Rosmarinic acid / GPx 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


GPx, Glutathione peroxidases: Click to Expand ⟱
Source:
Type:
Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS).
Glutathione peroxidase (GPx) refers to a family of antioxidant enzymes that play a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. There are several isoforms of GPx, including GPx1, GPx2, GPx3, and GPx4, each with distinct tissue distributions and functions.
GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers.

GPx expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.


Scientific Papers found: Click to Expand⟱
3026- RosA,    Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts
- in-vitro, Nor, NA
*ROS↓, *ATP↑, *NADPH↓, *HK2↓, *PFK2↓, *LDHA↓, *GSR↑, *GPx↑, *Prx↑, *Trx↑, *antiOx↑, *GSH↑, *ROS↓, *GlucoseCon↓, *lactateProd↓, *Glycolysis↝, *ATP↑, *NADPH↓, *PPP↓,
1748- RosA,    The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity
- Review, Var, NA
AntiCan↑, *BioAv↝, *CardioT↓, *Iron↓, *ROS↓, *SOD↑, *Catalase↑, *GPx↑, *NRF2↑, MARK4↓, MMP9↓, TumCCA↑, Bcl-2↓, BAX↑, Apoptosis↑, E-cadherin↑, N-cadherin↓, Vim↓, Gli1↓, HDAC2↓, Warburg↓, Hif1a↓, miR-155↓, p‑PI3K↑, ROS↑, *IronCh↑,
1749- RosA,    Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer
- Review, Var, NA
antiOx↑, eff↑, *toxicity↝, *BioAv↑, *ROS↓, SOD↑, Catalase↑, GPx↑, lipid-P↓, P450↓, chemoP↑, hepatoP↑, ChemoSen↑,
3014- RosA,    Rosmarinic Acid Supplementation Acts as an Effective Antioxidant for Restoring the Antioxidation/Oxidation Balance in Wistar Rats with Cadmium-Induced Toxicity
- in-vivo, Nor, NA
*antiOx↑, *Thiols↑, *GSH↑, *TAC↑, *SOD↑, *GPx↑, *Catalase↑, *ALP↓, *ALAT↓, *AST↓, *creat↓, *BUN↓, *H2O2↓, *MDA↓, *ROS↓, cardioP↑, hepatoP↑, neuroP↑,

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,   Catalase↑, 1,   GPx↑, 1,   lipid-P↓, 1,   ROS↑, 1,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

Warburg↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

Gli1↓, 1,   HDAC2↓, 1,   p‑PI3K↑, 1,  

Migration ⓘ

E-cadherin↑, 1,   MARK4↓, 1,   miR-155↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,   P450↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 2,   neuroP↑, 1,  
Total Targets: 29

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   GPx↑, 3,   GSH↑, 2,   GSR↑, 1,   H2O2↓, 1,   Iron↓, 1,   MDA↓, 1,   NRF2↑, 1,   Prx↑, 1,   ROS↓, 5,   SOD↑, 2,   TAC↑, 1,   Thiols↑, 1,   Trx↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   BUN↓, 1,   GlucoseCon↓, 1,   Glycolysis↝, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   NADPH↓, 2,   PFK2↓, 1,   PPP↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   creat↓, 1,  

Functional Outcomes ⓘ

CardioT↓, 1,   toxicity↝, 1,  
Total Targets: 35

Scientific Paper Hit Count for: GPx, Glutathione peroxidases
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#:418  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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