Description: <b>Sodium Selenite</b> - is inorganic selenium in the selenite oxidation state (Se⁴⁺)<br>
Sodium selenite is produced industrially from selenium metal, which itself is obtained as a by-product of copper refining.<br>
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Mechanistic distinction from Selenium:
-Selenite reacts with GSH → GS–Se–SG intermediates
-Generates superoxide, H₂O₂
-Exploits cancer cells’ elevated basal oxidative stress
-Normal cells neutralize it more effectively (higher redox reserve)
Both the uptake and processing of selenium has recently shown to be upregulated in subsets of cancer cells
<a href="https://pubmed.ncbi.nlm.nih.gov/35101206/"> due to their increased expression of xCT transporter</a>
The more a tumor depends on xCT, the more toxic selenite becomes. High xCT Also Increases SSE Toxicity. High xCT increases intracellular thiols, which increases SSE chemical trapping, redox cycling, and cytotoxic impact.
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<br>
<a href="https://nestronics.ca/dbx/tbResEdit.php?rid=4434">Sodium selenite might protect against toxicity
of AgNPs.</a> also
<a href="https://nestronics.ca/dbx/tbResList.php?qv=149&qv2=153&wNotes=on">here</a><br>
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SSE and cancer
<table>
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>
<tr>
<td>1</td>
<td>Redox cycling with thiols (superoxide generation)</td>
<td>↑ O2•− / ↑ ROS</td>
<td>Acute oxidative stress</td>
<td>Defines sodium selenite anticancer mechanism in many models: early superoxide rise precedes mitochondrial apoptotic events</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2592502/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Glutathione buffering (GSH pool)</td>
<td>↓ GSH</td>
<td>Loss of redox buffering</td>
<td>Work in hepatoma models demonstrates GSH’s key role in selenite-driven oxidative stress and apoptosis</td>
<td><a href="https://www.sciencedirect.com/science/article/abs/pii/S0891584900002069" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓ ΔΨm</td>
<td>Mitochondrial dysfunction</td>
<td>Sequential mechanism shown: superoxide rise → mitochondrial depolarization</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2592502/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>4</td>
<td>Intrinsic apoptosis (cytochrome c → Caspase-9/3)</td>
<td>↑ cytochrome c release / ↑ Caspase-9/3</td>
<td>Programmed cell death</td>
<td>Same sequential model shows cytochrome c release followed by caspase-9 and caspase-3 activation</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2592502/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>ER stress / UPR (PERK → eIF2α → ATF4)</td>
<td>↑ PERK/eIF2α/ATF4</td>
<td>Proteotoxic stress signaling</td>
<td>ER-stress module is shown as a core driver in selenite-induced autophagy→apoptosis progression</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4047911/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Stress MAPK (p38) as switch control</td>
<td>↑ p38 activation</td>
<td>Signal switching (autophagy → apoptosis)</td>
<td>Mechanistic evidence for p38 participating in the selenite-driven transition toward apoptosis</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4047911/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>p53 activation (stress response)</td>
<td>↑ p53 phosphorylation (Ser15)</td>
<td>Facilitates apoptosis programs</td>
<td>NB4 leukemia model: selenite induces p53 Ser15 phosphorylation via p38/ERK in the autophagy–apoptosis switch context</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/25198662/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>DNA damage response (ATM-dependent signaling)</td>
<td>↑ ATM-dependent DDR</td>
<td>Checkpoint activation & death signaling</td>
<td>Selenium compounds (including selenite contexts) activate ATM-dependent DNA damage response signaling in colorectal cancer models</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20709753/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>9</td>
<td>PI3K–AKT axis linked to autophagy/apoptosis balance</td>
<td>↓ PI3K/Akt (functional axis) / ↓ protective autophagy</td>
<td>Apoptosis sensitization</td>
<td>NB4 leukemia: sodium selenite increases apoptosis by autophagy inhibition through PI3K/Akt</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/19788862/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>10</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB</td>
<td>Reduced anti-apoptotic transcription</td>
<td>Mechanistic study: sodium selenite induces ROS-mediated inhibition of NF-κB with downstream shift toward apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/30218457/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>11</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>↓ VEGF expression</td>
<td>Reduced vascular support signals</td>
<td>Prostate cancer PC3 model: sodium selenite inhibits expression of VEGF (and related inflammatory/pro-growth factors) in the tested context</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/19811770/" target="_blank">(ref)</a></td>
</tr>
<tr>
<td>12</td>
<td>Ferroptosis (iron-dependent oxidative death)</td>
<td>↑ ferroptosis</td>
<td>Non-apoptotic oxidative death modality</td>
<td>Paper explicitly reports sodium selenite as an inducer of ferroptosis across multiple human cancer cell types</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7453065/" target="_blank">(ref)</a></td>
</tr>
</table>
<br>
Table to compare Sodium Selenite to SeNPs<br>
-Sodium selenite → chemical oxidant (thiol attack → ROS shock).<br>
-SeNPs → engineered redox stressor (signaling-level control, broader window).<br>
-Selenomethionine / Se-yeast → redox buffer & selenium storage form (often protective to cancer cells, especially when oxidative stress is a therapeutic goal).<br>
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Dimension</th>
<th>Sodium Selenite (Na2SeO3)</th>
<th>Selenium Nanoparticles (SeNPs)</th>
<th>Selenomethionine / Se-Yeast</th>
</tr>
<tr>
<td>Primary mechanistic class</td>
<td>Direct redox-disrupting agent</td>
<td>Controlled redox modulator / signaling perturbator</td>
<td>Nutritional selenium reservoir / selenoprotein precursor</td>
</tr>
<tr>
<td>Initial molecular interaction</td>
<td>Rapid reaction with cellular thiols (GSH, Trx, protein –SH)</td>
<td>Cellular uptake → gradual selenium release or surface redox effects</td>
<td>Nonspecific incorporation into proteins in place of methionine</td>
</tr>
<tr>
<td>ROS generation</td>
<td>↑↑ acute, non-buffered ROS burst</td>
<td>↑ mild–moderate, sustained ROS</td>
<td>↓ or ↔ (antioxidant bias)</td>
</tr>
<tr>
<td>Glutathione (GSH) system</td>
<td>↓↓ GSH depletion</td>
<td>↔ or mild ↓ (context-dependent)</td>
<td>↑ GSH recycling via GPX support</td>
</tr>
<tr>
<td>Redox selectivity (cancer vs normal)</td>
<td>Limited; toxicity threshold close to efficacy</td>
<td>Improved tumor selectivity window</td>
<td>Poor for cancer killing; favors normal-cell protection</td>
</tr>
<tr>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓↓ rapid depolarization</td>
<td>↓ gradual, dose-dependent disruption</td>
<td>↔ or ↑ mitochondrial protection</td>
</tr>
<tr>
<td>Dominant cell-death pathways</td>
<td>Intrinsic apoptosis ± necrosis (high dose)</td>
<td>Apoptosis ± ferroptosis ± autophagy-related death</td>
<td>None (cytoprotective)</td>
</tr>
<tr>
<td>ER stress / UPR (PERK–CHOP)</td>
<td>↑ strong, early activation</td>
<td>↑ moderate, delayed activation</td>
<td>↓ ER stress via antioxidant capacity</td>
</tr>
<tr>
<td>DNA damage response</td>
<td>↑ oxidative DNA lesions (ATM/ATR)</td>
<td>↑ low–moderate, secondary to ROS</td>
<td>↓ DNA damage; improved repair environment</td>
</tr>
<tr>
<td>PI3K–AKT survival signaling</td>
<td>↓ secondary to oxidative collapse</td>
<td>↓ reported in multiple tumor models</td>
<td>↔ or ↑ survival signaling</td>
</tr>
<tr>
<td>NF-κB / inflammatory signaling</td>
<td>↓ via redox inhibition</td>
<td>↓ selectively; anti-inflammatory bias</td>
<td>↓ chronic inflammation (protective)</td>
</tr>
<tr>
<td>Ferroptosis involvement</td>
<td>Minor / indirect</td>
<td>↑ lipid peroxidation; GPX4 modulation</td>
<td>↓↓ ferroptosis risk (GPX4 support)</td>
</tr>
<tr>
<td>Autophagy</td>
<td>↑ early (protective) → collapse</td>
<td>↑ contributory to tumor suppression</td>
<td>↔ homeostatic maintenance</td>
</tr>
<tr>
<td>Angiogenesis (VEGF)</td>
<td>↓ at cytotoxic doses</td>
<td>↓ at lower, tolerated doses</td>
<td>↔ or mild ↓ (indirect)</td>
</tr>
<tr>
<td>Immune compatibility</td>
<td>Poor at anticancer doses</td>
<td>Moderate–good; often immune-supportive</td>
<td>High; supports immune competence</td>
</tr>
<tr>
<td>Pharmacologic control</td>
<td>Poor (steep dose–toxicity curve)</td>
<td>High (size, coating, release tunable)</td>
<td>Low (slow turnover, storage form)</td>
</tr>
<tr>
<td>Normal tissue tolerance</td>
<td>Low</td>
<td>Moderate–high</td>
<td>High</td>
</tr>
<tr>
<td>Overall cancer relevance</td>
<td>Potent but hazardous cytotoxic agent</td>
<td>Balanced anticancer redox modulator</td>
<td>Generally counterproductive for direct cancer killing</td>
</tr>
<tr>
<td>Overall therapeutic profile</td>
<td>Potent but narrow safety margin</td>
<td>Lower acute potency, broader usable window</td>
</tr>
</table>