Rosmarinic acid / Casp3 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


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
3029- RosA,    Rosmarinic Acid, a Component of Rosemary Tea, Induced the Cell Cycle Arrest and Apoptosis through Modulation of HDAC2 Expression in Prostate Cancer Cell Lines
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
TumCP↓, tumCV↓, Apoptosis↑, HDAC2↓, PCNA↓, cycD1/CCND1↓, cycE/CCNE↓, P21↑, DNAdam↑, Casp3↑,
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↝,
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↑,
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↓,
3005- RosA,    Nanoformulated rosemary extract impact on oral cancer: in vitro study
- in-vitro, Laryn, HEp2
TumCCA↑, ROS↑, Bcl-2↓, BAX↑, Casp3↑, P53↑, necrosis↑, eff↑, BioAv↑,
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↓, TumCMig↓, ROS↓, Casp3↑, selectivity↑, Casp8↑, NLRP3↓,

Showing Research Papers: 1 to 6 of 6

* 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,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 3,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 2,   Bcl-2↓, 2,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp3↑, 5,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↓, 1,   Cyt‑c↑, 1,   MDM2↓, 1,   necrosis↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   HSP27↓, 1,   HSP70/HSPA5↑, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,   SESN2↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMTs↓, 1,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   ERK↓, 1,   FOXM1↓, 1,   HDAC2↓, 2,   mTOR↓, 1,   p‑mTOR↓, 1,   p‑P70S6K↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 2,  

Migration ⓘ

E-cadherin↑, 2,   ER-α36↓, 1,   GIT1↓, 1,   MARK4↓, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↑, 1,   COX2↓, 1,   ICAM-1↓, 1,   IL6↑, 1,   p‑IκB↓, 1,   NF-kB↓, 1,   p50↓, 1,   p65↓, 1,   p‑p65↓, 1,   PSA↓, 1,   TLR4↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 2,   Dose↝, 1,   eff↑, 3,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   FOXM1↓, 1,   HER2/EBBR2↓, 1,   IL6↑, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

ChemoSideEff↓, 1,   neuroP↑, 1,  
Total Targets: 95

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   HMGB1↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   PGE2↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

memory↑, 1,   neuroP↑, 1,  
Total Targets: 14

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
6 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#:42  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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