tbResList Print — KaempF Kaempferol

Description: <p><b>Kaempferol</b> = dietary flavonol polyphenol (aglycone; often present as glycosides such as kaempferol-3-O-glucoside). Sources: tea, kale, spinach, capers, broccoli, onions. Primary mechanisms (ranked):<br>
1) <b>PI3K/Akt/mTOR pathway inhibition</b> → ↓ proliferation, ↓ survival signaling (core anti-tumor axis).<br>
2) <b>MAPK modulation (ERK/JNK/p38)</b> → apoptosis or growth arrest (context-dependent).<br>
3) <b>NF-κB suppression</b> → ↓ inflammatory and pro-survival transcription programs.<br>
4) <b>Pro-oxidant ROS induction at higher concentrations</b> → mitochondrial apoptosis signaling.<br>
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).<br>
Clinical evidence status: largely <b>preclinical</b> (cell + animal); limited human cancer trial data; strongest support in epidemiologic associations rather than interventional oncology RCTs.</p>


<b>Kaempferol</b>—an abundant flavonoid found in various fruits, vegetables, and medicinal herbs—affects cancer cell behavior<br>
<br>
Pathways:<br>
-Inhibit the PI3K/Akt signaling<br>
-Modulation of the MAPK pathway (including ERK1/2) <br>
-Inhibit NF-κB Signaling Pathway<br>
-can upregulate or activate p53-dependent pathways<br>
-Inhibitory action on STAT<br>
-Activation of AMPK<br>
-Reduce VEGF<br>
-Can induce oxidative stress in cancer cells (ROS)<br>



<br>
<h3>Kaempferol — Cancer vs Normal Pathway Effects</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells (↑ / ↓ / ↔)</th>
<th>Normal Cells (↑ / ↓ / ↔)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>

<tr>
<td>1</td>
<td>PI3K/Akt/mTOR</td>
<td>↓ proliferation; ↓ survival signaling</td>
<td>↔ / mild ↓ (cytoprotective context)</td>
<td>R→G</td>
<td>Growth suppression</td>
<td>Core mechanistic axis across multiple tumor models (breast, lung, colon, prostate).</td>
</tr>

<tr>
<td>2</td>
<td>MAPK (ERK, JNK, p38)</td>
<td>↑ JNK/p38 (pro-apoptotic); ↓ ERK (proliferative)</td>
<td>↔ (dose-dependent)</td>
<td>R</td>
<td>Apoptosis induction</td>
<td>Often stress-activated signaling; balance of ERK vs JNK determines outcome.</td>
</tr>

<tr>
<td>3</td>
<td>NF-κB</td>
<td>↓ transcription of inflammatory &amp; anti-apoptotic genes</td>
<td>↓ inflammatory tone</td>
<td>R→G</td>
<td>Anti-inflammatory / anti-survival</td>
<td>Reduces cytokine signaling and tumor microenvironment support pathways.</td>
</tr>

<tr>
<td>4</td>
<td>ROS</td>
<td>↑ (high concentration; pro-oxidant apoptosis)</td>
<td>↔ / ↓ (antioxidant at low conc.)</td>
<td>P→R</td>
<td>Mitochondrial stress</td>
<td>Biphasic: antioxidant at dietary levels; pro-oxidant at higher in-vitro doses.</td>
</tr>

<tr>
<td>5</td>
<td>NRF2</td>
<td>↔ / ↓ (context-dependent)</td>
<td>↑ cytoprotective response</td>
<td>G</td>
<td>Redox adaptation</td>
<td>May activate antioxidant genes in normal cells; persistent activation in tumors could support resistance.</td>
</tr>

<tr>
<td>6</td>
<td>Intrinsic apoptosis (Bax/Bcl-2, caspases)</td>
<td>↑ Bax; ↓ Bcl-2; ↑ caspase-3/9</td>
<td>↔</td>
<td>R→G</td>
<td>Mitochondrial apoptosis</td>
<td>Common downstream convergence of ROS + PI3K suppression.</td>
</tr>

<tr>
<td>7</td>
<td>Ca²⁺ signaling</td>
<td>↑ mitochondrial Ca²⁺ (subset models)</td>
<td>↔</td>
<td>R</td>
<td>Apoptotic amplification</td>
<td>Not universal; observed in certain carcinoma lines.</td>
</tr>

<tr>
<td>8</td>
<td>HIF-1α / Angiogenesis</td>
<td>↓ HIF-1α; ↓ VEGF (model-dependent)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic potential</td>
<td>Observed in hypoxia models; translational impact uncertain.</td>
</tr>

<tr>
<td>9</td>
<td>Ferroptosis</td>
<td>↔ (indirect; limited data)</td>
<td>↔</td>
<td>R</td>
<td>Redox-linked sensitivity (theoretical)</td>
<td>No consistent ferroptosis signature established.</td>
</tr>

<tr>
<td>10</td>
<td><b>Clinical Translation Constraint</b></td>
<td colspan="2">Low oral bioavailability; rapid conjugation; in-vitro concentrations commonly exceed systemic exposure; limited human interventional oncology data.</td>
<td>—</td>
<td>PK / Evidence</td>
<td>Dietary intake likely below cytotoxic range; delivery systems (nano-formulations) under investigation.</td>
</tr>

</table>

<p><b>TSF legend:</b> P: 0–30 min | R: 30 min–3 hr | G: &gt;3 hr</p>