Rosmarinic acid / P450 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


P450, cytochrome P450 (CYP) family: Click to Expand ⟱
Source:
Type:
The cytochrome P450 (CYP) family includes many isoenzymes that play key roles in metabolizing endogenous substances (like hormones) and xenobiotics (including drugs and toxins). Changes in the expression of these enzymes in various cancers can affect carcinogen activation, drug metabolism, and overall tumor biology, influencing both cancer risk and prognosis.

CYP1B1
– Frequently overexpressed in several cancers including breast, ovarian, prostate, and colorectal cancers.
– Its expression is often low in normal tissues, making it a potential target for selective cancer therapies.

2. CYP3A4 and CYP3A5
These enzymes are highly expressed in the liver, but their expression is also observed in extrahepatic tissues.
– In cancer, CYP3A enzymes can be variably expressed; for instance, CYP3A4 may be upregulated in some liver cancers but downregulated in others.

3. CYP2E1
– CYP2E1 is expressed in the liver and extrahepatic tissues.
– Elevated CYP2E1 activity can lead to increased production of reactive oxygen species (ROS), contributing to DNA damage and cancer progression.

4. CYP19A1 (Aromatase)
– Aromatase converts androgens to estrogens and is expressed in adipose tissue as well as in certain tumors such as breast cancer.
– Its local expression in breast tumors can increase estrogen levels, promoting hormone-dependent tumor growth.

5. CYP2C Family (e.g., CYP2C8, CYP2C9, CYP2C19)
– These enzymes are involved in metabolizing various drugs and are expressed in the liver and intestines.
– Their expression levels can be altered in different tumor types, potentially affecting drug metabolism.

CYP450 enzymes are a large family with diverse roles in cancer biology.
• Their expression in cancers (e.g., CYP1B1, CYP3A4/5, CYP2E1, CYP19A1) has been linked to both the development and progression of tumors, as well as influencing responses to therapy.


Scientific Papers found: Click to Expand⟱
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↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics

ATP↑, 1,  

Core Metabolism/Glycolysis

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

Cell Death

Apoptosis↑, 1,  

DNA Damage & Repair

cl‑PARP↓, 1,  

Proliferation, Differentiation & Cell State

HDAC2↓, 1,  

Migration

MMPs↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature

Hif1a↓, 1,  

Barriers & Transport

P-gp↑, 1,  

Immune & Inflammatory Signaling

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

Drug Metabolism & Resistance

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

Clinical Biomarkers

IL6↓, 1,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

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

Mitochondria & Bioenergetics

MMP↓, 1,  

Cell Death

p‑JNK↓, 1,   p38↓, 1,  

Immune & Inflammatory Signaling

IL1β↓, 1,   IL6↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance

P450↑, 1,  

Clinical Biomarkers

BG↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes

AntiAge↑, 2,   cardioP↑, 1,   hepatoP↑, 1,   motorD↓, 1,   neuroP↑, 1,  
Total Targets: 26

Scientific Paper Hit Count for: P450, cytochrome P450 (CYP) family
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#:1061  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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