Phenethyl isothiocyanate / TumCI Cancer Research Results

PEITC, Phenethyl isothiocyanate: Click to Expand ⟱
Features:
Phenethyl isothiocyanate (PEITC) is a naturally occurring small-molecule phytochemical best known for its role in cancer chemoprevention research. It belongs to the isothiocyanate class of organosulfur compounds and has the chemical formula C₉H₉NS.
Source: Derived from glucosinolates in cruciferous vegetables
PEITC in plants exists mainly as the glucosinolate precursor (gluconasturtiin). Upon tissue disruption (chewing, chopping), myrosinase converts gluconasturtiin → PEITC.
-PEITC bioavailability from fresh, chopped microgreens is high
-Co-consumption with other isothiocyanates is additive/synergistic
-Peak plasma levels: ~1–3 hours post-consumption
-Half-life: ~4–6 hours
-Generally well tolerated up to 40 mg/day (mild GI irritation at higher dose)

PEITC is best characterized for its dual role in xenobiotic metabolism:
Inhibition of Phase I enzymes
-Suppresses cytochrome P450 enzymes (e.g., CYP1A1, CYP2E1)
-Reduces activation of pro-carcinogens

-Selectively depletes GSH in cancer cells
-Directly increases ROS beyond buffering capacity

Key pathways in cancer cells
-GSH depletion
-Mitochondrial ROS amplification
-ASK1/JNK apoptosis

Chemo relevance
-Frequently chemo-sensitizing
-Opposite of NAC/GSH

Induction of Phase II enzymes
-Activates NRF2–KEAP1 signaling
-Increases expression of detoxification and antioxidant enzymes such as:
 -Glutathione S-transferases (GSTs)
 -NAD(P)H quinone oxidoreductase 1 (NQO1)
 -Heme oxygenase-1 (HMOX1)

In preclinical systems, PEITC has been shown to:
-Deplete intracellular glutathione (GSH), increasing oxidative stress in cancer cells
-Induce mitochondrial dysfunction and apoptosis
-Inhibit histone deacetylases (HDACs) (context-dependent)
-Suppress pro-survival signaling pathways (e.g., STAT3, NF-κB)
-Target cancer stem–like cells in some models

Dietary origins

PEITC present in vegetables such as:
-Watercress (the richest source)
-Broccoli
-Cabbage
-Brussels sprouts
-Radish

Bioavailability depends on:
-Food preparation
-Gut microbiota (myrosinase activity if plant enzyme is inactive)

watercress microgreens generally have higher PEITC (and/or its precursor gluconasturtiin) per gram than mature watercress.
-The enrichment is most pronounced per unit fresh weight in the 7–14 day window.
-Absolute values vary substantially with cultivar, light intensity, sulfur/nitrogen nutrition, and post-harvest handling.
| Growth stage    |      Age | PEITC potential (mg / 100 g FW) |         Relative |
| --------------- | -------: | ------------------------------: | ---------------: |
| **Microgreens** |   7–10 d |                     **3.0–6.0** | **~2–4×** mature |
| **Microgreens** |  11–14 d |                     **2.5–5.0** |            ~2–3× |
| Baby leaf       |  21–28 d |                         1.5–3.0 |            ~1–2× |
| Mature leaf     | 35–45+ d |                         0.8–1.5 |         baseline |

Dry weight basis
| Growth stage          | PEITC potential (mg / g DW) |
| --------------------- | --------------------------: |
| Microgreens (7–10 d)  |                 **1.8–3.5** |
| Microgreens (11–14 d) |                     1.5–3.0 |
| Mature leaf           |                     0.6–1.2 |

Expect 2–5× variability depending on:
-Light spectrum (blue light ↑ glucosinolates)
-Sulfur availability

Practical optimization tips
Lighting
-12–16 h/day
-150–300 µmol/m²/s PAR (typical shop LEDs at 20–30 cm distance)
Soil
-Peat or peat-blend preferred
-Avoid over-watering (dilutes concentration)
Nutrition (optional but effective)
-One light watering with ¼-strength sulfate-containing fertilizer around day 4–5 can increase PEITC ~15–30%
Harvest & use
-Cut, rest 5–10 minutes, then consume (allows myrosinase to fully convert gluconasturtiin → PEITC)

Dose: (100 g fresh microgreens ≈ 2–4 mg bioavailable PEITC)
-ie below doses are not really acheivable from fresh microgreens
Minimum biologically active dose (humans): ~10–15 mg PEITC/day
Common efficacy range used in human trials: 20–40 mg/day
Upper short-term doses studied (generally tolerated): 60 mg/day
Diet-achievable with watercress microgreens: Yes, at realistic portions
These doses are chemopreventive / pathway-modulating, not cytotoxic chemotherapy.
| PEITC dose (mg/day) | Dominant biological effects                     |
| ------------------: | ----------------------------------------------- |
|         **5–10 mg** | Phase II enzymes, mild NRF2                     |
|        **10–20 mg** | HDAC inhibition, ROS signaling                  |
|        **20–40 mg** | Apoptosis, cell-cycle arrest, anti-inflammatory |
|        **40–60 mg** | Strong redox stress in cancer cells             |
|              >60 mg | Limited data; GI irritation risk                |



Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 GSH / thiol buffering (PEITC–GSH conjugation → GSH depletion) ↓ GSH Upstream redox collapse PEITC drives a GSH-iron-ROS axis; GSH depletion is upstream of multiple death programs (ref)
2 ROS accumulation ↑ ROS Oxidative stress trigger PEITC increases intracellular ROS, which then drives mitochondrial disruption and apoptosis (ref)
3 Ferroptosis (lipid peroxidation; anti-ferroptotic machinery overwhelmed) ↑ ferroptosis Iron-dependent oxidative death Direct evidence that PEITC induces ferroptosis (alongside other death programs) via GSH-iron-ROS mechanisms (ref)
4 Mitochondrial integrity (ΔΨm; cytochrome-c release) ↓ ΔΨm / ↑ cytochrome-c release Mitochondrial dysfunction PEITC promotes ROS, decreases ΔΨm, increases cytochrome-c release in cancer cells (ref)
5 Intrinsic apoptosis (caspase-9 → caspase-3) ↑ caspase activation / ↑ apoptosis Execution-phase cell death PEITC activates caspase-9 and caspase-3 and induces apoptosis downstream of mitochondrial dysfunction (ref)
6 Akt → JNK → Mcl-1 axis ↓ Akt / ↑ JNK / ↓ Mcl-1 Pro-survival signaling collapse Leukemia study: PEITC-initiated death is linked to Akt inactivation → JNK activation → Mcl-1 downregulation (ref)
7 NF-κB signaling ↓ NF-κB transcriptional activity / ↓ p65 nuclear translocation Reduced pro-survival / inflammatory transcription PEITC inhibits NF-κB activity and NF-κB–regulated genes (e.g., cyclin D1, VEGF, Bcl-xL) in prostate cancer cells (ref)
8 JAK–STAT3 signaling ↓ STAT3 activation Reduced survival / growth signaling PEITC inhibits IL-6–driven JAK–STAT3 activation in prostate cancer cells (STAT3 signaling direction shown) (ref)
9 Cell-cycle regulation ↑ G2/M arrest Proliferation blockade PEITC inhibits proliferation and induces G2/M cell-cycle arrest in prostate cancer cells (ref)
10 Autophagy program ↑ autophagy Stress response (can interact with death) PEITC induces autophagy along with ferroptosis and apoptosis in osteosarcoma cells (ref)
11 Migration / invasion (MMPs, FAK, RhoA) ↓ migration & invasion / ↓ MMPs Anti-metastatic phenotype PEITC suppresses migration/invasion and downregulates MMP-2/-7/-9 and motility regulators (FAK, RhoA) (ref)
12 In vivo anti-tumor effect ↓ tumor burden / ↑ survival (model-dependent) Demonstrated efficacy in animal model Leukemia study reports PEITC anti-leukemic activity including mechanistic signaling changes and in vivo efficacy evidence (ref)


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.


Scientific Papers found: Click to Expand⟱
4931- PEITC,    Phenethyl isothiocyanate (PEITC) suppresses prostate cancer cell invasion epigenetically through regulating microRNA-194
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
Risk↓, miR-194↑, TumCI↓, MMP2↓, MMP9↓, BMP2↓, *chemoPv↑,
4922- PEITC,    Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms
- Review, Var, NA
Risk↓, AntiCan↑, TumCP↓, TumMeta↓, ChemoSen↑, *BioAv↑, *other↝, *Dose↝, Dose↓, *BioAv↑, *Dose↝, *Half-Life↝, *toxicity↝, GSH↓, ROS↑, CYP1A1↑, CYP1A2↑, P450↓, CYP2E1↑, CYP3A4↓, CYP2A3/CYP2A6↓, *ROS↓, *GPx1↑, *SOD1↑, *SOD2↑, Akt↓, EGFR↓, HER2/EBBR2↓, P53↑, Telomerase↓, selectivity↑, MMP↓, Cyt‑c↑, Apoptosis↑, DR4↑, Fas↑, XIAP↓, survivin↓, TumAuto↑, Hif1a↓, angioG↓, MMPs↓, ERK↓, NF-kB↓, EMT↓, TumCI↓, TumCMig↓, Glycolysis↓, ATP↓, selectivity↑, *antiOx↑, Dose↝, other↝, OCR↓, GSH↓, ITGB1↓, ITGB6↓, ChemoSen↑,
4926- PEITC,    PEITC inhibits the invasion and migration of colorectal cancer cells by blocking TGF-β-induced EMT
- in-vitro, CRC, SW48
TumCI↓, TumCMig↓, EMT↓, Smad1↓, AntiCan↑, Snail↓, Slug↓, Zeb1↓, ZEB2↓, TGF-β1↓, eff↑, E-cadherin↑, N-cadherin↓, Vim↓,
4933- PEITC,    Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification
- vitro+vivo, Lung, H1299 - vitro+vivo, SCC, H226
AntiCan↓, TumCP↓, TumMeta↓, ChemoSen↑, tumCV↓, TumCI↓, TumCMig↓, FTO↓, TLE1↓, Akt↓, NF-kB↓,

Showing Research Papers: 1 to 4 of 4

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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

CYP1A1↑, 1,   CYP2E1↑, 1,   GSH↓, 2,   ROS↑, 1,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 1,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis

CYP3A4↓, 1,   Glycolysis↓, 1,  

Cell Death

Akt↓, 2,   Apoptosis↑, 1,   BMP2↓, 1,   Cyt‑c↑, 1,   DR4↑, 1,   Fas↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction

HER2/EBBR2↓, 1,  

Transcription & Epigenetics

other↝, 1,   TLE1↓, 1,   tumCV↓, 1,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

P53↑, 1,  

Proliferation, Differentiation & Cell State

EMT↓, 2,   ERK↓, 1,   miR-194↑, 1,  

Migration

E-cadherin↑, 1,   FTO↓, 1,   ITGB1↓, 1,   ITGB6↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   Smad1↓, 1,   Snail↓, 1,   TGF-β1↓, 1,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 2,   Vim↓, 1,   Zeb1↓, 1,   ZEB2↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 1,  

Immune & Inflammatory Signaling

NF-kB↓, 2,  

Drug Metabolism & Resistance

ChemoSen↑, 3,   CYP1A2↑, 1,   CYP2A3/CYP2A6↓, 1,   Dose↓, 1,   Dose↝, 1,   eff↑, 1,   P450↓, 1,   selectivity↑, 2,  

Clinical Biomarkers

EGFR↓, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes

AntiCan↓, 1,   AntiCan↑, 2,   Risk↓, 2,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   GPx1↑, 1,   ROS↓, 1,   SOD1↑, 1,   SOD2↑, 1,  

Transcription & Epigenetics

other↝, 1,  

Drug Metabolism & Resistance

BioAv↑, 2,   Dose↝, 2,   Half-Life↝, 1,  

Functional Outcomes

chemoPv↑, 1,   toxicity↝, 1,  
Total Targets: 11

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
4 Phenethyl isothiocyanate
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#:388  Target#:324  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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