Rosmarinic acid / PERK 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


PERK, protein kinase-like ER kinase: Click to Expand ⟱
Source:
Type:
PERK is a type of kinase that is activated in response to endoplasmic reticulum (ER) stress, which occurs when the ER is overwhelmed with unfolded or misfolded proteins. Once activated, PERK phosphorylates and activates the eukaryotic translation initiation factor 2 alpha (eIF2α), leading to the attenuation of global protein synthesis and the induction of specific genes involved in the UPR.
PERK is overexpressed in various types of cancer, including breast, lung, and colon cancer, and that its expression is often associated with poor prognosis.
PERK has been shown to have both tumor-suppressive and tumor-promoting roles, depending on the context.
-PERK, as the sensor of ER stress.
Scientific Papers found: Click to Expand⟱
3025- RosA,    Rosmarinic acid alleviates intestinal inflammatory damage and inhibits endoplasmic reticulum stress and smooth muscle contraction abnormalities in intestinal tissues by regulating gut microbiota
- in-vivo, IBD, NA
*GutMicro↑, *ROCK1↓, *Rho↓, *CaMKII ↓, *Zeb1↓, *ZO-1↓, *E-cadherin↓, *IL1β↓, *IL6↓, *TNF-α↓, *GRP78/BiP↓, *PERK↓, *IRE1↓, *ATF6↓, *CHOP↓, *Casp12↓, *Casp9↓, *BAX↓, *Casp3↓, *Cyt‑c↓, *RIP1↓, *MLKL↓, *IL10↑, *Bcl-2↑, *ER Stress↓,
3033- RosA,    Rosemary (Rosmarinus officinalis) Extract Modulates CHOP/GADD153 to Promote Androgen Receptor Degradation and Decreases Xenograft Tumor Growth
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, LNCaP - vitro+vivo, NA, NA
ER Stress↑, selectivity↑, AR↓, TumCG↓, TumCCA↑, CHOP↑, PERK↓, GRP78/BiP↑, PSA↓,
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↑,
3024- RosA,    rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice
- in-vivo, Sepsis, NA
*Ferroptosis↓, *GRP78/BiP↓, *PERK↓, *ATF4↓, *Sepsis↓, *GSH↑, *SOD↑, *Catalase↑,
3020- RosA,    Protective Effect of Rosmarinic Acid on Endotoxin-Induced Neuronal Damage Through Modulating GRP78/PERK/MANF Pathway
- in-vivo, Nor, NA - in-vitro, NA, SH-SY5Y
*cognitive↑, *PERK↓, *GRP78/BiP↓, *ER Stress↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   NRF2↑, 1,   ROS↑, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   BAX↑, 1,   cl‑Casp3↑, 1,   Cyt‑c↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP70/HSPA5↑, 1,   PERK↓, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

SESN2↑, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

p‑mTOR↓, 1,   p‑P70S6K↓, 1,   TumCG↓, 2,  

Migration ⓘ

ER-α36↓, 1,   TumCP↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 2,   HER2/EBBR2↓, 1,   PSA↓, 2,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   Ferroptosis↓, 1,   GSH↑, 1,   SOD↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Bcl-2↑, 1,   Casp12↓, 1,   Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   Ferroptosis↓, 1,   MLKL↓, 1,   RIP1↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Protein Folding & ER Stress ⓘ

ATF6↓, 1,   CHOP↓, 1,   ER Stress↓, 2,   GRP78/BiP↓, 3,   IRE1↓, 1,   PERK↓, 3,  

Migration ⓘ

E-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   Zeb1↓, 1,   ZO-1↓, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL10↑, 1,   IL1β↓, 1,   IL6↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 34

Scientific Paper Hit Count for: PERK, protein kinase-like ER kinase
5 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#:617  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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