Description: <b>Garlic</b> (Allium sativum L.) (active ingredient- Allicin, an active sulfer compound).<br>
<p><b>Allicin</b> — a reactive organosulfur thiosulfinate generated <i>in situ</i> when garlic (<i>Allium sativum</i>) tissue is crushed (alliin → allicin via alliinase). Functionally, it behaves as a short-lived electrophilic “reactive sulfur species” that rapidly modifies cellular thiols (e.g., glutathione and cysteine residues on proteins), producing broad redox and stress-signaling effects. Classification: small-molecule phytochemical (organosulfur thiosulfinate). Standard abbreviation(s): AL (common in Nestronics), “allicin”. Source/origin: freshly crushed raw garlic; allicin is not present in intact cloves and is chemically unstable, converting to other organosulfur metabolites after formation.</p>
<p><b>Primary mechanisms (ranked):</b></p>
<ol>
<li>Thiol reactivity and redox disruption: rapid GSH/protein-thiol modification (S-thioallylation), shifting redox buffering and triggering oxidative/electrophilic stress signaling.</li>
<li>Mitochondrial stress and intrinsic apoptosis (context-dependent): ΔΨm disruption, cytochrome-c release, caspase activation, ER stress/UPR engagement (often downstream of redox stress).</li>
<li>Inflammatory transcriptional suppression (context-dependent): inhibition of NF-κB–linked programs and, in some models, STAT3 signaling.</li>
<li>Acetate metabolism constraint (model-dependent): reversible inhibition of acetyl-CoA synthetase activity (ACS/ACSS), potentially impacting acetate→acetyl-CoA flux under metabolic stress.</li>
<li>Growth and invasion signaling attenuation (model-dependent): PI3K/AKT and MAPK network modulation with downstream effects on EMT/MMPs and angiogenic programs (e.g., HIF-1α/VEGF).</li>
</ol>
<p><b>Bioavailability / PK relevance:</b> “Allicin exposure” is dominated by formation conditions and rapid chemical/biologic turnover. Many oral preparations deliver alliin/alliinase that may generate allicin after ingestion; measured systemic allicin is typically transient, while downstream allyl-sulfur metabolites (e.g., allyl methyl sulfide–related products) are more detectable. Cooking/processing and GI conditions substantially change allicin bioequivalence versus crushed raw garlic.</p>
<p><b>In-vitro vs systemic exposure relevance:</b> Many anticancer cell studies use ~50–300 µM allicin; whether such free allicin concentrations are achievable at tumor sites after dietary/supplement intake is uncertain because of rapid thiol quenching and conversion to other sulfur species. Reported biological effects at lower concentrations may still occur locally (GI lumen/mucosa) or via metabolites, but direct extrapolation from high-µM in-vitro dosing is high-risk.</p>
<p><b>Clinical evidence status:</b> Predominantly preclinical (cell/animal) for anticancer mechanisms; human data are mixed and often evaluate garlic preparations rather than purified allicin, with outcomes confounded by formulation-dependent “allicin bioequivalence” and co-occurring organosulfur compounds (e.g., DADS/DATS/SAMC). Cancer-therapeutic evidence remains inconclusive.</p>
DADS (diallyl disulfide is a sulfur-based anticancer drug generated from garlic) <br>
Summary:<br>
- Four main organic sulfides in garlic, diallyl disulfide (DADS), diallyl trisulfide (DATS), S-allylmercaptocysteine (SAMC) and allicin.<br>
- Reversible inhibitor of ACSS2.<br>
- may inhibit NF-κB signaling<br>
- induce oxidative stress in cancer cells by generating ROS<br>
- might downregulate STAT3 activation<br>
- Inconclusive evidence for cancer treatment.<br>
- may inhibit <a href="tbResEdit.php?rid=2558">platelet aggregation</a><br>
Allicin is a reactive sulfur species (RSS) [23] with oxidizing properties, and it is able to oxidize thiols in cells, e.g., glutathione and cysteine residues in proteins.<br>
-Allicin is not present in intact garlic; rather, it is formed when garlic is chopped or crushed.
-Using crushed or chopped raw garlic or adding garlic at the end of the cooking process (after the heat is reduced) can help preserve its potential allicin content.<br>
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6073756/"> "Consumption of alliinase-inhibited cooked garlic was found to give higher than expected allicin bioequivalence, with AMS formation being about 30% (roasted garlic) or 16% (boiled garlic) that of crushed raw garlic."</a> <br>
<br>
-Allicin is not present in intact garlic.<br>
-It's formed enzymatically when alliin (a sulfur-containing amino acid) is converted by alliinase when garlic is chopped or crushed.Best consumed raw immediately after crushing (wait 5–10 min before consuming for full conversion)<br>
-Allicin is unstable, degrading within hours into other sulfur compounds (like diallyl disulfide).<br>
<br>
-Note <a href="tbResList.php?qv=27&tsv=1109&wNotes=on&exSp=open">half-life</a> reports vary 2.5-90hrs?.<br>
-moderately water-soluble but rapidly degrades/quenched (especially with thiols), so aqueous solutions have limited practical stability :
<a href="tbResList.php?qv=27&tsv=792&wNotes=on&exSp=open">BioAv</a>
<br><br>
<br>
Pathways:<br>
<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- induce
<a href="tbResList.php?qv=27&tsv=275&wNotes=on">ROS</a> production<br>
- ROS↑ related:
<a href="tbResList.php?&qv=27&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?&qv=27&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?&qv=27&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?&qv=27&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?&qv=27&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?&qv=27&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?&qv=27&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=HSP">HSP↓</a>
<br>
<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Lowers
<a href="tbResList.php?&qv=27&tsv=1103&wNotes=on&word=antiOx↓">AntiOxidant</a> defense in Cancer Cells:
<a href="tbResList.php?&qv=27&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?&qv=27&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<br>
- Raises
<a href="tbResList.php?&qv=27&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?&qv=27&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?&qv=27&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?&qv=27&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?&qv=27&tsv=46&wNotes=on&word=Catalase↑">Catalase↑</a>,
<br>
<!-- INFLAMMATION : NF-kB↓, COX2↓, COX2↓ PRO-INFL CYTOKINES: IL-1β↓, TNF-α↓, IL-6↓, IL-8↓, -->
- lowers
<a href="tbResList.php?&qv=27&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?&qv=27&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?&qv=27&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?&qv=27&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?&qv=27&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?&qv=27&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?&qv=27&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?&qv=27&tsv=368&wNotes=on&word=IL8↓">IL-8↓</a>
<br>
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.<br>
<!-- GROWTH/METASTASES : EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1, uPA↓, VEGF↓, ERK↓-->
- inhibit Growth/Metastases :
<a href="tbResList.php?&qv=27&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?&qv=27&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?&qv=27&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?&qv=27&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=27&tsv=105&wNotes=on">ERK↓</a>
<br>
<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=27&tsv=140&wNotes=on">HDAC↓</a>(not commonly listed as inhibitor),
<a href="tbResList.php?qv=27&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=27&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=HSP">HSP↓</a>
<br>
<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?&qv=27&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?&qv=27&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?&qv=27&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?&qv=27&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?&qv=27&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?&qv=27&tsv=895&wNotes=on">CDK6↓</a>,
<br>
<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?&qv=27&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?&qv=27&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=27&tsv=105&wNotes=on">ERK↓</a>,
<br>
<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=27&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=27&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=27&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=27&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<br>
<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- inhibits Cancer Stem Cells :
<a href="tbResList.php?qv=27&tsv=795&wNotes=on">CSC↓</a>,
<br>
<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=27&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=27&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=27&tsv=373&wNotes=on">STAT3</a>,
<a href="tbResList.php?qv=27&tsv=377&wNotes=on">Wnt↓</a>,
<a href="tbResList.php?qv=27&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=27&tsv=9&wNotes=on">AMPK↓</a>,
<a href="tbResList.php?qv=27&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=27&tsv=168&wNotes=on">JNK</a>,
<br>
<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=27&tsv=1106&wNotes=on&exSp=open">chemo-sensitization</a>,
<a href="tbResList.php?qv=27&tsv=1171&wNotes=on&exSp=open">chemoProtective</a>,
<a href="tbResList.php?qv=27&tsv=1107&wNotes=on&exSp=open">RadioSensitizer</a>,
<a href="tbResList.php?qv=27&tsv=1185&wNotes=on&exSp=open">RadioProtective</a>,
<a href="tbResList.php?qv=27&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=27&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=27&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=27&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=27&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=27&tsv=1188&wNotes=on">CardioProtective</a>,
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=27&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
<br>
<br>
Allicin has been reported to exhibit a range of effects, including:<br>
Antimicrobial activity: 10-50 μM<br>
Antioxidant activity: 10-100 μM<br>
Anti-inflammatory activity: 20-50 μM <br>
Anticancer activity: 50-100 μM or (50–300uM) (2–5 mg allicin per kilogram of body weight per day)<br>
Cardiovascular health: 20-50 μM<br>
<br>
Approximate μM concentrations of allicin that can be achieved:<br>
1 clove of garlic (3g): approximately 10-50 μM of allicin<br>
single clove of garlic may yield about 5–9 mg of allicin,<br>
1 tablespoon of minced garlic (15g): approximately 50-150 μM of allicin<br>
1 cup of chopped garlic (100g): approximately 200-500 μM of allicin<br>
1 tablespoon of chopped garlic chives (15g): approximately 5-20 μM of allicin<br>
1 cup of chopped garlic chives (100g): approximately 20-50 μM of allicin<br>
1 ounce (28g) of garlic microgreens: approximately 50-200 μM of allicin<br>
1 cup of garlic microgreens (100g): approximately 200-500 μM of allicin<br>
1 ounce (28g) of garlic chive microgreens: approximately 20-50 μM of allicin<br>
1 cup of garlic chive microgreens (100g): approximately 50-100 μM of allicin<br>
<br>
Allicin is a bioactive compound derived from garlic that has garnered significant interest for its potential anticancer properties through multiple mechanisms, including antioxidant activity, induction of apoptosis, cell cycle arrest, and modulation of key signaling pathways. While regular dietary intake of garlic is associated with cancer prevention benefits, allicin is also being explored as an adjunct to conventional cancer treatments. <br>
<br>
Available in supplement tablet/capsule form for example at 2000mg (fresh bulb equilvalent)<br>
IC50 of normal cells it >160mg/mL (large selectivity).<br>
IC50 might be about 12-30ug/ml (approximately 62-185 µM) (which is about 30-90 grams of garlic consumption).<br>
This makes it difficult to consume enough supplements to achieve that level.<br>
<br>
Pathways:<br>
<br>
ROS Generation and Oxidative Stress (inducing)<br>
• ROS generation is often considered a primary trigger that feeds into downstream pathways (e.g., MAPK activation, mitochondrial membrane permeabilization).<br>
Mitochondrial (Intrinsic) Apoptotic Pathway<br>
• ROS-induced mitochondrial damage can lead to the release of cytochrome c and subsequent activation of caspases (e.g., caspase-9 and caspase-3).<br>
NF-κB Signaling Inhibition (block)<br>
Modulation of MAPK Pathways (e.g., p38 MAPK and JNK)<br>
• ROS generation by allicin can activate stress-responsive kinases such as p38 MAPK and c-Jun N-terminal kinase (JNK).<br>
Inhibition of PI3K/Akt Pathway<br>
ROS levels and PI3K/Akt signaling, with increased oxidative stress often correlating with reduced Akt phosphorylation and activity.<br>
<br>
At lower doses, allicin may lead to a modest increase in ROS levels that the cell’s antioxidant defenses (e.g., glutathione, superoxide dismutase) can manage<br>
<br>
<h3>Allicin (Garlic) — mechanistic axes relevant to oncology</h3>
<table>
<thead>
<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>
</thead>
<tbody>
<tr>
<td>1</td>
<td>Thiol chemistry and redox buffering</td>
<td>GSH↓, protein thiols modified; ROS↑ (dose-dependent)</td>
<td>Adaptive buffering often stronger; ROS↔/↑ (context-dependent)</td>
<td>P</td>
<td>Electrophilic/thiol stress that re-wires signaling</td>
<td>Central “first-contact” mechanism: allicin rapidly reacts with cysteine/GSH, so many downstream pathway changes are secondary to thiol stress.</td>
</tr>
<tr>
<td>2</td>
<td>Mitochondria and intrinsic apoptosis</td>
<td>ΔΨm↓, Cyt-c↑, Caspase↑, cl-PARP↑</td>
<td>Typically less apoptosis at matched doses (selectivity varies)</td>
<td>R</td>
<td>Pro-apoptotic stress execution</td>
<td>Frequently downstream of rank #1; selectivity can reflect baseline redox fragility and metabolic state.</td>
</tr>
<tr>
<td>3</td>
<td>ER stress and UPR</td>
<td>ER stress↑, UPR↑ (model-dependent)</td>
<td>UPR↔/↑ (context-dependent)</td>
<td>R</td>
<td>Proteostasis stress amplification</td>
<td>Can couple to Ca²⁺ release, apoptosis, and inflammatory signaling changes.</td>
</tr>
<tr>
<td>4</td>
<td>Ca²⁺ signaling</td>
<td>Ca²⁺↑ (model-dependent)</td>
<td>Ca²⁺↔/↑ (context-dependent)</td>
<td>R</td>
<td>Stress coupling to mitochondria/ER</td>
<td>Often reported as part of the ER–mitochondria stress axis rather than a primary target.</td>
</tr>
<tr>
<td>5</td>
<td>NF-κB inflammatory axis</td>
<td>NF-κB↓; cytokine programs↓ (context-dependent)</td>
<td>Inflammatory tone↓ (context-dependent)</td>
<td>G</td>
<td>Anti-inflammatory transcriptional suppression</td>
<td>May be beneficial in tumor-promoting inflammation contexts; also relevant to platelet/vascular biology.</td>
</tr>
<tr>
<td>6</td>
<td>STAT3 signaling</td>
<td>STAT3↓ (model-dependent)</td>
<td>STAT3↔ (context-dependent)</td>
<td>G</td>
<td>Reduced survival/proliferation programs</td>
<td>Evidence is model-specific; frequently downstream of redox/inflammation modulation.</td>
</tr>
<tr>
<td>7</td>
<td>NRF2 antioxidant response</td>
<td>NRF2↓ or maladaptive NRF2 response (context-dependent)</td>
<td>NRF2↑ (context-dependent)</td>
<td>G</td>
<td>Differential stress adaptation</td>
<td>Reported “cancer vs normal” divergence is plausible but not universal; strongly dose/model dependent.</td>
</tr>
<tr>
<td>8</td>
<td>Acetate to acetyl-CoA metabolism</td>
<td>ACS/ACSS activity↓ (model-dependent)</td>
<td>ACS/ACSS activity↓ (context-dependent)</td>
<td>R</td>
<td>Limits acetate utilization under stress</td>
<td>Primary biochemical evidence exists for acetyl-CoA synthetase inhibition by allicin; translation to tumor-selective ACSS2 targeting is uncertain without exposure confirmation.</td>
</tr>
<tr>
<td>9</td>
<td>PI3K/AKT and MAPK network</td>
<td>PI3K/AKT↓, ERK/JNK↔/↓ (model-dependent)</td>
<td>↔ (context-dependent)</td>
<td>G</td>
<td>Reduced growth/survival signaling</td>
<td>Commonly reported but typically secondary to upstream stress/redox effects.</td>
</tr>
<tr>
<td>10</td>
<td>HIF-1α and angiogenesis</td>
<td>HIF-1α↓, VEGF↓ (model-dependent)</td>
<td>↔ (context-dependent)</td>
<td>G</td>
<td>Anti-angiogenic signaling shift</td>
<td>Most supportive data are preclinical; dependent on hypoxia models and dosing.</td>
</tr>
<tr>
<td>11</td>
<td>EMT, migration, invasion</td>
<td>EMT↓, MMPs↓ (model-dependent)</td>
<td>↔ (context-dependent)</td>
<td>G</td>
<td>Reduced invasive phenotype</td>
<td>Usually downstream of PI3K/MAPK/inflammation rewiring and/or oxidative stress–driven cytostasis.</td>
</tr>
<tr>
<td>12</td>
<td>Radiosensitization and chemosensitization</td>
<td>Sensitization↑ (context-dependent)</td>
<td>Protection↔/↑ (context-dependent)</td>
<td>G</td>
<td>Stress-based therapeutic interaction</td>
<td>Potential bidirectionality: pro-oxidant sensitization in tumors vs antioxidant adaptation in normal tissues depends on schedule and formulation.</td>
</tr>
<tr>
<td>13</td>
<td>Clinical Translation Constraint</td>
<td colspan="5">Chemical instability; rapid thiol quenching; formulation-dependent “allicin bioequivalence”; uncertain tumor-site free-allicin exposure; many in-vitro studies use high µM levels; human cancer outcomes largely from heterogeneous garlic preparations rather than purified allicin.</td>
<td>Primary constraint is exposure control, not target plausibility.</td>
</tr>
</tbody>
</table>