Rosmarinic acid / COX2 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↓">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


COX2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Cyclooxygenase-2 (COX-2) is an enzyme that plays a critical role in the conversion of arachidonic acid to prostaglandins, which are lipid compounds involved in various physiological processes, including inflammation, pain, and fever. COX-2 is an inducible enzyme, meaning its expression is typically low in normal tissues but can be upregulated in response to inflammatory stimuli, growth factors, and certain oncogenic signals.
-Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis.
-COX-2 is an inducible enzyme that is upregulated in response to pro-inflammatory signals, including cytokines (e.g., IL-1β, TNF-α) and growth factors.

COX-2 is often overexpressed in various tumors, including colorectal, breast, lung, and prostate cancers.
The prostaglandins produced by COX-2, particularly prostaglandin E2 (PGE2), have several effects that can facilitate cancer progression:
Cell Proliferation: PGE2 can promote the proliferation of cancer cells by activating signaling pathways such as the PI3K/Akt and MAPK pathways.
Nonselective NSAIDs, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. Epidemiological studies have suggested that regular use of NSAIDs may reduce the risk of certain cancers, particularly colorectal cancer.
Drugs specifically targeting COX-2, such as celecoxib, have been developed.

COX-2 and xanthine oxidase are ROS-producing pro-oxidant enzymes that contribute to inflammation. Elevated COX‑2 levels, often found in inflammatory conditions or certain types of cancers, can contribute to increased production of ROS.
Scientific Papers found: Click to Expand⟱
1048- RosA,  Ger,    Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis
- in-vivo, Colon, MC38
TumCMig↓, TumCI↓, PD-1↓, COX2↓, PD-L1↓,
3616- RosA,    Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders
- Review, AD, NA
*Inflam↓, *memory↑, *toxicity↓, *ROS↓, *Catalase↑, *SOD↑, *NRF2↑, *Aβ↓, *AChE↓, *Ca+2↓, *NO↓, *IL2↓, *COX2↓, *PGE2↓, *MMPs↓, *TNF-α↓, *iNOS↓, *TLR4↓, *cognitive↑, *cortisol↓, *lipid-P↓,
1745- RosA,    Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications
- Review, Var, NA - Review, AD, NA
ChemoSideEff↓, ChemoSen↑, antiOx↑, MMP2↓, MMP9↓, p‑AMPK↑, DNMTs↓, tumCV↓, COX2↓, E-cadherin↑, Vim↓, N-cadherin↓, EMT↓, Casp3↑, Casp9↓, ROS↓, GSH↑, ERK↓, Akt↓, ROS↓, NF-kB↓, p‑IκB↓, p50↓, p65↓, neuroP↑, Dose↝,
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↓,
3003- RosA,    Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases
- Review, Var, NA - Review, AD, NA - Review, Park, NA
*Inflam↓, *antiOx↑, *neuroP↑, *IL6↓, *IL1β↓, *NF-kB↓, *PGE2↓, *COX2↓, *MMP↑, *memory↑, *ROS↓, *Aβ↓, *HMGB1↓, TumCG↓, MARK4↓, Zeb1↓, MDM2↓, BNIP3↑, ASC↑, NLRP3↓, PI3K↓, Akt↓, Casp1↓, E-cadherin↑, STAT3↓, TLR4↓, MMP↓, ICAM-1↓, AMPK↓, IL6↑, MMP2↓, Warburg↓, Bcl-xL↓, Bcl-2↓, TumCCA↑, EMT↓, TumMeta↓, mTOR↓, HSP27↓, Casp3↑, GlucoseCon↓, lactateProd↓, VEGF↓, p‑p65↓, GIT1↓, FOXM1↓, cycD1/CCND1↓, CDK4↓, MMP9↓, HDAC2↓,
3007- RosA,    Hepatoprotective effects of rosmarinic acid: Insight into its mechanisms of action
- Review, NA, NA
*ROS↓, *lipid-P↓, *Inflam↓, *neuroP↑, *angioG↓, *eff↑, *AST↓, *ALAT↓, *GSSG↓, *eNOS↓, *iNOS↓, *NO↓, *NF-kB↓, *MMP2↓, *MDA↓, *TNF-α↓, *GSH↑, *SOD↑, *IL6↓, *PGE2↓, *COX2↓, *mTOR↑,
3017- RosA,  Per,    Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells
- in-vitro, Lung, A549
TumCD∅, ROS↓, IL1β↓, IL6↓, IL8↓, TNF-α↓, COX2↓, SOD2↓, FOXO1↓, NF-kB↓, JNK↓, antiOx↑, tumCV∅,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 2,   NRF2↑, 1,   ROS↓, 4,   SOD2↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↓, 1,   p‑AMPK↑, 1,   GlucoseCon↓, 2,   lactateProd↓, 2,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp3↑, 2,   Casp9↓, 1,   JNK↓, 1,   MDM2↓, 1,   TumCD∅, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,   tumCV∅, 1,  

Protein Folding & ER Stress ⓘ

HSP27↓, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,  

DNA Damage & Repair ⓘ

DNMTs↓, 1,   cl‑PARP↓, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   ERK↓, 1,   FOXM1↓, 1,   FOXO1↓, 1,   HDAC2↓, 2,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

E-cadherin↑, 2,   GIT1↓, 1,   MARK4↓, 1,   MMP2↓, 2,   MMP9↓, 2,   MMPs↓, 1,   N-cadherin↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 2,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↑, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↑, 1,   COX2↓, 4,   ICAM-1↓, 1,   IL1β↓, 1,   IL6↓, 2,   IL6↑, 1,   IL8↓, 1,   Inflam↓, 1,   p‑IκB↓, 1,   NF-kB↓, 2,   p50↓, 1,   p65↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   PD-L1↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 2,   Dose↝, 2,  

Clinical Biomarkers ⓘ

FOXM1↓, 1,   IL6↓, 2,   IL6↑, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

ChemoSideEff↓, 1,   neuroP↑, 1,  
Total Targets: 83

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   GSH↑, 2,   GSSG↓, 1,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 3,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 5,   SOD↑, 3,   VitC↑, 1,   VitE↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,  

Cell Death ⓘ

iNOS↓, 2,   p‑JNK↓, 1,   p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↑, 1,  

Migration ⓘ

Ca+2↓, 1,   MMP2↓, 1,   MMPs↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   eNOS↓, 1,   NO↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   HMGB1↓, 1,   IL1β↓, 2,   IL2↓, 1,   IL6↓, 3,   Inflam↓, 3,   NF-kB↓, 2,   PGE2↓, 3,   TLR4↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Hormonal & Nuclear Receptors ⓘ

cortisol↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,   P450↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BG↓, 1,   GutMicro↑, 1,   IL6↓, 3,  

Functional Outcomes ⓘ

AntiAge↑, 2,   cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 2,   motorD↓, 1,   neuroP↑, 3,   toxicity↓, 1,  
Total Targets: 54

Scientific Paper Hit Count for: COX2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein
7 Rosmarinic acid
1 Germacranolide
1 Perilla
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#:66  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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