condition found tbRes List
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


selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
Scientific Papers found: Click to Expand⟱
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↑, A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress.
selectivity↑,
AR↓, rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153
TumCG↓, Rosemary extract modulates cell growth and induces cell cycle arrest in prostate cancer cell lines.
TumCCA↑,
CHOP↑, We observed an increase in overall protein expression of CHOP
PERK↓, decrease in PERK expression in prostate epithelial cells was observed following treatment with rosemary extract.
GRP78/BiP↑, rosemary extract induced BiP expression is essential for apoptosis.
PSA↓, AR and PSA is decreased and that of CHOP is increased in rosemary extract treated tissue lysates compared to lysates from control group animals.

1744- RosA,    Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity
- Review, Var, NA
chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↓, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells

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↓,

3011- RosA,    Rosmarinic Acid Exhibits Anticancer Effects via MARK4 Inhibition
- in-vitro, GBM, SH-SY5Y - in-vitro, Lung, A549 - in-vitro, Nor, HEK293 - in-vitro, Nor, MCF10
MARK4↓, rosmarinic acid (RA) as a potential inhibitor of MARK4.
p‑tau↓, suggesting that RA treatment decreases phosphorylation of tau as compared to untreated cells
selectivity↑, RA did not affect the viability of HEK293 and MCF-10A cells
*toxicity∅, studied concentration range RA has no cytotoxic activity for non-cancer cells, on the other hand, they have significant cytotoxicity for cancer cells.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
antiOx↑,1,   Apoptosis↑,1,   AR↓,1,   Bax:Bcl2↑,1,   BioAv↑,1,   Casp3↑,1,   Casp8↑,1,   chemoR↓,1,   ChemoSen↑,1,   ChemoSideEff↓,1,   CHOP↑,1,   CSCs↓,1,   DNAdam↑,1,   eff↑,2,   ER Stress↑,1,   Fenton↑,1,   FOXO4↑,1,   GRP78/BiP↑,1,   Half-Life↝,1,   HH↓,1,   MARK4↓,1,   MDR1↓,1,   NLRP3↓,1,   P-gp↓,1,   PERK↓,1,   PSA↓,1,   RadioS↑,1,   ROS↓,2,   ROS↑,1,   selectivity↑,4,   p‑tau↓,1,   TumCCA↑,1,   TumCG↓,1,   TumCMig↓,1,   tumCV↓,1,  
Total Targets: 35

Results for Effect on Normal Cells:
CardioT↓,1,   eff↑,1,   ERK↓,1,   GSH↑,1,   H2O2↑,1,   HO-1↑,1,   JNK↓,1,   MDA↓,1,   ROS↓,1,   SOD↓,1,   toxicity∅,1,  
Total Targets: 11

Scientific Paper Hit Count for: selectivity, selectivity
4 Rosmarinic acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:142  Target#:1110  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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