Linalool Cancer Research Results

LIN, Linalool: Click to Expand ⟱
Features:

Linalool — Linalool is a naturally occurring acyclic monoterpene tertiary alcohol and volatile, lipophilic phytochemical found in many essential oils, notably lavender, coriander, basil, rosewood, and related aromatic plants. It is formally classified as a small-molecule monoterpenoid and fragrance/flavor compound; common abbreviations are LIN and Lin. Linalool occurs as (R)- and (S)-enantiomers with differing sensory and potentially pharmacological properties. In oncology it should be classified as a preclinical experimental bioactive rather than an established anticancer treatment.

Primary mechanisms (ranked):

  1. Induction of apoptosis, prominently involving mitochondrial membrane depolarization, Bcl-2-family regulation, cytochrome-c/caspase signaling, and in some models p53/CDKI activation.
  2. Cell-cycle arrest through modulation of cyclins, CDKs, p21, p27, p18 and related checkpoint machinery, with the arrest phase varying by cancer model.
  3. Suppression or remodeling of proliferative survival signaling, particularly PI3K/Akt/mTOR and Ras/MAPK pathways; Akt/ERK responses can become adaptive or pro-survival at high concentrations.
  4. ROS-mediated oxidative cytotoxicity, including hydroxyl-radical generation, lipid peroxidation and mitochondrial injury in selected cancer models; this is dose- and model-dependent rather than a universal linalool mechanism.
  5. Chemosensitization, particularly enhancement of doxorubicin accumulation and cytotoxicity in experimental models, including drug-resistant breast cancer cells.
  6. Suppression of migration, invasion and proliferative phenotype in selected tumor models.
  7. NR3C2 stabilization with NFKBIZ induction and downstream NF-κB suppression in gastric cancer, representing a newer cancer-specific mechanistic axis requiring replication.
  8. PGK1 suppression and PPARγ-associated signaling in breast cancer, currently supported primarily by mechanistic preclinical evidence.
  9. Context-dependent NRF2/redox modulation in normal tissues and tumor-bearing animals; NRF2 activation is better established as a tissue-protective response than as a core direct anticancer mechanism.

Bioavailability / PK relevance: Linalool is rapidly systemically absorbed after oral administration but undergoes substantial distribution and metabolism. In healthy humans receiving 100 mg orally, mean serum Cmax was approximately 85.5 ng/mL at about 1.15 h, with an apparent half-life of approximately 3.9 h and AUC of approximately 442 h·ng/mL. Its volatility, poor aqueous solubility, rapid metabolism and formulation dependence constrain systemic anticancer exposure. Lipid, cyclodextrin, nanoemulsion and nanoparticle formulations are being investigated to improve delivery.

In-vitro vs systemic exposure relevance: There is a major exposure gap. A human 100-mg oral dose produced a Cmax of approximately 85.5 ng/mL, equivalent to roughly 0.55 µM linalool, whereas many anticancer experiments use tens to hundreds of micromolar concentrations and some mechanistic studies use 1–2.5 mM. Thus, many commonly reported direct anticancer concentrations exceed measured human systemic exposure by approximately two to three or more orders of magnitude. Low-micromolar effects reported in a few cell models are more pharmacokinetically interesting but remain unvalidated clinically. Formulation or local-delivery strategies would likely be required to reproduce many experimental exposures.

Clinical evidence status: Preclinical. Evidence includes cancer-cell experiments and several rodent/xenograft studies, including prostate, colon, breast, gastric and ovarian cancer models. Human pharmacokinetic data are available, but there is no established human anticancer efficacy evidence and no approved oncology indication for linalool. Human use of linalool-containing essential oils is principally in fragrance, flavor and supportive/aromatherapy contexts rather than tumor treatment.

Linalool Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial apoptosis ↓ MMP; ↑ cytochrome c; ↑ caspase-3; ↑ PARP cleavage; ↑ apoptosis Less pronounced in some comparative models (model-dependent) R/G Programmed cancer-cell death One of the most consistently reproduced anticancer effects across leukemia, liver, oral, prostate, breast and other cancer models.
2 Cell-cycle checkpoint control ↑ p21; ↑ p27; ↑ p18; ↓ CDK4; ↓ cyclin A; ↑ G0/G1 or G2/M arrest (model-dependent) Less well characterized G Proliferation arrest Phase of arrest differs among tumor types, so linalool should not be assigned one universal cell-cycle phase.
3 PI3K Akt mTOR survival signaling ↓ PI3K/Akt signaling at lower experimental concentrations; ↓ mTOR at higher concentrations; ↑ Akt can occur as adaptive signaling (dose-dependent) Context-dependent R/G Reduced survival signaling Strong mechanistic evidence in selected models, but signaling is biphasic. High-dose Akt activation should not be incorrectly recorded as uniform Akt inhibition.
4 Oxidative stress and lipid peroxidation ↑ ROS; ↑ hydroxyl radicals; ↑ lipid peroxidation; ↑ apoptosis (dose-dependent) ↔ or ↓ oxidative stress in some normal tissues (model-dependent) R/G Selective oxidative cytotoxicity Colon models demonstrate cancer-selective hydroxyl-radical generation. HepG2 ROS generation was prominent at approximately 2 mM, making exposure highly relevant.
5 Mitochondrial ROS MAPK stress response ↑ ROS; ↓ MMP; ↑ JNK; ↑ ERK at high concentration (dose-dependent) Not established R/G Stress-mediated apoptosis ROS scavenging partially prevents mitochondrial depolarization and ERK/JNK activation in HepG2 cells, supporting a causal ROS component.
6 p53 and CDKI signaling ↑ p53; ↑ p21; ↑ p27; ↑ GADD45α; ↑ JNK Relative sparing reported in normal hematopoietic cells in one leukemia study G Growth arrest and apoptosis Especially relevant to leukemia models; dependency on functional p53 is not established across all cancers.
7 Chemosensitization and doxorubicin transport ↑ intracellular doxorubicin; ↑ doxorubicin cytotoxicity; ↓ Bcl-xL Not adequately established R/G Enhanced chemotherapy response Reported in breast cancer including multidrug-resistant cells and supported by animal combination experiments. This remains preclinical.
8 NR3C2 NFKBIZ NF-κB signaling ↑ NR3C2 stability; ↑ NFKBIZ; ↓ NF-κB signaling; ↓ proliferation; ↓ migration; ↓ invasion Not established G Growth and invasion suppression Recent gastric-cancer evidence supports direct interaction with NR3C2 and functional rescue experiments, but independent replication is needed.
9 PGK1 and PPAR signaling ↓ PGK1; ↑ PPARγ; ↓ proliferation; ↓ migration; ↓ invasion Not established G Metabolic and proliferative suppression Reported in breast-cancer models. PGK1 binding evidence includes computational methods supplemented by cellular validation; target assignment remains less mature than apoptosis or cell-cycle mechanisms.
10 NRF2 cytoprotective redox signaling Context-dependent ↑ NRF2/HO-1 and antioxidant defenses in several injury models R/G Normal-tissue protection Secondary mechanism. NRF2 activation is better supported for protection against oxidative tissue injury than for direct cancer-cell killing and therefore should not be treated as a universal anticancer NRF2 effect.
11 Migration and invasion ↓ migration; ↓ invasion (model-dependent) Not established G Reduced malignant phenotype Observed across selected lung, breast and gastric cancer models, often at concentrations substantially above measured human systemic exposure.
12 Clinical Translation Constraint Effective experimental concentrations frequently exceed achievable free systemic exposure Oxidation products can cause contact sensitization G Limits systemic anticancer translation Human 100 mg oral Cmax is approximately 85.5 ng/mL or 0.55 µM, whereas many cancer studies use approximately 10–1000+ µM. Formulation, local delivery and tumor exposure therefore remain major translational issues.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
Scientific Papers found: Click to Expand⟱
8322- LIN,  doxoR,    Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity
- vitro+vivo, Var, NA
ChemoSen↑, TumW↓, Na+↝,
8333- LIN,    Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors
- in-vitro, AML, NA
TumCG↓, Apoptosis↑, selectivity↑, P53↑, CC(CDKs/cyclins)↑,
8332- LIN,    Linalool decreases HepG2 viability by inhibiting mitochondrial complexes I and II, increasing reactive oxygen species and decreasing ATP and GSH levels
- in-vitro, Liver, HepG2 - in-vitro, Colon, Caco-2 - in-vitro, NA, NIH-3T3 - in-vitro, BC, MCF7 - in-vitro, Nor, HEK293
compI↓, compII↓, ATP↓, GSH↓, ROS↑,
8331- LIN,    Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model
- in-vivo, sarcoma, S180
ROS↑, *ROS↓, selectivity↑,
8330- LIN,    SIRT3-SOD2-ROS pathway is involved in linalool-induced glioma cell apoptotic death
- in-vitro, GBM, U87MG
tumCV↓, OCR↓, BAX↑, Bak↑, Bcl-2↓, Bcl-xL↓, Casp3↑, Casp9↑, Apoptosis↑, SOD↓, SIRT3↓, mt-ROS↑,
8329- LIN,    Microglial-targeting induced by intranasal linalool during neurological protection postischemia
- in-vivo, Stroke, NA - in-vivo, AD, NA
*Stroke↓, *BioAv↑, *neuroP↑, *motorD↑, *Learn↑, *COX2/PTGS2↓, *IL1β↓, *NRF2↑, *Dose↝, *cognitive↑,
8328- LIN,    Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway
- in-vitro, AML, NA
TumCG↓, selectivity?, p‑ERK↓, p‑JNK↑,
8327- LIN,    Recent updates on bioactive properties of linalool
- Review, Var, NA
*AntiCan↑, *AntiBio↑, *neuroP↑, *Stress↓, *hepatoP↑, *RenoP↑, *ROS↓, ROS↑, *Inflam↓, *toxicity↓, TumCP↓, TumCCA↑, mtDam↑, MMP↓, compI↓, compII↓, ETC↓, ATP↓, angioG↓, ChemoSen↑, *GSH↑, *MDA↓, *lipid-P↓, *NRF2↑, *HO-1↑, *ALAT↓, *AST↓, chemoP↑,
8326- LIN,    Linalool in cancer pharmacology: pharmacokinetic limitations and preclinical cytotoxic evidence for translational development
- Review, Var, NA
Dose↝, *BioAv↓, BioAv↝, tumCV↓, compI↓, compII↓, ROS↑, ATP↓, GSH↓, mtDam↑, Casp↑, NF-kB↓, MMP↓, TumCCA↑, PI3K↓, Akt↓, angioG↓, CD31/PECAM-1↓, Ki-67↓,
8325- LIN,    Validating linalool as a potential drug for breast cancer treatment based on machine learning and molecular docking
- in-vitro, BC, NA
tumCV↓, TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, TumCCA↑, PPARγ↑, PGK1↓,
8324- LIN,    Linalool targets NR3C2 to inhibit NF-κB-mediated gastric cancer progression
- vitro+vivo, GC, NA
TumCP↓, TumCMig↓, TumCI↓, NR3C2/MR↑, NR3C2/MR↑, NFKBIZ/IκBζ↓,
8323- LIN,  doxoR,    Efficacy of Combination Therapy with Linalool and Doxorubicin Encapsulated by Liposomes as a Two-in-One Hybrid Carrier System for Epithelial Ovarian Carcinoma
- vitro+vivo, Ovarian, NA
ChemoSen↑, TumCG↓, Ki-67↓, CD31/PECAM-1↓, Casp3↑, *toxicity↓, chemoP↑, *BioAv↓, EPR↑,
6464- LIN,  1,8-Cin,    Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells
- in-vitro, NSCLC, A549 - in-vitro, Nor, WI38
TumCP↓, TumCCA↑, selectivity↑, ROS↑, MMP↓, eff↓, TumCMig↓, Synergy↑,
8321- LIN,  doxoR,    Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells
- in-vitro, BC, MCF7
ChemoSen↑, EPR↑, Bcl-xL↓, P-gp/ABCB1↓, TumCCA⇅, tumCV↓, Apoptosis↑,
8320- LIN,    Ameliorative Effect of Linalool in Cisplatin-Induced Nephrotoxicity: The Role of HMGB1/TLR4/NF-κB and Nrf2/HO1 Pathways
- in-vivo, Nor, NA
RenoP↑, Dose↝, *TLR4↓, *MyD88↓, *TRIF↓, *TNF-α↓, *IL1β↓, *IL6↓, *NF-kB↓, *chemoP↑, *Casp3↓, *Casp9↓, *BAX↓, *Bcl-2↑, ChemoSen↑, *cardioP?, *hepatoP↑, *Apoptosis↓, *antiOx↑, *Inflam↓, *ROS↓, *BUN?, *creat↓, *GSH↑, *SOD↑, *Catalase↑, *MDA↓, *NADPH↓, *NRF2↑, *HO-1↑,
8319- LIN,    Linalool monoterpene exerts potent antitumor effects in OECM 1 human oral cancer cells by inducing sub-G1 cell cycle arrest, loss of mitochondrial membrane potential and inhibition of PI3K/AKT biochemical pathway
- in-vitro, Oral, OECM-1 - in-vitro, Nor, FR-2
tumCV?, selectivity↑, Apoptosis↑, TumCCA↑, p‑PI3K↓, p‑Akt↓, MMP↓,
8318- LIN,    Linalool Exhibits Cytotoxic Effects by Activating Antitumor Immunity
- in-vitro, BC, T47D - NA, CRC, SW-620 - NA, Liver, HepG2
TumCCA↑, IFN-γ↓, IL13↓, IL2↓, IL4↓, IL6↓, TNF-α↓, Th1 response?,
8317- LIN,    Linalool induces cell cycle arrest and apoptosis in HepG2 cells through oxidative stress generation and modulation of Ras/MAPK and Akt/mTOR pathways
- in-vitro, Liver, HepG2
TumCP↓, TumCCA↑, CDK4↓, cycA1/CCNA1↓, P21↑, p27/CDKN1B↑, Apoptosis↑, MMP↓, Casp3↑, cl‑PARP↑, DNAdam↑, RAS↓, Akt↓, mTOR↓, ROS↑, MAPK↑,
6484- LIN,    Linalool Inhibits MCF-7 Tumor Growth in a Xenograft Model by Apoptosis Induction and Immune Modulation
- vitro+vivo, BC, MCF7
TumCG↓, Apoptosis↑, ROS↓, TumCCA↑,
6483- LIN,    Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma
- in-vitro, Ovarian, A2780S
Apoptosis↑, ROS↑, MMP↓, Casp3↑, TumW↓, ChemoSen↑, EPR↑,
6482- LIN,    Pharmacological and molecular insights into linalool-rich Coriandrum sativum essential oil: Anticonvulsant, analgesic, anti-inflammatory, and antioxidant potential in rodent models
- Review, Nor, NA
IL1β↓, IL6↓, hepatoP↑, Inflam↓,
6481- LIN,    Linalool inhibits 22Rv1 prostate cancer cell proliferation and induces apoptosis
- in-vivo, Pca, 22Rv1
TumCP↓, Apoptosis↑, Ki-67↓, PCNA↓, TumCCA↑, MMP↓, TumCG↓,
6480- LIN,    Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs
- in-vitro, lymphoma, U937 - in-vitro, Var, HeLa
TumCD↑, TumCCA↑, P53↑, P21↑, p27/CDKN1B↑, p16↑, CDKN2C/p18↑,
6479- LIN,    Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer
- in-vivo, Colon, HCT116
Apoptosis↑, ROS↑, lipid-P↑, selectivity↑, TumCP↓, *toxicity↓,

Showing Research Papers: 1 to 24 of 24

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 24

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↓, 2,   lipid-P↑, 1,   ROS↓, 1,   ROS↑, 8,   mt-ROS↑, 1,   SOD↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

compI↓, 3,   compII↓, 3,   ETC↓, 1,   mtDam↑, 2,   OCR↓, 1,   SIRT3↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ATP↓, 3,   PGK1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 10,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 2,   Casp↑, 1,   Casp3↑, 4,   Casp9↑, 1,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 2,   p‑Akt↓, 1,   p‑ERK↓, 1,   p‑JNK↑, 1,   MAPK↑, 1,   mTOR↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   RAS↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV?, 1,   tumCV↓, 4,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   p16↑, 1,   P53↑, 2,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CC(CDKs/cyclins)↑, 1,   CDK4↓, 1,   CDKN2C/p18↑, 1,   cycA1/CCNA1↓, 1,   Ki-67↓, 3,   P21↑, 2,   p27/CDKN1B↑, 2,   TumCCA↑, 10,   TumCCA⇅, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Ki-67↓, 3,   TumCG↓, 5,   TumCP↓, 7,  

Migration(tgid=13) ⓘ

Na+↝, 1,   TumCI↓, 2,   TumCMig↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 2,   CD31/PECAM-1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

EPR↑, 3,   MMP↓, 7,   Na+↝, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IFN-γ↓, 1,   IL13↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL4↓, 1,   IL6↓, 2,   Inflam↓, 1,   NF-kB↓, 1,   NFKBIZ/IκBζ↓, 1,   Th1 response?, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

NR3C2/MR↑, 2,   PPARγ↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,   ChemoSen↑, 6,   Dose↝, 2,   eff↓, 1,   P-gp/ABCB1↓, 1,   selectivity?, 1,   selectivity↑, 5,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 2,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 2,   hepatoP↑, 1,   RenoP↑, 1,   TumW↓, 2,  
Total Targets: 85

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↑, 2,   HO-1↑, 2,   lipid-P↓, 1,   MDA↓, 2,   NRF2↑, 3,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   NADPH↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   Casp9↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL1β↓, 2,   IL6↓, 1,   Inflam↓, 2,   MyD88↓, 1,   NF-kB↓, 1,   TLR4↓, 1,   TNF-α↓, 1,   TRIF↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 1,   Dose↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BUN?, 1,   creat↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP?, 1,   chemoP↑, 1,   cognitive↑, 1,   hepatoP↑, 2,   Learn↑, 1,   motorD↑, 1,   neuroP↑, 2,   RenoP↑, 1,   Stress↓, 1,   Stroke↓, 1,   toxicity↓, 3,  

Infection & Microbiome(tgid=24) ⓘ

AntiBio↑, 1,  
Total Targets: 46

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#:410  Target#:%  State#:%  Dir#:%
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