Resveratrol / HO-1 Cancer Research Results

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


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⟱
4703- PTS,  RES,    Pterostilbene and resveratrol: Exploring their protective mechanisms against skin photoaging - A scoping review
- NA, Nor, NA
*AntiAge↑, *eff↑, *Inflam↓, *AntiCan↑, *ROS↓, *Catalase↑, *GSR↑, *HO-1↑, *NAD↑, *NQO1↑, *SOD↑, *NRF2↑,
3062- RES,    Resveratrol enhances post-injury muscle regeneration by regulating antioxidant and mitochondrial biogenesis
- in-vivo, Nor, NA
*antiOx↑, *Keap1↓, *NRF2↑, *HO-1↑, *GPx↑, *SOD↑,
3061- RES,    The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
- Review, Var, NA
AhR↓, NRF2↑, *NQO1↑, *HO-1↑, *GSH↑, P53↑, Cyt‑c↑, Diablo↑, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, FOXO↑, p‑PI3K↓, p‑Akt↓, BIM↑, DR4↑, DR5↑, p27↑, cycD1/CCND1↓, SIRT1↑, NF-kB↓, ATF3↑,
3059- RES,    Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury
- in-vivo, Nor, HK-2
*RenoP↑, *Inflam↓, *NRF2↑, *HO-1↑, *SIRT1↑, *ROS↓, AntiAge↑,
3057- RES,    The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*NRF2↑, *Keap1↓, *ROS↓, *Apoptosis↓, *Inflam↓, *antiOx↑, *hepatoP↑, *neuroP↑, *cardioP↑, *RenoP↑, *AntiCan↑, *memory↑, *SOD↑, *GPx↑, *Catalase↑, *MDA↓, *NRF2↑, *HO-1↑, *ROS↓, *Aβ↓, *iNOS↓, *COX2↓, *GSH↑, *HO-1⇅, *SIRT1↑,
4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, *Inflam↓, *antiOx↑, *GSH↑, *HO-1↑, *iNOS↓, *BDNF↑, *p‑CREB↑, *PKA↑, *Bcl-2↑, *BAX↓, *IL1β↓, *IL6↓, *MMP9↓, *memory↑, *AMPK↑, *PGC-1α↓, *NF-kB↓, *Aβ↓, *SIRT1↑, *p‑tau↓, *PP2A↑, *lipid-P↓, *NLRP3↓, *BACE↓,
3612- RES,    Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential
- Review, AD, NA
*other↑, *Aβ↓, *Inflam↓, *NF-kB↓, *neuroP↑, *HO-1↑, *lipid-P↓, *COX2↓, *AMPK↑, *Catalase↑, *SOD↑, *GSR↑, *ROS↓, *MMP9↓, *cognitive↑, *SIRT1↑, *IL1β↓, *IL6↓,
3100- RES,    Neuroprotective effects of resveratrol in Alzheimer disease pathology
- Review, AD, NA
*neuroP↑, *BioAv↓, *Half-Life↓, *BioAv↑, *BBB↑, *NRF2↑, *BioAv↓, *BioAv↑, *SIRT1↑, *cognitive↑, *lipid-P↓, *HO-1↑, *SOD↑, *GSH↑, *GPx↑, *G6PD↑, *PPARγ↑, *AMPK↑, *Aβ↓,
3099- RES,    Resveratrol and cognitive decline: a clinician perspective
- Review, Nor, NA - NA, AD, NA
*antiOx↑, *ROS↓, *cognitive↑, *neuroP↑, *SIRT1↑, *AMPK↑, *GPx↑, *HO-1↑, *GSK‐3β↑, *COX2↓, *PGE2↓, *NF-kB↓, *NO↓, *Casp3↓, *MMP3↓, *MMP9↓, *MMP↑, *GSH↑, *other↑, *BioAv↑, *memory↑, *GlutMet↑, *BioAv↓, *Half-Life↓, *toxicity∅,
3092- RES,    Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action
- Review, BC, MDA-MB-231 - Review, BC, MCF-7
TumCP↓, tumCV↓, TumCI↓, TumMeta↓, *antiOx↑, *cardioP↑, *Inflam↓, *neuroP↑, *Keap1↓, *NRF2↑, *ROS↓, p62↓, IL1β↓, CRP↓, VEGF↓, Bcl-2↓, MMP2↓, MMP9↓, FOXO4↓, POLD1↓, CK2↓, MMP↓, ROS↑, Apoptosis↑, TumCCA↑, Beclin-1↓, Ki-67↓, ATP↓, GlutMet↓, PFK↓, TGF-β↓, SMAD2↓, SMAD3↓, Vim?, Snail↓, Slug↓, E-cadherin↑, EMT↓, Zeb1↓, Fibronectin↓, IGF-1↓, PI3K↓, Akt↓, HO-1↑, eff↑, PD-1↓, CD8+↑, Th1 response↑, CSCs↓, RadioS↑, SIRT1↑, Hif1a↓, mTOR↓,
2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, *BioAv↝, *Dose↝, *hepatoP↑, *neuroP↑, *AntiAg↑, *COX2↓, *antiOx↑, *ROS↓, *ROS↑, PI3K↓, Akt↓, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, NRF2↑, GPx↑, HO-1↑, BioEnh?, PTEN↑, ChemoSen↑, eff↑, mt-ROS↑, Warburg↓, Glycolysis↓, GlucoseCon↓, GLUT1↓, lactateProd↓, HK2↓, EGFR↓, cMyc↓, ROS↝, MMPs↓, MMP7↓, survivin↓, TumCP↓, TumCMig↓, TumCI↓,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ATF3↑, 1,   GPx↑, 1,   HO-1↑, 2,   NRF2↑, 2,   ROS↑, 1,   ROS↝, 1,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 1,   GlutMet↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   PFK↓, 1,   POLD1↓, 1,   SIRT1↑, 2,   Warburg↓, 1,  

Cell Death ⓘ

AhR↓, 1,   Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 1,   Bcl-2↓, 2,   Bcl-xL↓, 1,   BIM↑, 1,   CK2↓, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 1,   p27↑, 1,   survivin↓, 2,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   FOXO↑, 1,   FOXO4↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   PI3K↓, 2,   p‑PI3K↓, 1,   PTEN↑, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Slug↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Vim?, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

CRP↓, 1,   IL1β↓, 1,   NF-kB↓, 2,   PD-1↓, 1,   Th1 response↑, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh?, 1,   ChemoSen↑, 1,   eff↑, 4,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 87

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 3,   GPx↑, 4,   GSH↑, 5,   GSR↑, 2,   H2O2↓, 1,   HO-1↑, 10,   HO-1⇅, 1,   Keap1↓, 3,   lipid-P↓, 3,   mt-lipid-P↓, 1,   MDA↓, 2,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 3,   NRF2↑, 8,   ROS↓, 9,   ROS↑, 1,   SOD↑, 5,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 2,   PGC-1α↓, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 5,   p‑CREB↑, 1,   G6PD↑, 1,   GlutMet↑, 1,   NAD↑, 1,   NADH:NAD↑, 1,   PPARγ↑, 2,   SIRT1↑, 7,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   Cyt‑c∅, 1,   iNOS↓, 2,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

FOXO↑, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,  

Migration ⓘ

AntiAg↑, 2,   MMP3↓, 1,   MMP9↓, 4,   PKA↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 7,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 4,   BACE↓, 1,   NLRP3↓, 1,   PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BP↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiCan↑, 2,   cardioP↑, 2,   cognitive↑, 3,   hepatoP↑, 2,   memory↑, 3,   motorD↑, 1,   neuroP↑, 8,   RenoP↑, 2,   toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 84

Scientific Paper Hit Count for: HO-1, HMOX1
12 Resveratrol
1 Pterostilbene
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#:141  Target#:597  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

Home Page