Kaempferol / FOXO3 Cancer Research Results

KaempF, Kaempferol: Click to Expand ⟱
Features:

Kaempferol = dietary flavonol polyphenol (aglycone; often present as glycosides such as kaempferol-3-O-glucoside). Sources: tea, kale, spinach, capers, broccoli, onions. Primary mechanisms (ranked):
1) PI3K/Akt/mTOR pathway inhibition → ↓ proliferation, ↓ survival signaling (core anti-tumor axis).
2) MAPK modulation (ERK/JNK/p38) → apoptosis or growth arrest (context-dependent).
3) NF-κB suppression → ↓ inflammatory and pro-survival transcription programs.
4) Pro-oxidant ROS induction at higher concentrations → mitochondrial apoptosis signaling.
Bioavailability/PK relevance: Oral absorption modest; extensive phase II metabolism (glucuronidation/sulfation); plasma typically low µM or sub-µM after dietary intake; many in-vitro studies use 10–100 µM (often exceeding achievable systemic exposure without specialized delivery).
Clinical evidence status: largely preclinical (cell + animal); limited human cancer trial data; strongest support in epidemiologic associations rather than interventional oncology RCTs.

Kaempferol—an abundant flavonoid found in various fruits, vegetables, and medicinal herbs—affects cancer cell behavior

Pathways:
-Inhibit the PI3K/Akt signaling
-Modulation of the MAPK pathway (including ERK1/2)
-Inhibit NF-κB Signaling Pathway
-can upregulate or activate p53-dependent pathways
-Inhibitory action on STAT
-Activation of AMPK
-Reduce VEGF
-Can induce oxidative stress in cancer cells (ROS)

Kaempferol — Cancer vs Normal Pathway Effects

Rank Pathway / Axis Cancer Cells (↑ / ↓ / ↔) Normal Cells (↑ / ↓ / ↔) TSF Primary Effect Notes / Interpretation
1 PI3K/Akt/mTOR ↓ proliferation; ↓ survival signaling ↔ / mild ↓ (cytoprotective context) R→G Growth suppression Core mechanistic axis across multiple tumor models (breast, lung, colon, prostate).
2 MAPK (ERK, JNK, p38) ↑ JNK/p38 (pro-apoptotic); ↓ ERK (proliferative) ↔ (dose-dependent) R Apoptosis induction Often stress-activated signaling; balance of ERK vs JNK determines outcome.
3 NF-κB ↓ transcription of inflammatory & anti-apoptotic genes ↓ inflammatory tone R→G Anti-inflammatory / anti-survival Reduces cytokine signaling and tumor microenvironment support pathways.
4 ROS ↑ (high concentration; pro-oxidant apoptosis) ↔ / ↓ (antioxidant at low conc.) P→R Mitochondrial stress Biphasic: antioxidant at dietary levels; pro-oxidant at higher in-vitro doses.
5 NRF2 ↔ / ↓ (context-dependent) ↑ cytoprotective response G Redox adaptation May activate antioxidant genes in normal cells; persistent activation in tumors could support resistance.
6 Intrinsic apoptosis (Bax/Bcl-2, caspases) ↑ Bax; ↓ Bcl-2; ↑ caspase-3/9 ↔ R→G Mitochondrial apoptosis Common downstream convergence of ROS + PI3K suppression.
7 Ca2+ signaling ↑ mitochondrial Ca2+ (subset models) ↔ R Apoptotic amplification Not universal; observed in certain carcinoma lines.
8 HIF-1α / Angiogenesis ↓ HIF-1α; ↓ VEGF (model-dependent) ↔ G Anti-angiogenic potential Observed in hypoxia models; translational impact uncertain.
9 Ferroptosis ↔ (indirect; limited data) ↔ R Redox-linked sensitivity (theoretical) No consistent ferroptosis signature established.
10 Clinical Translation Constraint Low oral bioavailability; rapid conjugation; in-vitro concentrations commonly exceed systemic exposure; limited human interventional oncology data. — PK / Evidence Dietary intake likely below cytotoxic range; delivery systems (nano-formulations) under investigation.

TSF legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr
FOXO3, Forkhead Box O3: Click to Expand ⟱
Source:
Type:
FOXO3 (Forkhead Box O3) is a transcription factor that plays a critical role in regulating apoptosis, cell cycle arrest, DNA repair, and cellular stress responses.

• Positive Prognostic Marker
– In several cancers, higher nuclear FOXO3 expression (denoting active, transcriptionally functional FOXO3) is generally associated with a more favorable prognosis.
– Active FOXO3 can promote cell cycle arrest and apoptosis, thereby inhibiting tumor progression.

• Negative Prognostic Implications
– Conversely, reduced or cytoplasmically sequestered FOXO3 (often due to hyperactivation of the PI3K/Akt signaling pathway) has been linked to aggressive disease and poorer survival
 – Loss of FOXO3 function can allow tumor cells to proliferate unchecked and resist apoptosis, which contributes to a worse outcome.
Scientific Papers found: Click to Expand⟱
3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, TumCCA↓, HSPs↓, RAS↓, ROS↑, Ca+2↑, MMP↓, Cyt‑c↑, Endon↑, MMP9↓, MMP2↓, MMP7↓, MMP-10↓, VEGF↓, NF-kB↓, p65↓, iNOS↓, COX2↓, uPA↓, PI3K↓, FAK↓, MEK↓, ERK↓, JNK↓, p38↓, cJun↓, FOXO3↑,

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:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MEK↓, 1,   MMP↓, 1,  

Cell Death ⓘ

Cyt‑c↑, 1,   Endon↑, 1,   iNOS↓, 1,   JNK↓, 1,   p38↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,  

Protein Folding & ER Stress ⓘ

HSPs↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO3↑, 1,   PI3K↓, 1,   RAS↓, 1,  

Migration ⓘ

Ca+2↑, 1,   FAK↓, 1,   MMP-10↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   ROCK1↑, 1,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 1,   p65↓, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: FOXO3, Forkhead Box O3
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#:316  Target#:997  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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