Database Query Results : Rosmarinic acid, , TumCMig

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


TumCMig, Tumor cell migration: Click to Expand ⟱
Source:
Type:
Tumor cell migration is a critical process in cancer progression and metastasis, which is the spread of cancer cells from the primary tumor to distant sites in the body.
Scientific Papers found: Click to Expand⟱
3035- RosA,    Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling
- in-vitro, PC, NA - in-vivo, NA, NA
Gli1↓, RA dramatically down-regulated Gli1 and its downstream targets
TumCCA↑, RA induced G1/S cell cycle arrest and apoptosis in the PDAC cells through regulating the expression of P21, P27, CDK2, Cyclin E, Bax, and Bcl-2, it inhibited the PDAC cell migration and invasion via E-cadherin and MMP-9.
TumCMig↓,
TumCI↓,
CDK2↓,
cycE/CCNE↓,
P21↑,
p27↑,

3027- RosA,    Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway
- in-vitro, HCC, SMMC-7721 cell
TumCP↓, RosA significantly inhibited the proliferation of SMMC-7721 cells and induced G1 arrest and apoptosis in a dose-dependent manner
TumCCA↑,
Apoptosis↑,
EMT↓, RosA might inhibit cell invasion by regulating epithelial-mesenchymal transition
TumCI↓,
PI3K↓, IGF-1 could reverse the inhibition of PI3K/AKT/mTOR signal pathway by RosA
Akt↓,
mTOR↓,
TumCMig↓, inhibition effect of migration and invasion by regulation MMPs, Vimentin and EMT.
MMPs↓,
Vim↓,

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↓, RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1
COX2↓,
PD-L1↓,

1747- RosA,    Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review
- Review, BC, MDA-MB-231 - Review, BC, MDA-MB-468
TumCCA↑, Rosmarinic Acid arrests the G0/G1 phase in MDA-MB-231 cells and the S-phase in MDA-MB-468 cells following apoptosis (interruption of the G2/M process).
TNF-α↑, Rosmarinic Acid enhanced the expression of TNF (tumor necrosis factor), GADD45A (growth arrest and DNA damage-inducible 45 alpha), and the proapoptotic BNIP3
GADD45A↑,
BNIP3↑,
survivin↓, IRC5 (Survivin) inhibition appears to be the most important effect of Rosmarinic Acid on MDA-MB-468 cells
Bcl-2↓, Bcl-2 gene is downregulated while the Bax gene expression is increased in the presence of Rosmarinic Acid
BAX↑,
HH↓, The experiments showed that Rosmarinic Acid inhibited Hh signaling genes’ expression in BCSCs.
eff↑, rosemary extract with Rosmarinic Acid and carnosic acid as primary ingredients inhibited cancer cell viability in the ER+, HER2+, and TNBC subtypes (MDA-MB-231 and MDA-MB-468 cells)
ChemoSen↑, The inhibition of NF-κB increases chemotherapy and radiation results
RadioS↑,
TumCP↓, In vitro experiments in MDA-MB-231 cancer cells treated with Rosmarinic Acid have shown that proliferation and migration were significantly attenuated, and eventually, cells were led to apoptosis
TumCMig↓,
Apoptosis↑,
RenoP↑, Rosmarinic Acid decreased the hepatic and renal toxicity induced by methotrexate, as well as the cardiotoxicity of doxorubicin
CardioT↓,

3016- RosA,    Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling
- in-vitro, HNSCC, UM-SCC-6 - in-vitro, HNSCC, UM-SCC-10B
chemoP↓,
EGF↓, RA as an inhibitor of epidermal growth factor (EGF) st
tumCV↓, RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines.
TumCMig↓,
ROS↓,
PI3K↓, down-regulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ERK) pathways.
Akt↓,
ERK↓,
antiOx↑, RA serves as a potent antioxidant in HNSCC
p‑EGFR↓, RA’s ability to attenuate EGFR phosphorylation

3008- RosA,    Rosmarinic acid decreases viability, inhibits migration and modulates expression of apoptosis-related CASP8/CASP3/NLRP3 genes in human metastatic melanoma cells
- in-vitro, Melanoma, SK-MEL-28
tumCV↓, • RA decreases viability and inhibits migration of human metastatic melanoma cells.
TumCMig↓,
ROS↓, RA decreases extracellular and intracellular ROS, and improvements in NPSH and PSH levels.
Casp3↑, RA modulates expression of apoptosis-related genes and increases the enzymatic activity of caspase 3 protein.
selectivity↑, On the other hand, it has no cytotoxic effect on non-tumoral cells.
Casp8↑, RA strongly upregulates the gene expression of the caspase 8 and caspase 3, and downregulates NLRP3 inflammasome expression.
NLRP3↓,


* 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 ⓘ

antiOx↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

EGF↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp8↑, 1,   p27↑, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,  

DNA Damage & Repair ⓘ

GADD45A↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   Gli1↓, 1,   HH↓, 1,   mTOR↓, 1,   PI3K↓, 2,  

Migration ⓘ

MMPs↓, 1,   TumCI↓, 3,   TumCMig↓, 6,   TumCP↓, 2,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

p‑EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   PD-1↓, 1,   PD-L1↓, 1,   TNF-α↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

p‑EGFR↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

CardioT↓, 1,   chemoP↓, 1,   RenoP↑, 1,  
Total Targets: 44

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCMig, Tumor cell migration
6 Rosmarinic acid
1 Germacranolide
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#:326  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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