Database Query Results : Chrysin, , ChemoSen

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)

ChemoSen, chemo-sensitization: Click to Expand ⟱

Source:

Type:

The effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”.

Chemo-Sensitizers:
-Curcumin
-Resveratrol
-EGCG
-Quercetin
-Genistein
-Berberine
-Piperine: alkaloid from black pepper
-Ginsenosides: active components of ginseng
-Silymarin
-Allicin
-Lycopene
-Ellagic acid
-caffeic acid phenethyl ester
-flavopiridol
-oleandrin
-ursolic acid
-butein
-betulinic acid

Scientific Papers found: Click to Expand⟱

2795-

CHr,

Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53

in-vitro,

Liver,

HepG2

ChemoSen↑, combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells
P53↑, chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells
ERK↑,
BAX↑, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2.
DR5↑,
Bcl-2↓,
Casp8↑, chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells
Cyt‑c↑,
Casp9↑,

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↑, demonstrated a significant AMPK activation after chrysin treatment in A549 cells
Akt↓, inhibited Akt/mammalian target of rapamycin (mTOR) activation
ChemoSen↑, Chrysin increases doxorubicin-induced AMPK activation to promote A549 cell death and growth inhibition
ROS↑, Recently, studies have confirmed that chrysin is a potent inducer of ROS and in A549 and other cancer cells

2803-

CHr,

5-FU,

Potentiating activities of chrysin in the therapeutic efficacy of 5-fluorouracil in gastric cancer cells

in-vitro,

GC,

AGS

chrysin doses of 40, 50, 60 and 80 µM, and 5-FU doses of 20, 25, 30 and 40 µM,

ChemoSen↑, combination of chrysin and 5-FU significantly increased cytotoxicity more than chrysin or 5-FU alone
TumCCA↑, 5-FU induced apoptosis through p53-p21 activity, while chrysin arrested the cell cycle in the G2/M phase
eff↑, chrysin was co-administered with cisplatin in HepG2 liver cancer cells (19), with docetaxel in A549 non-small cell lung cancer cells (18), and with metformin in breast cancer cells (20), showing synergistic effects
MDR1↓, chrysin inhibits the expression of MDR1

2788-

CHr,

Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action

Review,

Var,

*neuroP↑, Chrysin mitigates neurotoxicity, neuroinflammation, and oxidative stress.
*Inflam↓,
*ROS↓,
NF-kB↓, Chrysin treatment maintains the antioxidant armory and suppresses the activation of redox-active transcription factor NF-kB
*PCNA↓, Chrysin supplementation downregulated the expression of PCNA, COX-2, and NF-kB
*COX2↓,
ChemoSen↑, Chrysin is effective in attenuating cisplatin-induced expression of both COX-2 and iNOS
Hif1a↓, DU145: Chrysin suppressed the expression of HIF-1a of tumor cells in vitro and inhibited tumor cell-induced angiogenesis in vivo
angioG↓,
*chemoPv↑, Chrysin as an effective chemopreventive agent having the capability to obstruct DEN initiated and Fe-NTA promoted renal cancer in the rat model
PDGF↓, Chrysin functionally suppresses PDGF-induced proliferation and migration in VSMCs
*memory↑, Chrysin is effective in attenuating memory impairment, oxidative stress, acting as an antiaging agent
*RenoP↑, protected the kidney from damage
*PPARα↑, Chrysin significantly inhibits AGE-RAGE mediated oxidative stress and inflammation through PPAR-g activation
*lipidLev↓, Chrysin was able to decrease plasma lipids concentration because of its antioxidant properties
*hepatoP↑, Chrysin shows promising hepatoprotective and antihyperlipidemic effects, which are evidenced by the decreased levels of triglycerides, free fatty acids, total cholesterol, phospholipids, low-density lipoprotein-C, and very low-density lipoprotein
*cardioP⇅, Chrysin significantly ameliorated myocardial damage
*BioAv↓, despite its therapeutic potential, the bioavailability of chrysin and probably other flavonoids in humans is extremely low, mainly due to poor absorption, rapid metabolism, and rapid systemic elimination.

2591-

CHr,

doxoR,

Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway

in-vitro,

HCC,

Bel-7402

NRF2↓, chrysin is a potent Nrf2 inhibitor which sensitizes BEL-7402/ADM cells to ADM
ChemoSen↑, chrysin may be an effective adjuvant sensitizer to reduce anticancer drug resistance by down-regulating Nrf2 signaling pathway.
HO-1↓, Consequently, expression of Nrf2-downstream genes HO-1, AKR1B10, and MRP5 were reduced

2780-

CHr,

Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review

Review,

Var,

*antiOx↑, antioxidant (13), anti-inflammatory (14), antibacterial (15), anti-hypertensive (16), anti-allergic (17), vasodilator (18),
Inflam↓,
*hepatoP↑, anti-diabetic (19), anti-anxiety (10), anti-viral (20), anti-estrogen (21), liver protective (22), anti-aging (23), anti-seizure (24), and anti-cancer effects (25)
AntiCan↑,
Cyt‑c↑, (1) facilitating the release of cytochrome C from the mitochondria,
Casp3↑, (2) activating caspase-3 and inhibiting the activity of the XIAP molecule,
XIAP↓,
p‑Akt↓, (3) reducing AKT phosphorylation and triggering the PI3K pathway and induction of apoptosis
PI3K↑,
Apoptosis↑,
COX2↓, chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2.
FAK↓, ESCC cells: resultant blockage of the FAK/AKT signaling pathways
AMPK↑, A549: activation of AMPK by chrysin contributes to Akt suppression
STAT3↑, 4T1cell: inhibited STAT3 activation
MMP↓, Chrysin induces apoptosis through the intrinsic mitochondrial pathway that disrupts mitochondrial membrane potential (MMP) and increases DNA fragmentation.
DNAdam↑,
BAX↑, produces pro-apoptotic proteins, including Bax and Bak, and activates caspase-9 and caspase-3 in various cancer cells
Bak↑,
Casp9↑,
p38↑, chrysin can inhibit tumor growth by activating P38 MAPK and stopping the cell cycle
MAPK↑,
TumCCA↑,
ChemoSen↑, beneficial in inhibiting chemotherapy resistance of cancer cells
HDAC8↓, chrysin suppresses tumorigenesis by inhibiting histone deacetylase 8 (HDAC8)
Wnt↓, chrysin can attenuate Wnt and NF-κB signaling pathways
NF-kB↓,
angioG↓, chrysin can inhibit angiogenesis and inducing apoptosis in HTh7 cells, 4T1 mice, and MDA-MB-231 cells
BioAv↓, low bioavailability of flavonoids such as chrysin

2784-

CHr,

Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)

Review,

Var,

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,

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.

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

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

Core Metabolism/Glycolysis ⓘ

lipidLev↓, 1, NADPH↑, 1, PPARα↑, 1,

Cell Death ⓘ

MAPK↓, 1,

DNA Damage & Repair ⓘ

PCNA↓, 1,

Proliferation, Differentiation & Cell State ⓘ

PTEN↑, 1,

Angiogenesis & Vasculature ⓘ

VEGF↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 1, NF-kB↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, P450↓, 1,

Functional Outcomes ⓘ

cardioP⇅, 1, chemoPv↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 1, RenoP↑, 1, toxicity↓, 1, toxicity↝, 1,
Total Targets: 27

Scientific Paper Hit Count for: ChemoSen, chemo-sensitization

8 Chrysin
1 5-fluorouracil
1 doxorubicin

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#:1106  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Chrysin, , ChemoSen

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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