Kaempferol / Ca+2 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
Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
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: Ca+2, Calcium Ion Ca+2
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#:38  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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