Fisetin / HO-1 Cancer Research Results

FIS, Fisetin: Click to Expand ⟱
Features:
Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes.

-Note half-life 3-4hrs
- Oral BioAv low (40-50%)
Pathways:
- induce ROS production in cancer cells, but also known to reduce it.
Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells
Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Does not appear to lower antioxidants in cancer cells
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CD133↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Fisetin effect on Cancer Cells
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR signaling ↔ adaptive suppression Driver Loss of survival and growth signaling Fisetin consistently suppresses pro-survival PI3K/AKT signaling, supporting growth inhibition and sensitization to stress
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of inflammatory survival transcription NF-κB inhibition contributes to anti-inflammatory effects and reduced tumor-supportive signaling
3 Reactive oxygen species (ROS) ↑ ROS (context- & dose-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Fisetin can act as a pro-oxidant in cancer cells at higher stress/dose while remaining antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of intrinsic apoptosis Mitochondrial apoptosis occurs downstream of signaling and redox disruption
5 Cell cycle regulation ↑ G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream pathway inhibition rather than direct CDK blockade
6 Senescence / senolytic action ↑ senescence clearance (senescent-like tumor/stroma subsets) ↓ senescent cell burden (selective) Secondary Selective vulnerability of senescent-like cells Fisetin is commonly described as senolytic; in cancer context this may impact tumor microenvironment and therapy-induced senescence
7 MAPK stress signaling (JNK / p38) ↑ JNK / ↑ p38 (context-dependent) ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation often follows ROS increase and supports apoptotic signaling
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 activation reflects redox buffering responses rather than primary cytotoxicity
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT and protease activity limit invasive behavior downstream of signaling changes


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, p38↓, *antiOx↑, *neuroP↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, DNAdam↑, MMP↓, eff↑, ROS↑, cl‑PARP↑, Cyt‑c↑, Diablo↑, P53↑, p65↓, Myc↓, HSP70/HSPA5↓, HSP27↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, TumCCA↑, CDK2↓, CDK4↓, cycD1/CCND1↓, cycA1/CCNA1↓, P21↑, MMP2↓, MMP9↓, TumMeta↓, MMP1↓, MMP3↓, MMP7↓, MET↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↑, uPA↓, ChemoSen↑, EMT↓, Twist↓, Zeb1↓, cFos↓, cJun↓, EGF↓, angioG↓, VEGF↓, eNOS↓, *NRF2↑, HO-1↑, NRF2↓, GSTs↓, ATF4↓,
2858- FIS,    Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines
- in-vitro, BC, 4T1
HO-1↑, NRF2↑, MMP2↓, MMP9↓,
2861- FIS,    The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress
- Review, Nor, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, *ROS↓, *neuroP↑, *NO↑, BioAv↝, *BBB↑, *toxicity↑, *eff↑, *GSH↑, *SOD↑, *Aβ↓, *12LOX↓, *COX2↓, *Catalase↑, *Inflam↓, *TNF-α↓, *IL6↑, *lipid-P↓, NF-kB↓, IL1β↓, NRF2↑, HO-1↑, GSTs↑, cognitive↑, *BDNF↑,
2825- FIS,    Exploring the molecular targets of dietary flavonoid fisetin in cancer
- Review, Var, NA
*Inflam↓, *antiOx↓, *ERK↑, *p‑cMyc↑, *NRF2↑, *GSH↑, *HO-1↑, mTOR↓, PI3K↓, Akt↓, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, P21↑, p27↑, JNK↑, MMP2↓, MMP9↓, uPA↓, NF-kB↓, cFos↓, cJun↓, E-cadherin↑, Vim↓, N-cadherin↓, EMT↓, MMP↓, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, P53↑, COX2↓, PGE2↓, HSP70/HSPA5↓, HSP27↓, DNAdam↑, Casp3↑, Casp9↑, ROS↑, AMPK↑, NO↑, Ca+2↑, mTORC1↓, p70S6↓, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, eff↑, eff↑, eff↑, RadioS↑, ChemoSen↑, Half-Life↝,
2829- FIS,    Fisetin: An anticancer perspective
- Review, Var, NA
TumCP↓, TumCI↓, TumCCA↑, TumCG↓, Apoptosis↑, cl‑PARP↑, PKCδ↓, ROS↓, ERK↓, NF-kB↓, survivin↓, ROS↑, PI3K↓, Akt↓, mTOR↓, MAPK↓, p38↓, HER2/EBBR2↓, EMT↓, PTEN↑, HO-1↑, NRF2↑, MMP2↓, MMP9↓, MMP↓, Casp8↑, Casp9↑, TRAILR↑, Cyt‑c↑, XIAP↓, P53↑, CDK2↓, CDK4↓, CDC25↓, CDC2↓, VEGF↓, DNAdam↑, TET1↓, CHOP↑, CD44↓, CD133↓, uPA↓, CSCs↓,
2830- FIS,    Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent
- Review, Var, NA
TumCG↓, angioG↓, *ROS↓, TumCMig↓, VEGF↓, MAPK↑, NF-kB↓, PI3K↓, Akt↓, mTOR↓, NRF2↑, HO-1↑, ROS↓, Inflam↓, ER Stress↑, ROS↑, TumCP↓, ChemoSen↑, PTEN↑, P53↑, Casp3↑, Casp8↑, Casp9↑, COX2↓, Wnt↓, EGFR↓, Mcl-1↓, survivin↓, IAP1↓, IAP2↓, PGE2↓, β-catenin/ZEB1↓, DR5↑, MMP2↓, MMP9↓, FAK↓, uPA↓, EMT↓, ERK↓, JNK↑, p38↑, PKCδ↓, BioAv↓, BioAv↑, BioAv↑,

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 ⓘ

GSTs↓, 1,   GSTs↑, 1,   HO-1↑, 5,   NRF2↓, 1,   NRF2↑, 4,   ROS↓, 3,   ROS↑, 4,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   EGF↓, 1,   MMP↓, 3,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 2,  

Cell Death ⓘ

Akt↓, 4,   Apoptosis↑, 1,   BAD↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 3,   Casp8↑, 2,   Casp9↑, 3,   Cyt‑c↑, 3,   Diablo↑, 2,   DR5↑, 1,   IAP1↓, 1,   IAP2↓, 1,   JNK↑, 2,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↓, 2,   Myc↓, 1,   p27↑, 1,   p38↓, 2,   p38↑, 1,   survivin↓, 2,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP27↓, 2,   HSP70/HSPA5↓, 2,   IRE1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   P53↑, 4,   cl‑PARP↑, 3,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   cFos↓, 2,   CSCs↓, 1,   EMT↓, 4,   ERK↓, 2,   mTOR↓, 4,   mTORC1↓, 1,   PI3K↓, 4,   PTEN↑, 2,   TumCG↓, 2,   Wnt↓, 2,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 2,   FAK↓, 1,   Fibronectin↓, 1,   MET↓, 1,   MMP1↓, 1,   MMP2↓, 5,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 5,   N-cadherin↓, 2,   PKCδ↓, 2,   Snail↓, 1,   TET1↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 4,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↓, 1,   ATF4↑, 1,   EGFR↓, 2,   eNOS↓, 1,   NO↑, 1,   VEGF↓, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IL1β↓, 1,   Inflam↓, 1,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 2,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 3,   eff↑, 4,   Half-Life↝, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   HER2/EBBR2↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,  
Total Targets: 118

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 2,   Catalase↑, 1,   GSH↑, 2,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,   p‑cMyc↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL6↑, 1,   Inflam↓, 2,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↑, 1,  

Functional Outcomes ⓘ

neuroP↑, 2,   toxicity↑, 1,  
Total Targets: 24

Scientific Paper Hit Count for: HO-1, HMOX1
6 Fisetin
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#:78  Target#:597  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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