 1,   SCF↓, 1,   STAT3↓, 1,   p‑STAT3↑, 1,  

Migration ⓘ

Ca+2↓, 1,   Ca+2↑, 1,   CDKN1C↑, 1,   CLDN1↓, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   TumMeta↑, 1,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose↝, 2,   eff↑, 5,   RadioS↑, 1,   selectivity↑, 7,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   hTERT/TERT↓, 2,  

Functional Outcomes ⓘ

chemoPv↑, 2,   neuroP↑, 1,   OS↑, 1,   TumVol↓, 1,  
Total Targets: 67

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↑, 1,   GSTs↑, 2,   HDL↑, 1,   lipid-P↓, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↑, 1,  

Cell Death ⓘ

MAPK↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

PTEN↑, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   P450↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 20

Scientific Paper Hit Count for: selectivity, selectivity
6 Chrysin
1 Selenium
1 Metformin
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#:1110  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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