Phenethyl isothiocyanate / p65 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)


p65, RelA: Click to Expand ⟱
Source:
Type:
P65, also known as RelA, is a subunit of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factor complex. NF-κB plays a crucial role in regulating immune response, inflammation, and cell survival.
Due to its role in cancer progression, p65 and the NF-κB pathway are considered potential therapeutic targets. Inhibitors of NF-κB signaling are being explored in preclinical and clinical studies as potential cancer treatments.
Many studies have reported that p65 is overexpressed in various types of cancers, including breast, prostate, lung, and colorectal cancers.
In some cancers, elevated p65 levels correlate with higher grades of tumors and advanced stages of disease.

"RELA proto-oncogene, NF-κB subunit." It encodes the p65 protein, which is a central component of the NF‑κB transcription factor complex.
-Chronic activation of RELA and the NF‑κB pathway is frequently associated with cancer progression, promoting inflammation-driven tumorigenesis, chemoresistance, and metastasis.
-RELA interacts with other oncogenic signaling networks (for example, STAT3 and MAPK pathways), further integrating environmental signals that favor cancer progression.

RELA (p65) is a critical subunit of the NF‑κB transcription factor complex, involved in the regulation of genes that control inflammation, cell survival, and proliferation. In the context of cancer, aberrant activation and overexpression of RELA are frequently associated with aggressive tumor behavior, therapy resistance, and poorer patient outcomes in cancers such as breast, lung, colorectal, and pancreatic cancers, among others.

RELA emerges as a potential key contributor to the suppression of glycolysis, mitochondrial respiration, and ATP production in cancer cells. (RELA knockdown signifcantly reduced the tumorigenic.
potential of various pancreatic cancer cell lines).


Scientific Papers found: Click to Expand⟱
5185- PEITC,  SFN,    Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells
- in-vitro, Pca, PC3
NF-kB↓, p65↓, VEGF↓, cycD1/CCND1↓, Bcl-xL↓, IKKα↓,

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:


Cell Death

Bcl-xL↓, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Immune & Inflammatory Signaling

IKKα↓, 1,   NF-kB↓, 1,   p65↓, 1,  
Total Targets: 6

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: p65, RelA
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#:238  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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