Phenethyl isothiocyanate / MMP 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)


MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱
Source:
Type:
Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.


Scientific Papers found: Click to Expand⟱
4918- PEITC,    Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights
- Review, Var, NA
Apoptosis↑, TumCP↓, angioG↓, TumMeta↓, NF-kB↓, Akt↓, MAPK↓, *BioAv↓, ROS↑, lipid-P↑, AIF↑, Cyt‑c↑, DR4↑, DR5↑, TumCCA↑, JAK↓, STAT3↓, MMP2↓, MMP9↓, PKCδ↓, Hif1a↓, JNK↓, Mcl-1↓, COX2↓, MMP↓, Casp3↑, ChemoSen↑, *BioAv↓, Half-Life↓,
4947- PEITC,    Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G0/G1   Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death
- in-vitro, Oral, HSC3
AntiCan↑, chemoPv↑, TumCG↓, Apoptosis↑, TumCCA↑, P53↑, P21↑, BAX↑, BID↑, Bcl-2↓, MMP↓, Cyt‑c↑, AIF↑, ROS↑, Ca+2↑,
4950- PEITC,    Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential
- vitro+vivo, Pca, PC3
MMP↓, Cyt‑c↑, Smad1↑, Diablo↑, ROS↑,
4956- PEITC,    Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells
- vitro+vivo, Lung, A549
GSH↓, ROS↑, mtDam↑, mitResp↓, MMP↓, CSCs↓, OCT4↓, ABC↓, SOX2↓, CD133↓, CD44↓, ALDH↓, Nanog↓, TumCG↓,
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↑,
4940- PEITC,    Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G 0/G 1 Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death
- in-vitro, Oral, HSC3
TumCCA↑, Apoptosis↑, BAX↑, BID↑, Bcl-2↓, MMP↓, Cyt‑c↑, AIF↑, tumCV↓, ROS↑, Ca+2↑, CDC25↓, CDK6↓, cycD1/CCND1↓, CDK2↓, cycE/CCNE↓, P53↑, p27↑, P21↑, Casp9↑, Casp3↑, GRP78/BiP↑,
4942- PEITC,    Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G(0)/G(1) Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death
- in-vitro, Oral, HSC3
chemoPv↑, TumCG↓, TumCCA↑, Apoptosis↑, BAX↑, BID↑, Bcl-2↓, MMP↓, Cyt‑c↑, AIF↑, ROS↑, Ca+2↑,
4944- PEITC,    Phenethyl isothiocyanate induces DNA damage-associated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations
- in-vitro, Oral, NA
TumCG↓, TumCCA↑, Apoptosis↑, ROS↑, NO↑, GSH↓, MMP↓, DNAdam↑, ATM↑, Chk2↑, P53↑, eff↓,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

CYP1A1↑, 1,   CYP2E1↑, 1,   GSH↓, 4,   lipid-P↑, 1,   ROS↑, 8,  

Mitochondria & Bioenergetics

AIF↑, 4,   ATP↓, 1,   CDC25↓, 1,   mitResp↓, 1,   MMP↓, 8,   mtDam↑, 1,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis

CYP3A4↓, 1,   Glycolysis↓, 1,  

Cell Death

Akt↓, 2,   Apoptosis↑, 6,   BAX↑, 3,   Bcl-2↓, 3,   BID↑, 3,   Casp3↑, 2,   Casp9↑, 1,   Chk2↑, 1,   Cyt‑c↑, 6,   Diablo↑, 1,   DR4↑, 2,   DR5↑, 1,   Fas↑, 1,   JNK↓, 1,   MAPK↓, 1,   Mcl-1↓, 1,   p27↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction

HER2/EBBR2↓, 1,  

Transcription & Epigenetics

other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

GRP78/BiP↑, 1,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

ATM↑, 1,   DNAdam↑, 1,   P53↑, 4,  

Cell Cycle & Senescence

CDK2↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State

ALDH↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   ERK↓, 1,   Nanog↓, 1,   OCT4↓, 1,   SOX2↓, 1,   STAT3↓, 1,   TumCG↓, 4,  

Migration

Ca+2↑, 3,   ITGB1↓, 1,   ITGB6↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   PKCδ↓, 1,   Smad1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 2,  

Angiogenesis & Vasculature

angioG↓, 2,   EGFR↓, 1,   Hif1a↓, 2,   NO↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   JAK↓, 1,   NF-kB↓, 2,  

Hormonal & Nuclear Receptors

CDK6↓, 1,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

EGFR↓, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes

AntiCan↑, 2,   chemoPv↑, 2,   Risk↓, 1,  
Total Targets: 93

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

Functional Outcomes

toxicity↝, 1,  
Total Targets: 11

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential
8 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#:197  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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