Lemongrass Extract/Citral / eIF2α Cancer Research Results

LGE, Lemongrass Extract/Citral: Click to Expand ⟱
Features:
lemongrass extract/ Cymbopogon citratus / lemongrass essential oil

Promising in vitro and limited animal anticancer evidence, especially via ROS-mediated apoptosis and mitochondrial/cell-cycle effects. Citral likely is main active ingredient.

Lemongrass Extract/Citral — Lemongrass preparations are derived principally from the leaves of Cymbopogon citratus and may be prepared as aqueous or ethanolic extracts or as volatile essential oil. Citral (CIT) is an acyclic monoterpene aldehyde and is usually the dominant constituent of lemongrass essential oil; chemically, citral is a mixture of the geometric isomers geranial (citral A) and neral (citral B). The database abbreviation LGE is appropriate for lemongrass extract, while CIT is preferable when the isolated compound is specifically studied. Essential-oil preparations can contain roughly 60–80% citral, but composition varies substantially with cultivar, plant tissue, extraction method, and geographic origin. Whole aqueous or ethanolic lemongrass extracts are not pharmacologically equivalent to purified citral because they contain additional terpenes and nonvolatile phytochemicals.

Primary mechanisms (ranked):

  1. ROS accumulation and oxidative stress in cancer cells, producing DNA damage and triggering mitochondrial apoptosis.
  2. Mitochondrial apoptotic signaling through ↓ mitochondrial membrane potential, ↑ Bax, ↓ Bcl-2/Bcl-xL, and ↑ caspase-3 activation; p53-dependent signaling is important in several models.
  3. ALDH1A3 inhibition, potentially suppressing cancer stem-cell phenotype, clonogenicity, retinoic-acid-linked transcription, and chemotherapy resistance.
  4. Microtubule disruption through inhibition of tubulin polymerization together with MARK4 inhibition, producing antiproliferative and cell-cycle effects.
  5. Suppression of proliferative and survival signaling including AKT, ERK1/2, and NF-κB in selected cancer models.
  6. Cell-cycle arrest, commonly G0/G1 or G1/S depending on model and preparation.
  7. Endoplasmic-reticulum stress and stress-associated autophagy in some p53-deficient cancer cells.
  8. Chemosensitization, including enhanced effects of doxorubicin, docetaxel, FOLFOX-associated drugs, paclitaxel, and other cytotoxics in preclinical models; transporter effects including MDR1/MRP1/BCRP suppression have been reported.

Bioavailability / PK relevance: Citral is lipophilic, volatile, chemically unstable, and rapidly metabolized. Animal disposition studies indicate extensive gastrointestinal absorption but rapid conversion to oxidized, reduced, and conjugated metabolites, with little persistence of unchanged citral in circulation and predominantly urinary elimination of metabolites. Thus, good absorption does not imply high systemic exposure to intact citral. Encapsulation with polymers, cyclodextrins, lipid systems, or nanoparticles has been investigated to improve stability and effective exposure. Human pharmacokinetic data defining circulating intact citral after therapeutic oral dosing remain limited.

In-vitro vs systemic exposure relevance: Many anticancer experiments use citral concentrations in the tens to hundreds of micromolar range, commonly about 20–200 µM, or relatively concentrated lemongrass extracts. These exposures cannot presently be assumed to be attainable as sustained concentrations of intact citral in human plasma after tea, food, or conventional oral supplementation because parent citral undergoes very rapid metabolism. Whole-extract studies also cannot be quantitatively translated into equivalent systemic citral exposure. Consequently, the strongest mechanistic findings should be considered preclinical and concentration-dependent.

Clinical evidence status: Preclinical. Anticancer activity is supported by numerous cancer-cell studies and several animal xenograft experiments using citral or lemongrass extracts. Chemosensitization is also preclinical. Human studies of lemongrass tea and topical essential oil provide limited tolerability and non-oncology clinical information, but there is no established human anticancer efficacy and no approved oncology indication for citral or lemongrass extract. Citral is permitted as a food flavoring agent and is listed by the FDA under food-use regulations; this regulatory status does not establish therapeutic anticancer efficacy. Safety is concentration- and formulation-dependent: concentrated citral and essential oils can be cytotoxic or genotoxic in cultured normal cells, while some cancer models demonstrate relative tumor-cell selectivity.

Mechanistic Effects of Lemongrass Extract and Citral

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS and oxidative stress ↑ ROS, ↓ GSH ↔ or ↑ ROS (dose-dependent) R Oxidative damage and apoptosis One of the best-supported anticancer mechanisms of citral and lemongrass preparations. ROS elevation precedes mitochondrial dysfunction in several cancer models; antioxidant effects can occur in non-cancer systems, making modulation context-dependent.
2 Mitochondrial apoptosis ↓ membrane potential, ↑ Bax, ↓ Bcl-2, ↓ Bcl-xL, ↑ caspase-3 ↔ or weaker effect (model-dependent) R/G Intrinsic apoptosis Demonstrated in colorectal, leukemia, breast, ovarian, and other cancer models. ROS frequently acts upstream of mitochondrial depolarization.
3 ALDH1A3 and cancer stem cells ↓ ALDH1A3 activity Not established R/G ↓ clonogenicity and stem-cell-associated tumor growth Citral directly inhibits ALDH1A3-associated activity and reduced growth of ALDH1A3-driven breast tumor models. Potential relevance to cancer stem cells and drug resistance.
4 Tubulin and microtubules ↓ tubulin polymerization, ↑ microtubule depolymerization ↓ (high concentration or exposure-dependent) P/R Microtubule disruption and proliferation inhibition Citral can directly disrupt microtubules and inhibit polymerization. This is not inherently cancer-selective and is therefore an efficacy and toxicity mechanism.
5 MARK4 ↓ MARK4 Not established R Antiproliferative signaling and microtubule regulation Biochemical binding and kinase inhibition studies support MARK4 as a direct citral target associated with its microtubule-related activity.
6 p53 apoptotic signaling ↑ p53 phosphorylation and activity Not established R/G ↑ Bax, PUMA, NOXA and apoptosis ROS-dependent p53 activation contributes strongly to apoptosis in p53-competent cells. p53-deficient cells may instead depend more heavily on ER-stress mechanisms.
7 AKT and PI3K survival signaling ↓ AKT, ↓ PI3K signaling Not established R/G Reduced survival and proliferation Reported particularly in melanoma and other cancer-cell systems; importance varies by cancer type.
8 ERK signaling ↓ ERK1/2 Not established R/G Reduced proliferative signaling Observed alongside AKT suppression and oxidative stress in melanoma models.
9 NF-κB survival signaling ↓ NF-κB Context-dependent R/G Reduced prosurvival and inflammatory signaling NF-κB suppression has been reported in melanoma and leukemia models and may contribute to apoptosis.
10 Cell cycle ↑ G0/G1 or G1/S arrest ↔ or less affected (model-dependent) G ↓ proliferation Phase of arrest varies with cell type, citral concentration, and whether purified citral or whole lemongrass extract is used.
11 Endoplasmic reticulum stress ↑ CHOP, ↑ ATF4, ↑ phospho-eIF2α, ↑ GADD45 Not established R/G Stress-associated growth inhibition and apoptosis Especially relevant in p53-deficient models where ER stress may compensate for reduced p53-mediated apoptotic signaling.
12 Autophagy ↑ (context-dependent) Not established G Stress response contributing to cytotoxicity Autophagy-associated proteins including ATG5 have been altered after citral treatment; whether autophagy is lethal or adaptive is model-dependent.
13 Chemosensitization ↑ Potential toxicity sparing in selected models G Enhanced chemotherapy response Lemongrass extract or citral has enhanced responses to FOLFOX-associated drugs, paclitaxel, docetaxel, doxorubicin, and other agents in preclinical studies. Clinical confirmation is absent.
14 Drug efflux and multidrug resistance ↓ MDR1, ↓ MRP1, ↓ BCRP, ↑ intracellular doxorubicin Not established G Reduced multidrug resistance Lemongrass oil and citral increased doxorubicin accumulation in resistant cancer-cell models. Whole oil and purified citral are not necessarily equivalent.
15 Drug metabolism signaling ↓ PXR, ↓ CYP3A4, ↓ GST (model-dependent) Drug-metabolizing enzymes can also be altered G Potential alteration of chemotherapy disposition Potentially contributes to chemosensitization but also raises a possible drug-interaction concern. Rat studies demonstrate modulation of hepatic xenobiotic-metabolizing enzymes at high citral or lemongrass-oil doses.
16 Clinical Translation Constraint Preclinical activity Limited selectivity at sufficiently high exposure G Low parent-drug exposure and uncertain therapeutic window Citral is rapidly metabolized, volatile, and chemically unstable. Many effective in-vitro concentrations likely exceed sustained systemic concentrations of intact citral achievable through ordinary oral intake. Nanoparticle and other delivery systems improve experimental exposure but are not established cancer treatments.

TSF: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
eIF2α, Eukaryotic translation initiation factor 2: Click to Expand ⟱
Source:
Type:
The phosphorylation of eIF2α is carried out by a family of four kinases, PERK (PKR-like ER kinase), PKR (protein kinase double-stranded RNA-dependent), GCN2 (general control non-derepressible-2), and HRI (heme-regulated inhibitor).
Eukaryotic translation initiation factor 2 alpha (eIF2α) is a critical protein involved in the initiation of protein synthesis in eukaryotic cells. It plays a key role in regulating translation in response to various cellular stresses, including nutrient deprivation, oxidative stress, and viral infection. The phosphorylation status of eIF2α is particularly important, as it can influence cell survival, apoptosis, and the overall stress response.

The phosphorylation status of eIF2α can have significant prognostic implications in cancer. Elevated levels of phosphorylated eIF2α are often associated with poor prognosis in several cancer types, as they may indicate a tumor's ability to adapt to stress and survive in unfavorable conditions.
Scientific Papers found: Click to Expand⟱
8187- LGE,    Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation
- in-vitro, BC, 4T1 - in-vitro, Ovarian, OVCAR-3 - in-vitro, Ovarian, SKOV3
TumCP↓, TumCCA↑, Apoptosis↑, cl‑Casp3↑, BAX↑, Bcl-2↓, ER Stress↑, CHOP/DDIT3↑, GADD45A↑, EDEM↑, ATF4↑, HSP90↑, ATG5↑, eIF2α↑, ROS↑, P53↑, eff↓,

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:


NA, unassigned(tgid=0) ⓘ

EDEM↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   cl‑Casp3↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   eIF2α↑, 1,   ER Stress↑, 1,   HSP90↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

GADD45A↑, 1,   P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Migration(tgid=13) ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↓, 1,  
Total Targets: 17

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: eIF2α, Eukaryotic translation initiation factor 2
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#:398  Target#:509  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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