tbResList Print — CAP Capsaicin

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CAP Capsaicin
Description: <b>Capsaicin </b>is a chemical compound that gives chili peppers their spicy flavor and heat.<br>
<br>
Biological activity, capsaicin has been reported to exhibit a range of effects, including:<br>
Pain relief: 10-50 μM<br>
Anti-inflammatory activity: 20-50 μM<br>
Antioxidant activity: 10-100 μM<br>
Anti-cancer activity: 50-100 μM<br>
Cardiovascular health: 20-50 μM<br>
<br>
Approximate μM concentrations of capsaicin, the active compound in chili peppers, that can be achieved with different amounts of chili peppers:<br>
1 teaspoon of dried chili pepper flakes (5g):~10-50 μM of capsaicin<br>
1 tablespoon of dried chili pepper flakes (15g): ~30-150 μM of capsaicin<br>
1 cup of fresh chili peppers (100g): ~100-500 μM of capsaicin<br>
1 teaspoon of chili pepper extract (5g): ~100-500 μM of capsaicin<br>
1 tablespoon of chili pepper extract (15g): ~300-1500 μM of capsaicin<br>
<br>
Approximate μM concentrations of capsaicin in various foods that contain capsaicin:<br>
Jalapeño peppers: 1 pepper (20g): ~20-100 μM of capsaicin 2–8 mg/100g of fresh Jalapeño <br>
Serrano peppers: 1 pepper (10g): ~10-50 μM of capsaicin 5–15 mg/100g<br>
Cayenne peppers: 1 pepper (10g): ~50-200 μM of capsaicin<br>
Habanero peppers: 1 pepper (20g): ~100-500 μM of capsaicin 15–30 mg/100g<br>
Ghost peppers: 1 pepper (20g): ~200-1000 μM of capsaicin<br>
Hot sauce: 1 teaspoon (5g): ~10-50 μM of capsaicin<br>
Chili flakes: 1 teaspoon (5g): ~10-50 μM of capsaicin<br>
Spicy sauces and marinades: 1 tablespoon (15g): ~10-50 μM of capsaicin<br>
<br>
Cayenne Pepper Powder – Approximate capsaicin content: roughly 5–20 mg/g (15-30g human for 100uM?) <br>
<br>
-IC50 in Cancer Cell Lines: Approximately 50–300 µM (consume 150mg of capsaican not possible?)<br>
-IC50 in Normal Cell Lines: Generally higher—often 2–3 times greater <br>
<br>
Pathways:<br>
-disrupting mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspases<br>
-Activation of TRPV1: resulting in increased intracellular calcium levels<br>
-capsaicin can lead to increased production of ROS within cancer cells<br>
-Inhibition of NF-κB<br>
-Inhibit PI3K/AKT/mTOR signaling<br>
-STAT3 Inhibition<br>
-Cell Cycle Arrest<br>
-reduce the expression of vascular endothelial growth factor (VEGF)<br>
-COX-2<br>
-capsaicin is a natural ADAM10 activator and shows potential to attenuate amyloid pathology and protect against AD<br>

<br>


<table border="1" cellspacing="0" cellpadding="4">
<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>Oxidative stress / redox disruption</td>
<td>↑ ROS</td>
<td>Upstream cytotoxic trigger</td>
<td>Capsaicin increases intracellular ROS; ROS is positioned upstream of mitochondrial dysfunction and apoptosis in colon cancer cells</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6275774/">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓ ΔΨm</td>
<td>Mitochondrial dysfunction</td>
<td>Capsaicin disrupts mitochondrial transmembrane potential (ΔΨm) in human colon cancer cell lines</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6275774/">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>Intrinsic apoptosis (caspase-3 activation)</td>
<td>↑ caspase-3 / ↑ apoptosis</td>
<td>Execution-phase cell death</td>
<td>Capsaicin induces caspase-3 activation and apoptosis downstream of ROS and mitochondrial disruption</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6275774/">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>JAK/STAT3 signaling</td>
<td>↓ STAT3 activation</td>
<td>Reduced survival signaling</td>
<td>Capsaicin blocks constitutive and IL-6–inducible STAT3 activation (shown in multiple myeloma and other models)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/17505005/">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>AMPK → NF-κB axis (motility/invasion)</td>
<td>↑ AMPK / ↓ NF-κB</td>
<td>Anti-migration / anti-invasion</td>
<td>Esophageal squamous carcinoma study: capsaicin inhibits migration and invasion via AMPK activation and NF-κB suppression</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6682549/">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>NF-κB signaling (in vivo relevance)</td>
<td>↓ NF-κB pathway activity</td>
<td>Reduced pro-survival transcription</td>
<td>Breast cancer study links capsaicin anti-proliferation/pro-apoptosis to downregulation of an NF-κB–related axis (FBI-1 mediated)</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7811378/">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>TRPV6-dependent Ca2+ signaling (TRPV family)</td>
<td>↑ TRPV6 requirement / ↑ Ca2+-linked death signaling</td>
<td>Channel-dependent apoptosis (context-dependent)</td>
<td>Small-cell lung cancer study: capsaicin-induced apoptosis required TRPV6 (and was reported independent of TRPV1)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24878626/">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>Autophagy program (ROS–STAT3 coupling)</td>
<td>↑ autophagy (and can be targetable)</td>
<td>Stress response interacting with death</td>
<td>HepG2 study: capsaicin involves ROS/STAT3-dependent autophagy; inhibiting that autophagy enhanced capsaicin anticancer effects</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/27043357/">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>Cell-cycle regulation</td>
<td>↑ G0/G1 arrest (context-dependent)</td>
<td>Proliferation blockade</td>
<td>Bladder cancer study reports capsaicin-induced cell-cycle arrest (with associated cell-cycle protein changes)</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6272872/">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>Migration / invasion phenotype</td>
<td>↓ migration &amp; invasion</td>
<td>Anti-metastatic behavior (at cytotoxic dosing)</td>
<td>Oral cancer in vitro study reports capsaicin inhibits migration alongside pro-apoptotic effects</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11492975/">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>Context risk flag: low-dose pro-metastatic signaling</td>
<td>↑ ROS with ↑ Akt/mTOR and ↑ STAT3 (reported at low concentration)</td>
<td>Potential pro-metastatic phenotype (dose-dependent)</td>
<td>A paper reports low-concentration capsaicin promoted colorectal cancer metastasis via ROS and modulation of Akt/mTOR and STAT3 pathways (important dose-context caution)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/23581408/">(ref)</a></td>
</tr>

</table>

Pathway results for Effect on Cancer / Diseased Cells

Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↓, 2,   compI↓, 1,   ENOX2↓, 2,   ENOX2↑, 1,   GPx↓, 2,   GSH↓, 1,   GSH/GSSG↓, 1,   ROS↑, 13,   SOD↓, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   compIII↓, 1,   mitResp↓, 1,   MMP∅, 1,   MMP↓, 6,   MMP↑, 2,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   p‑AMPK↑, 1,   AMPK↑, 2,   ECAR↓, 1,   FBI-1↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 2,   lactateProd↓, 1,   NADPH↑, 1,   PDK1↓, 1,   SIRT1↑, 1,   SIRT1↓, 3,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 4,   Apoptosis↑, 9,   Bak↑, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Bcl-2↑, 1,   Bcl-xL↓, 2,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 5,   Casp3?, 1,   cl‑Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 3,   Fap1↓, 1,   iNOS↓, 1,   JNK↑, 3,   Proteasome↓, 1,   survivin↓, 2,   TRPV1↑, 5,   TRPV1?, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   other↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,   HSP70/HSPA5↓, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   LC3II↑, 2,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   ac‑P53↑, 1,   P53↑, 3,   cl‑PARP↑, 4,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 3,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   EMT↑, 1,   ERK↓, 1,   FOXO3↑, 2,   mTOR↑, 1,   mTOR↓, 2,   PI3K↓, 2,   PTEN↑, 1,   Src↓, 1,   p‑STAT3↑, 1,   STAT3↓, 1,   STAT3↑, 2,   TumCG↓, 3,  

Migration ⓘ

ATPase↓, 1,   Ca+2↑, 4,   i-Ca+2?, 1,   COL1A1↓, 1,   COL3A1↓, 1,   E-cadherin↑, 1,   p‑FAK↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP2↑, 1,   MMP9↓, 3,   MMP9↑, 1,   N-cadherin↓, 1,   p‑pax↓, 1,   PKA↓, 1,   TIMP1↓, 1,   TumCI↓, 1,   TumCI↑, 1,   TumCMig↓, 5,   TumCMig↑, 2,   TumCP↓, 6,   TumCP↑, 1,   TumMeta↓, 1,   TumMeta↑, 1,   α-SMA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 1,   EPR↑, 1,   Hif1a↓, 2,   VEGF↓, 3,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   p‑IκB↑, 1,   NF-kB↓, 4,   PD-1↓, 1,   PD-L1↓, 1,   PSA↓, 2,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 2,   ChemoSen↑, 3,   Dose∅, 3,   Dose?, 1,   Dose↝, 1,   eff↑, 12,   eff∅, 1,   eff↓, 3,   Half-Life∅, 1,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

AR↓, 2,   EGFR↓, 1,   GutMicro↓, 1,   Ki-67↓, 1,   PD-L1↓, 1,   PSA↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiCan↓, 2,   AntiTum↑, 3,   chemoPv↑, 3,   RenoP↑, 1,   Risk↑, 1,   TumVol↓, 1,  
Total Targets: 149

Pathway results for Effect on Normal Cells

Redox & Oxidative Stress ⓘ

GSS↑, 1,   HO-1↑, 1,   Keap1↓, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS∅, 2,   ROS↓, 3,   Trx↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   mitResp↑, 1,   MMP∅, 1,   mtDam↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ECAR↓, 1,   FAO↑, 1,   FASN↓, 1,   LDHA↓, 2,   PGM1?, 1,   PKM2↓, 4,   PPARα↑, 2,   SREBP2↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Casp3∅, 1,   Cyt‑c∅, 1,   TRPV1↑, 1,  

Transcription & Epigenetics ⓘ

other↓, 6,  

Migration ⓘ

APP↓, 1,   MMP-10↝, 1,   PKA↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IFN-γ↓, 1,   IL6↓, 1,   Inflam↓, 6,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   ADAM10↑, 1,   BDNF↑, 1,   p‑tau↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 2,   memory↑, 1,   neuroP↑, 2,   Risk↓, 2,   toxicity∅, 1,   toxicity↓, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 2,  
Total Targets: 50

Research papers

Year Title Authors PMID Link Flag
2013Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicinLaurent Schwartz 22797854https://pubmed.ncbi.nlm.nih.gov/22797854/0
2025Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interactionXiaoning Gao—https://elifesciences.org/reviewed-preprints/976320
2025The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer’s diseaseXudong Sha—https://www.nature.com/articles/s41419-024-07328-8.pdf0
2024Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and DiseaseMichela MusolinoPMC10815060https://pmc.ncbi.nlm.nih.gov/articles/PMC10815060/0
2024Capsaicin Promotes Apoptosis and Inhibits Cell Migration via the Tumor Necrosis Factor-Alpha (TNFα) and Nuclear Factor Kappa B (NFκB) Signaling Pathway in Oral Cancer CellsNiranjana ArivalaganPMC11492975https://pmc.ncbi.nlm.nih.gov/articles/PMC11492975/0
2023Capsaicinoids and Their Effects on Cancer: The “Double-Edged Sword” Postulate from the Molecular ScaleFrancisco Luján-MéndezPMC10650825https://pmc.ncbi.nlm.nih.gov/articles/PMC10650825/0
2023Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical EvidenceZohra Nausheen NizamiPMC10295724https://pmc.ncbi.nlm.nih.gov/articles/PMC10295724/0
2023Capsaicin shapes gut microbiota and pre-metastatic niche to facilitate cancer metastasis to liverPeng Cheng36608780https://pubmed.ncbi.nlm.nih.gov/36608780/0
2023Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin)Chaitanya A PatwardhanPMC10447550https://pmc.ncbi.nlm.nih.gov/articles/PMC10447550/0
2023Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometryZifang Peng—https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1227517/full0
2023Anti-cancer Activity of Sustained Release Capsaicin FormulationsJustin C MerrittPMC9510151https://pmc.ncbi.nlm.nih.gov/articles/PMC9510151/0
2022Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cellsTae-Hee Han—https://www.sciencedirect.com/science/article/pii/S07533322210128650
2022Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human CancerTomi Lois AdetunjiPMC9326111https://pmc.ncbi.nlm.nih.gov/articles/PMC9326111/0
2022Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsisQian Zhang35858615https://www.sciencedirect.com/science/article/pii/S24519456220024340
2021Capsaicin Inhibits Proliferation and Induces Apoptosis in Breast Cancer by Down-Regulating FBI-1-Mediated NF-κB PathwayMaojian ChenPMC7811378https://pmc.ncbi.nlm.nih.gov/articles/PMC7811378/0
2020Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 miceJun WangPMC7359297https://pmc.ncbi.nlm.nih.gov/articles/PMC7359297/0
2020Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 miceJun Wang—https://www.nature.com/articles/s41398-020-00918-y.pdf0
2019Capsaicin induces cytotoxicity in human osteosarcoma MG63 cells through TRPV1-dependent and -independent pathwaysZhengqi BaoPMC6592244https://pmc.ncbi.nlm.nih.gov/articles/PMC6592244/0
2019Capsaicin: Effects on the Pathogenesis of Hepatocellular CarcinomaCristian ScheauPMC6651067https://pmc.ncbi.nlm.nih.gov/articles/PMC6651067/0
2019Capsaicin inhibits the migration and invasion via the AMPK/NF-κB signaling pathway in esophagus sequamous cell carcinoma by decreasing matrix metalloproteinase-9 expressionYong GuoPMC6682549https://pmc.ncbi.nlm.nih.gov/articles/PMC6682549/0
2018Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to DoxorubicinHanmei LiPMC6017796https://pmc.ncbi.nlm.nih.gov/articles/PMC6017796/0
2018Capsaicin inhibits glycolysis in esophageal squamous cell carcinoma by regulating hexokinase‑2 expressionXinli Mao—https://www.spandidos-publications.com/10.3892/mmr.2018.85740
2016Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)Ming-Hung Lin—https://www.mdpi.com/1420-3049/21/7/8490
2016Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated PathwaysKaiyu QianPMC6272872https://pmc.ncbi.nlm.nih.gov/articles/PMC6272872/0
2016Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cellsXun Chen27043357https://pubmed.ncbi.nlm.nih.gov/27043357/0
2015Capsaicin Induces Apoptosis in Human Small Cell Lung Cancer via the TRPV6 Receptor and the Calpain PathwayJamie K LauPMC4072851https://pmc.ncbi.nlm.nih.gov/articles/PMC4072851/0
2014Capsaicin modulates proliferation, migration, and activation of hepatic stellate cellsShanna Bitencourt23955514https://pubmed.ncbi.nlm.nih.gov/23955514/0
2013Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathwaysJ Yang23581408https://pubmed.ncbi.nlm.nih.gov/23581408/0
2012Capsaicin-mediated tNOX (ENOX2) up-regulation enhances cell proliferation and migration in vitro and in vivoNei-Chi Liu22353011https://pubmed.ncbi.nlm.nih.gov/22353011/1
2011Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer CellsKartick C PramanikPMC3102063https://pmc.ncbi.nlm.nih.gov/articles/PMC3102063/0
2009Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell linesKyung Min YangPMC6275774https://pmc.ncbi.nlm.nih.gov/articles/PMC6275774/0
2007Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activationManisha Bhutani17505005https://pubmed.ncbi.nlm.nih.gov/17505005/0
2006Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cellsAkio Mori16540674https://pubmed.ncbi.nlm.nih.gov/16540674/0
2004Capsaicin inhibits in vitro and in vivo angiogenesisJeong-Ki Min14744780https://pubmed.ncbi.nlm.nih.gov/14744780/0
2000Capsaicin effects on brain-derived neurotrophic factor in rat dorsal root ganglia and spinal cordSun-Ok Ha—https://www.sciencedirect.com/science/article/abs/pii/S0169328X000014430
2022Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessmentPriyashi Rao—https://journals.plos.org/plosone/article?id=10.1371/journal.pone.02690360
2014Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of subjects ages 40-84Claudia HanauPMC3901999https://pmc.ncbi.nlm.nih.gov/articles/PMC3901999/0
2011Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiolLian-Ying Wu—https://www.sciencedirect.com/science/article/abs/pii/S03044165110009360
2019The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen ReceptorCatalina Carrasco-PozoPMC6861939https://pmc.ncbi.nlm.nih.gov/articles/PMC6861939/0