Description: <b>Crocetin</b> is a carotenoid pigment found in saffron (Crocus sativus) and has been studied for its potential anti-cancer properties. Research has shown that crocetin may have anti-tumor and anti-proliferative effects, inhibiting the growth of various types of cancer cells.<br>
Crocetin is a carotenoid dicarboxylic acid derived from saffron (Crocus sativus) and is a metabolite of crocin. It is lipophilic and more bioavailable than crocin. In cancer research, crocetin is studied mainly in preclinical models, where it appears to influence apoptosis, inflammation, angiogenesis, and redox signaling. It is not a primary cytotoxic chemotherapeutic, but a signaling and stress-modulating compound.<br>
<pre>
Mechanistic themes reported:
-NF-κB suppression
-PI3K/AKT pathway modulation
-MAPK signaling effects
-Apoptosis induction (mitochondrial pathway)
-Anti-angiogenic signaling (VEGF reduction)
-Redox modulation (context-dependent antioxidant / pro-oxidant behavior)
Evidence level: predominantly cell culture and animal models.
</pre>
Reported to modulate glycolytic metabolism and lactate production (model-dependent); not established as a direct LDH enzymatic inhibitor<br>
<br>
<b>Crocetin (Cro) — Cancer-Oriented Time-Scale Flagged Pathway Table</b>
<!-- Crocetin (Cro) — Cancer-Oriented Time-Scale Flagged Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>Bax ↑; Bcl-2 ↓; caspases ↑ (reported)</td>
<td>↔ (less activation)</td>
<td>G</td>
<td>Cell death signaling</td>
<td>Apoptosis induction via mitochondrial membrane disruption is one of the most frequently reported tumor effects.</td>
</tr>
<tr>
<td>2</td>
<td>NF-κB inflammatory signaling</td>
<td>NF-κB ↓; cytokines/COX-2 ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory modulation</td>
<td>Reduction of inflammatory transcription may contribute to anti-proliferative and anti-invasive effects.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K / AKT survival pathway</td>
<td>AKT phosphorylation ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth suppression</td>
<td>Observed in several tumor cell systems; should be presented as context-dependent.</td>
</tr>
<tr>
<td>4</td>
<td>MAPK signaling (ERK / JNK / p38)</td>
<td>Stress MAPK modulation (variable direction)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>JNK activation and ERK suppression have been reported in some models; effects vary by cell type.</td>
</tr>
<tr>
<td>5</td>
<td>ROS / redox modulation</td>
<td>ROS ↑ (pro-apoptotic) or ROS ↓ (antioxidant) depending on dose</td>
<td>Oxidative stress ↓ (protective models)</td>
<td>P, R, G</td>
<td>Redox modulation (biphasic)</td>
<td>Crocetin can behave as antioxidant in normal cells and pro-oxidant in tumor contexts at higher concentrations.</td>
</tr>
<tr>
<td>6</td>
<td>Cell-cycle arrest</td>
<td>G0/G1 or G2/M arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often secondary to survival pathway suppression and stress signaling.</td>
</tr>
<tr>
<td>7</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>VEGF ↓; angiogenic signaling ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Observed in some in vitro and animal tumor models; typically secondary to NF-κB/AKT changes.</td>
</tr>
<tr>
<td>8</td>
<td>Metabolic reprogramming (glycolysis tone)</td>
<td>Lactate ↓ (reported; indirect)</td>
<td>↔</td>
<td>R, G</td>
<td>Warburg modulation (indirect)</td>
<td>No strong evidence for direct LDH enzyme inhibition; effects likely secondary to survival/redox signaling changes.</td>
</tr>
<tr>
<td>9</td>
<td>Migration / invasion (MMPs)</td>
<td>MMP2/MMP9 ↓; invasion ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Reported reduction in metastasis markers in certain systems.</td>
</tr>
<tr>
<td>10</td>
<td>Chemo-sensitization (adjunct potential)</td>
<td>Therapy sensitivity ↑ (reported in some combinations)</td>
<td>Normal tissue protection possible</td>
<td>G</td>
<td>Adjunct modulation</td>
<td>May enhance cytotoxic response in some models; data are preclinical.</td>
</tr>
<tr>
<td>11</td>
<td>Translation constraint</td>
<td>Clinical anti-cancer efficacy not established</td>
<td>Generally well tolerated in dietary contexts</td>
<td>—</td>
<td>Evidence limitation</td>
<td>Human oncology data are limited; dosing and bioavailability remain practical considerations.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (early redox and signaling interactions)</li>
<li><b>R</b>: 30 min–3 hr (NF-κB / PI3K / MAPK modulation)</li>
<li><b>G</b>: >3 hr (apoptosis, angiogenesis, and phenotype-level outcomes)</li>
</ul>