Phenethyl isothiocyanate / NO 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)


NO, Nitric Oxide: Click to Expand ⟱
Source:
Type:
Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment.
Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS).

– In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer.

• Expression Patterns in Tumors:
– Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment.

– Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.


Scientific Papers found: Click to Expand⟱
4954- PEITC,    Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
- vitro+vivo, Ovarian, SKOV3
ROS↑, GSH↓, selectivity↑, mtDam↑, TumCD↑, OS↑, eff↑, *toxicity↓, H2O2↑, NO↑, eff↓, GPx↓, Dose↝, eff↑,
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 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GPx↓, 1,   GSH↓, 2,   H2O2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics

MMP↓, 1,   mtDam↑, 1,  

Cell Death

Apoptosis↑, 1,   Chk2↑, 1,   TumCD↑, 1,  

DNA Damage & Repair

ATM↑, 1,   DNAdam↑, 1,   P53↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

TumCG↓, 1,  

Angiogenesis & Vasculature

NO↑, 2,  

Drug Metabolism & Resistance

Dose↝, 1,   eff↓, 2,   eff↑, 2,   selectivity↑, 1,  

Functional Outcomes

OS↑, 1,  
Total Targets: 20

Pathway results for Effect on Normal Cells:


Functional Outcomes

toxicity↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: NO, Nitric Oxide
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#:563  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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