Carvone / GSH Cancer Research Results

CRV, Carvone: Click to Expand ⟱
Features:

Carvone — Carvone is a chiral oxygenated monocyclic monoterpene ketone found mainly as enantiomeric forms in spearmint, caraway, dill, and related essential oils. It is best classified as a small-molecule natural product / volatile terpenoid flavor-fragrance compound, commonly abbreviated CRV. The biologically relevant forms are often reported as l-carvone, d-carvone, R-carvone, or S-carvone, but naming conventions are inconsistent across papers, so note the exact enantiomer stated by each source.

Primary mechanisms (ranked):

  1. Induction of cancer-cell apoptosis through p53, Bad, caspase-3 activation, PARP cleavage, and DNA-damage-associated stress signaling.
  2. Suppression of migration, adhesion, invasion, and metastatic behavior, especially through FAK-related signaling in breast cancer models.
  3. Context-dependent oxidative stress modulation, including ROS increase and DNA damage at cytotoxic in-vitro concentrations.
  4. Inhibition of proliferative survival pathways, including JAK/STAT3 in gastric cancer and p38 MAPK-related signaling in myeloma models.
  5. Cell-cycle disruption, reported as S-phase, G0/G1, or G2/M arrest depending on enantiomer, cancer model, and concentration.
  6. Possible chemopreventive activity in animal skin-carcinogenesis models, but not established as a clinically validated anticancer agent.

Bioavailability / PK relevance: Carvone is lipophilic and volatile, with oral, dermal, and inhalational exposure relevance depending on formulation. Human PK/metabolism data exist for ingestion-correlated and topical/percutaneous exposure contexts, but anticancer studies generally use concentrations that are not directly matched to validated systemic anticancer exposure. Essential-oil delivery introduces variability from enantiomer ratio, co-terpenes, oxidation products, and formulation.

In-vitro vs systemic exposure relevance: Common anticancer in-vitro effects occur at high micromolar to millimolar or microgram-per-millilitre ranges, and breast-cancer IC50 values around the millimolar range have been reported. These levels are likely above ordinary dietary flavor exposure and may exceed practical systemic exposure from food-like intake. Interpretation should therefore be concentration-constrained and formulation-dependent.

Clinical evidence status: Preclinical for cancer. Evidence includes cancer cell-line studies, animal chemoprevention/tumor models, and mechanistic studies, but no credible cancer RCTs of carvone as a therapeutic agent were identified. Human studies involving carvone-containing preparations exist for non-cancer indications or mixtures, but they should not be treated as direct anticancer evidence for isolated carvone.

Safety / regulatory status: Carvone is listed as a FEMA GRAS flavoring substance with CFR flavor-use reference, but this applies to intended flavor-use exposure, not therapeutic dosing. Major constraints include skin sensitization potential, enantiomer/formulation variability, volatile exposure, and uncertain safety at high supplemental or pharmacologic doses. Fragrance safety assessment data indicate no genotoxic concern under reviewed conditions, but l-carvone is considered a skin sensitizer.

Carvone Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Apoptosis execution ↑ p53, ↑ Bad, ↑ cleaved caspase-3, ↑ cleaved PARP Lower sensitivity reported in some normal-cell comparisons G Pro-apoptotic cytotoxicity Most central anticancer mechanism; strongest evidence is in vitro and concentration-dependent.
2 Migration adhesion invasion ↓ migration, ↓ adhesion, ↓ invasion, ↓ FAK activation Not well-defined G Anti-metastatic phenotype Mechanistically important for breast cancer models; therapeutic leverage is plausible but not clinically validated.
3 ROS and DNA damage stress ↑ ROS, ↑ DNA damage markers, ↑ apoptotic stress Context-dependent antioxidant or cytoprotective effects reported outside cancer R/G Stress-mediated apoptosis ROS appears pro-apoptotic in several cancer contexts; antioxidant effects in non-cancer models make this axis context-dependent.
4 JAK STAT3 survival signaling ↓ JAK/STAT3 signaling in gastric cancer models Not well-defined G Reduced survival signaling Promising but model-specific; should not be generalized across all tumor types without direct evidence.
5 p38 MAPK signaling ↓ p38 MAPK-related signaling in myeloma models Not well-defined G Growth and invasion suppression Reported in myeloma; secondary/contextual relative to apoptosis and motility effects.
6 Cell cycle control ↑ arrest at S, G0/G1, or G2/M depending on model Not well-defined G Reduced proliferation Direction of arrest is inconsistent across cancer systems and enantiomer reports; keep model-specific.
7 Mitochondrial apoptosis ↓ mitochondrial membrane potential reported in some models, ↑ caspase-linked apoptosis Context-dependent R/G Intrinsic apoptosis support Relevant when mitochondrial depolarization or ROS-mediated apoptosis is directly measured.
8 Angiogenesis tumor microenvironment ↓ angiogenesis stimulus in Ehrlich tumor context Not well-defined G Reduced tumor support phenotype Evidence is less mature than direct cancer-cell apoptosis and migration data.
9 NRF2 redox adaptation ↔ or uncertain Possible cytoprotective relevance in oxidative stress models G Unresolved redox adaptation
10 Clinical Translation Constraint High in-vitro concentrations may not map to achievable systemic exposure Skin sensitization and exposure-route constraints G Limits translational confidence Bioavailability, enantiomer identity, essential-oil composition, and flavor-use versus therapeutic-dose safety are the main constraints.

P: 0–30 min R: 30 min–3 hr G: >3 hr
GSH, Glutathione: Click to Expand ⟱
Source:
Type:
Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.
Scientific Papers found: Click to Expand⟱
6520- CRV,    Health Benefits and Pharmacological Properties of Carvone
- Review, Nor, NA
*Bacteria↓, *AntiFungal↑, *antiOx↑, *Inflam↓, AntiCan↑, *AntiDiabetic↑, *Obesity↓, TumCCA↑, *AntiArt↑, Imm↑, *P450↓, *GSR↑, GSTs↑, GSH↑, BAX↑, Casp3↑, TumCP↓, TumCMig↓, Apoptosis↑,
6521- CRV,    L-carvone induces p53, caspase 3 mediated apoptosis and inhibits the migration of breast cancer cell lines
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, Nor, MCF10
TumCP↓, TumCMig↓, Apoptosis↑, TumCCA↑, DNAdam↑, ROS↑, GSH↑, P53↑, BAD↑, cl‑Casp3↑, cl‑PARP↑, Apoptosis↑,
6525- CRV,    D-carvone induced ROS mediated apoptotic cell death in human leukemic cell lines (Molt-4)
- in-vitro, AML, NA
tumCV↓, ROS↑, antiOx↓, MMP↓, Apoptosis↑, Casp8↑, Casp9↑, Casp3↑, *neuroP↑, AntiCan↑, *AntiArt↑, TBARS↑, SOD↓, GSH↓, Catalase↓,
6527- CRV,    Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events
- in-vivo, Melanoma, NA
AntiTum↑, P450↓, GSR↑, GSTs↑, GSH↑, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, p53 Wildtype↓, chemoPv↑, Apoptosis↑,
6529- CRV,    D-Carvone Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting Oxidative Stress and TGF-ß 1/SMAD3 Signaling Pathway
- in-vivo, Nor, NA
*ALAT↓, *AST↓, *MDA↓, *SOD↑, *GSH↑, *TAC↑, *eff↑, *TGF-β1↓, *SMAD3↓, *MMP9↑, *NRF2↑, *antiOx↑, *hepatoP↑, *Inflam↓, *NF-kB↓, *NO↓, *cAMP↑, *ROS↓,
6531- CRV,    D-carvone attenuates LPS-induced acute lung injury via TLR4/NF-κB and Nrf2/HO-1 signaling pathways in rats
- in-vivo, Nor, NA
*TRAF1↓, *IL1β↓, *TNF-α↓, *ROS↓, *MDA↓, *GSH↑, *SOD↑, *Inflam↓, *NRF2↑, *Bcl-2↑, *IL8↓, *antiOx↑,

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,   Catalase↓, 1,   GSH↓, 1,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 2,   ROS↑, 2,   SOD↓, 1,   TBARS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Apoptosis↑, 5,   BAD↑, 1,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 2,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   p53 Wildtype↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Migration ⓘ

TumCMig↓, 2,   TumCP↓, 2,  

Immune & Inflammatory Signaling ⓘ

Imm↑, 1,  

Drug Metabolism & Resistance ⓘ

P450↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,   chemoPv↑, 1,  
Total Targets: 31

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

AntiArt↑, 2,  

Redox & Oxidative Stress ⓘ

antiOx↑, 3,   GSH↑, 2,   GSR↑, 1,   MDA↓, 2,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 2,   TAC↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   cAMP↑, 1,  

Cell Death ⓘ

Bcl-2↑, 1,  

Migration ⓘ

MMP9↑, 1,   SMAD3↓, 1,   TGF-β1↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL8↓, 1,   Inflam↓, 3,   NF-kB↓, 1,   TNF-α↓, 1,   TRAF1↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,   P450↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

AntiDiabetic↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   Obesity↓, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 32

Scientific Paper Hit Count for: GSH, Glutathione
6 Carvone
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#:411  Target#:137  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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