Kaempferol / uPA 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
uPA, Urokinase plasminogen activator: Click to Expand ⟱
Source:
Type:
uPA (urokinase plasminogen activator) is a serine protease that plays a crucial role in the conversion of plasminogen to plasmin, an enzyme responsible for degrading various components of the extracellular matrix (ECM). This activity is central to processes such as tissue remodeling, cell migration, and angiogenesis. In the context of cancer, uPA facilitates tumor invasion and metastasis by promoting ECM degradation, while its interaction with its receptor (uPAR) and inhibitors (such as PAI-1) forms a regulatory axis that is frequently dysregulated in malignancies.

Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS.

Elevated uPA expression has been observed in a broad range of cancers, including breast, colorectal, lung, and prostate cancers. These high levels are often indicative of increased proteolytic activity within the tumor microenvironment.
Tumors with aggressive behavior often exhibit upregulation of uPA, along with its receptor uPAR. This upregulation enhances plasmin generation and leads to an environment conducive to invasion and metastasis.

Elevated uPA levels in tumor tissues have been strongly associated with poor clinical outcomes. High uPA expression is correlated with increased risk of metastasis, higher likelihood of recurrence, and reduced overall survival in several cancer types.
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: uPA, Urokinase plasminogen activator
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#:428  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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