Rosmarinic acid / HO-1 Cancer Research Results

RosA, Rosmarinic acid: Click to Expand ⟱
Features: polyphenol
Polyphenol of many herbs - rosemary, perilla, sage mint and basil. Rosmarinic acid (RA) is predominantly found in a variety of medicinal and culinary herbs, especially those belonging to the Lamiaceae family, including rosemary (Rosmarinus officinalis), basil (Ocimum basilicum), sage (Salvia officinalis), thyme (Thymus vulgaris), and mints (Mentha spp.). In addition to the Lamiaceae family, RA is also present in plants from other families, such as Boraginaceae and Apiaceae.
-Rosmarinic acid is one of the hydroxycinnamic acids, and was initially isolated and purified from the extract of rosemary, a member of mint family (Lamiaceae)
-Its chemical structure allows it to act as a free radical scavenger by donating hydrogen atoms to stabilize ROS and free radicals.
RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals, thus interrupting oxidative chain reactions. It can modulate the activity of enzymes involved in OS, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), underscoring its potential role in preventing oxidative damage at the cellular level.
-divided as rosemary extract, carnosic acid, rosmarinic acid?

Summary:
-Capacity to chelate transition metal ions, particularly ironChelator (Fe2+) and copper (Cu2+)
-RA plus Cu(II)-induced oxidative DNA damage, which causes ROS
-rosmarinic acid (RA) as a potential inhibitor of MARK4↓ (inhibiting to tumor growth, invasion, and metastasis) activity (IC50 = 6.204 µM)

-Note half-life 1.5–2 hours.
BioAv water-soluble, rapid absorbtion
Pathways:
- varying results of ROS up or down in cancer cells. Plus a report of lowering ROS and no effect on Tumor cell viability.
However always seems to lower ROS↓ in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- No indication of Lowering AntiOxidant defense in Cancer Cells:
- Raises AntiOxidant defense in Normal Cells:(and perhaps even in cancer 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↓, VEGF↓, ROCK1↓, RhoA↓, NF-κB↓, ERK↓, MARK4↓
- reactivate genes thereby inhibiting cancer cell growth(weak) : HDAC2↓, DNMTs↓weak, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓??, LDHA↓, PFKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells (few references) : CSC↓, Hh↓, GLi1↓,
- Others: PI3K↓, AKT↓, STAT↓, 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 (dominant antioxidant effect) ↓ ROS Driver Antioxidant / redox buffering Rosmarinic acid is a strong phenolic antioxidant; cancer effects are largely redox-modulatory rather than cytotoxic
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of inflammatory survival signaling NF-κB inhibition explains anti-inflammatory, anti-proliferative, and chemopreventive effects
3 MAPK signaling (ERK / JNK / p38) ↓ ERK; ↑ JNK/p38 (context-dependent) ↔ minimal Secondary Stress-modulated signaling MAPK modulation reflects redox-sensitive signaling rather than direct kinase inhibition
4 Cell cycle regulation ↑ G0/G1 arrest (mild) ↔ spared Phenotypic Cytostatic growth control Growth inhibition is modest and non-cytotoxic in most models
5 Apoptosis ↑ apoptosis (weak / context-dependent) ↓ apoptosis Phenotypic Threshold-dependent cell death Apoptosis is not a dominant mechanism and usually requires high doses or co-stress
6 NRF2 antioxidant response ↑ NRF2 (adaptive) ↑ NRF2 (protective) Adaptive Antioxidant gene induction NRF2 activation reflects reinforcement of antioxidant capacity


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⟱
3615- RosA,    Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome
- Review, AD, NA - Review, Park, NA
*NLRP3↓, *Inflam↓, *neuroP↑, *NRF2↑, *TNF-α↓, *NF-kB↓, *HO-1↑, *ROS↓,
1744- RosA,    Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity
- Review, Var, NA
chemoR↓, ChemoSideEff↓, RadioS↑, ROS↓, ChemoSen↑, BioAv↑, Half-Life↝, antiOx↑, ROS↑, Fenton↑, DNAdam↑, Apoptosis↑, CSCs↓, HH↓, Bax:Bcl2↑, MDR1↓, P-gp↓, eff↑, eff↑, FOXO4↑, *eff↑, *ROS↓, *JNK↓, *ERK↓, *GSH↑, *H2O2↑, *MDA↓, *SOD↑, *HO-1↑, *CardioT↓, selectivity↑,
3001- RosA,    Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
- Review, Var, NA
TumCP↓, Apoptosis↑, TumMeta↓, Inflam↓, *antiOx↑, *AntiAge↑, *ROS↓, BioAv↑, Dose↝, NRF2↑, P-gp↑, ATP↑, MMPs↓, cl‑PARP↓, Hif1a↓, GlucoseCon↓, lactateProd↓, Warburg↓, TNF-α↓, COX2↓, IL6↓, HDAC2↓, GSH↑, ROS↓, ChemoSen↑, *BG↓, *IL1β↓, *TNF-α↓, *IL6↓, *p‑JNK↓, *p38↓, *Catalase↑, *SOD↑, *GSTs↑, *VitC↑, *VitE↑, *GSH↑, *GutMicro↑, *cardioP↑, *ROS↓, *MMP↓, *lipid-P↓, *NRF2↑, *hepatoP↑, *neuroP↑, *P450↑, *HO-1↑, *AntiAge↑, *motorD↓,
3002- RosA,    Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols
- Review, Var, NA
TumCG↓, TumCP↓, TumCCA↑, ChemoSen↑, NRF2↑, PERK↑, SESN2↑, HO-1↑, cl‑Casp3↑, ROS↑, UPR↑, ER Stress↑, CHOP↑, HER2/EBBR2↓, ER-α36↓, PSA↓, BAX↑, AR↓, P-gp↓, Cyt‑c↑, HSP70/HSPA5↑, eff↑, p‑Akt↓, p‑mTOR↓, p‑P70S6K↓, cl‑PARP↑, eff↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Fenton↑, 1,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 2,   ROS↓, 2,   ROS↑, 2,  

Mitochondria & Bioenergetics

ATP↑, 1,  

Core Metabolism/Glycolysis

GlucoseCon↓, 1,   lactateProd↓, 1,   Warburg↓, 1,  

Cell Death

p‑Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 1,   Bax:Bcl2↑, 1,   cl‑Casp3↑, 1,   Cyt‑c↑, 1,  

Kinase & Signal Transduction

HER2/EBBR2↓, 1,  

Protein Folding & ER Stress

CHOP↑, 1,   ER Stress↑, 1,   HSP70/HSPA5↑, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes

SESN2↑, 1,  

DNA Damage & Repair

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

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

CSCs↓, 1,   FOXO4↑, 1,   HDAC2↓, 1,   HH↓, 1,   p‑mTOR↓, 1,   p‑P70S6K↓, 1,   TumCG↓, 1,  

Migration

ER-α36↓, 1,   MMPs↓, 1,   TumCP↓, 2,   TumMeta↓, 1,  

Angiogenesis & Vasculature

Hif1a↓, 1,  

Barriers & Transport

P-gp↓, 2,   P-gp↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   IL6↓, 1,   Inflam↓, 1,   PSA↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

BioAv↑, 2,   chemoR↓, 1,   ChemoSen↑, 3,   Dose↝, 1,   eff↑, 4,   Half-Life↝, 1,   MDR1↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers

AR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   PSA↓, 1,  

Functional Outcomes

ChemoSideEff↓, 1,  
Total Targets: 62

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 1,   GSH↑, 2,   GSTs↑, 1,   H2O2↑, 1,   HO-1↑, 3,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 4,   SOD↑, 2,   VitC↑, 1,   VitE↑, 1,  

Mitochondria & Bioenergetics

MMP↓, 1,  

Cell Death

JNK↓, 1,   p‑JNK↓, 1,   p38↓, 1,  

Proliferation, Differentiation & Cell State

ERK↓, 1,  

Immune & Inflammatory Signaling

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Protein Aggregation

NLRP3↓, 1,  

Drug Metabolism & Resistance

eff↑, 1,   P450↑, 1,  

Clinical Biomarkers

BG↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes

AntiAge↑, 2,   cardioP↑, 1,   CardioT↓, 1,   hepatoP↑, 1,   motorD↓, 1,   neuroP↑, 2,  
Total Targets: 35

Scientific Paper Hit Count for: HO-1, HMOX1
4 Rosmarinic acid
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#:142  Target#:597  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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