Capsaicin / TumCCA Cancer Research Results

CAP, Capsaicin: Click to Expand ⟱

Features:

Capsaicin is a chemical compound that gives chili peppers their spicy flavor and heat.

Biological activity, capsaicin has been reported to exhibit a range of effects, including:
Pain relief: 10-50 μM
Anti-inflammatory activity: 20-50 μM
Antioxidant activity: 10-100 μM
Anti-cancer activity: 50-100 μM
Cardiovascular health: 20-50 μM

Approximate μM concentrations of capsaicin, the active compound in chili peppers, that can be achieved with different amounts of chili peppers:
1 teaspoon of dried chili pepper flakes (5g):~10-50 μM of capsaicin
1 tablespoon of dried chili pepper flakes (15g): ~30-150 μM of capsaicin
1 cup of fresh chili peppers (100g): ~100-500 μM of capsaicin
1 teaspoon of chili pepper extract (5g): ~100-500 μM of capsaicin
1 tablespoon of chili pepper extract (15g): ~300-1500 μM of capsaicin

Approximate μM concentrations of capsaicin in various foods that contain capsaicin:
Jalapeño peppers: 1 pepper (20g): ~20-100 μM of capsaicin 2–8 mg/100g of fresh Jalapeño
Serrano peppers: 1 pepper (10g): ~10-50 μM of capsaicin 5–15 mg/100g
Cayenne peppers: 1 pepper (10g): ~50-200 μM of capsaicin
Habanero peppers: 1 pepper (20g): ~100-500 μM of capsaicin 15–30 mg/100g
Ghost peppers: 1 pepper (20g): ~200-1000 μM of capsaicin
Hot sauce: 1 teaspoon (5g): ~10-50 μM of capsaicin
Chili flakes: 1 teaspoon (5g): ~10-50 μM of capsaicin
Spicy sauces and marinades: 1 tablespoon (15g): ~10-50 μM of capsaicin

Cayenne Pepper Powder – Approximate capsaicin content: roughly 5–20 mg/g (15-30g human for 100uM?)

-IC50 in Cancer Cell Lines: Approximately 50–300 µM (consume 150mg of capsaican not possible?)
-IC50 in Normal Cell Lines: Generally higher—often 2–3 times greater

Pathways:
-disrupting mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspases
-Activation of TRPV1: resulting in increased intracellular calcium levels
-capsaicin can lead to increased production of ROS within cancer cells
-Inhibition of NF-κB
-Inhibit PI3K/AKT/mTOR signaling
-STAT3 Inhibition
-Cell Cycle Arrest
-reduce the expression of vascular endothelial growth factor (VEGF)
-COX-2
-capsaicin is a natural ADAM10 activator and shows potential to attenuate amyloid pathology and protect against AD

Capsaicin — capsaicin is a pungent vanilloid alkaloid phytochemical from Capsicum peppers and the principal TRPV1 agonist responsible for chili heat. It is best classified as a natural product / small-molecule vanilloid with approved topical analgesic use but no established anticancer indication. Standard abbreviations include CAP and CAPS. In cancer literature it is a pleiotropic stressor whose dominant preclinical effects usually converge on Ca2+ influx, mitochondrial dysfunction, ROS generation, suppression of pro-survival signaling, and apoptosis, but its biology is context- and concentration-dependent, with occasional low-dose pro-migratory / pro-metastatic signaling reported.

Primary mechanisms (ranked):

TRPV-linked cation influx with intracellular Ca2+ dysregulation, variably via TRPV1 or other TRPV-family context such as TRPV6
Mitochondrial injury with loss of membrane potential, cytochrome c release, and intrinsic apoptotic execution
Mitochondrial and cellular ROS increase with redox stress exceeding tumor buffering capacity
Suppression of STAT3 and related survival transcription programs in multiple models
Suppression of NF-κB-centered inflammatory / survival signaling, with downstream anti-migratory and radiosensitizing implications in some settings
PI3K/Akt/mTOR attenuation and cell-cycle restraint in responsive models
Contextual induction of autophagy as a stress-adaptation program that may either accompany death or partially buffer it
Anti-migratory / anti-invasive effects in many models, but with an important low-concentration exception in some colorectal systems

Bioavailability / PK relevance: Capsaicin is lipophilic, rapidly absorbed, and rapidly metabolized, with substantial first-pass limitation after oral exposure. Human oral PK from a capsicum preparation containing 26.6 mg capsaicin produced a Cmax of about 2.47 ng/mL at ~47 minutes, while the FDA-approved 8% topical system produced transient systemic exposure usually below 5 ng/mL, with a highest detected plasma level of 4.6 ng/mL. Delivery is therefore a major translation constraint for anticancer use, and formulation-based approaches are often invoked to overcome short half-life, irritancy, and exposure limits.

In-vitro vs systemic exposure relevance: This is a major limitation. Many anticancer cell studies use roughly 10–300 µM, whereas reported human plasma exposures from oral or approved topical use are in the low ng/mL range, approximately ~0.008–0.015 µM, i.e., orders of magnitude lower than many cytotoxic in-vitro concentrations. Accordingly, direct systemic tumoricidal translation from standard dietary or approved topical exposure is weak unless local delivery, sustained-release systems, or substantially altered formulations are used.

Clinical evidence status: Anticancer evidence is predominantly preclinical, with in-vitro and some in-vivo support across several tumor types. There is no regulatory approval for cancer treatment. Human oncology use is currently much more credible as supportive care for neuropathic pain, especially chemotherapy-induced peripheral neuropathy, where topical high-concentration capsaicin patches are being studied and used off-label / investigationally, rather than as a direct antitumor therapy.

Mechanistic Table

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	TRPV-linked Ca2+ influx	Ca2+ ↑; death signaling ↑	Sensory excitation ↑; irritancy ↑	P/R	Upstream trigger	Usually framed through TRPV1, but some tumor models show dependence on other TRPV-family context such as TRPV6; this is mechanistically central but not uniform across cancers.
2	Mitochondrial membrane potential	MMP ↓; cytochrome c release ↑	↔ / stress if exposed	R	Intrinsic apoptosis initiation	Mitochondrial dysfunction is one of the most reproducible downstream events and often links Ca2+ overload with apoptosis.
3	Mitochondrial ROS increase	ROS ↑; redox buffering overwhelmed	↔ / antioxidant response may compensate	P/R	Stress amplification	Frequently sits upstream of mitochondrial collapse, DNA damage signaling, and apoptosis; cancer selectivity is often attributed to weaker redox reserve.
4	Intrinsic apoptosis machinery	BAX/Bak ↑; Bcl-2/Bcl-xL ↓; caspase-3/9 ↑	↔ / lower sensitivity in some comparisons	R/G	Execution-phase cell death	Common endpoint across responsive models; often follows ROS and mitochondrial injury rather than acting as the primary initiating lesion.
5	STAT3 survival signaling	STAT3 ↓	↔	R/G	Reduced survival and proliferation	Well supported in multiple myeloma and other models, but not universal; note that a HepG2 context reported ROS-associated STAT3 activation coupled to autophagy.
6	NF-κB inflammatory survival axis	NF-κB ↓	Inflammatory tone ↓	R/G	Anti-survival; anti-migratory	Important for invasion restraint and likely part of observed radiosensitization in some models.
7	PI3K Akt mTOR axis	PI3K/Akt/mTOR ↓	↔	R/G	Growth suppression	Seen in several responsive systems, but this axis is also part of the cautionary low-dose pro-metastatic literature in colorectal cancer.
8	Cell-cycle control	G0/G1 or G1/S arrest ↑	↔	G	Proliferation blockade	Usually secondary to upstream stress and survival-pathway suppression rather than the earliest event.
9	Autophagy stress program	Autophagy ↑ (context-dependent)	↔	G	Adaptive buffering or co-lethal stress	In HepG2, autophagy appeared partially protective because inhibiting it enhanced capsaicin-induced apoptosis.
10	Migration invasion EMT phenotype	Migration ↓; invasion ↓; EMT ↓ (context-dependent)	↔	G	Anti-metastatic phenotype	Frequently reported at active doses, often linked to AMPK activation and NF-κB suppression.
11	Low-dose paradox flag	ROS ↑ with Akt/mTOR ↑ and STAT3 ↑ (model-dependent)	↔	G	Potential pro-metastatic signaling	Important caution: low-concentration capsaicin has been reported to enhance metastatic behavior in colorectal cancer models.
12	Radiosensitization or Chemosensitization	Sensitivity ↑ (context-dependent)	Unknown	G	Adjunct potential	Preclinical support exists, especially via NF-κB and stress-pathway modulation, but this remains non-clinically established for direct cancer treatment.
13	Clinical Translation Constraint	Required tumoricidal exposure often not reached systemically	Irritation and tolerability limit escalation	G	Translation bottleneck	Typical antitumor in-vitro concentrations greatly exceed known plasma exposure from standard oral intake or approved topical use; formulation, local delivery, and tumor heterogeneity are major constraints.

P: 0–30 min

R: 30 min–3 hr

G: >3 hr

TumCCA, Tumor cell cycle arrest: Click to Expand ⟱

Source:

Type:

Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.

Scientific Papers found: Click to Expand⟱

5842-

CAP,

Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses

Review,

Nor,

Review,

Diabetic,

*Pain↓, *TRPV1↑, AMPK↑, ROS↑, TumCP↑, Apoptosis↑, TumCCA↑, Casp3↑, BAX↑, Bak↑, cl‑PARP↑, Bcl-2↓, RNS↑, *glucose↓, *Insulin↑, *BP↓, *AntiAg↑, ER Stress↑, Hif1a↓, chemoPv↑,

5838-

CAP,

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway

in-vitro,

NPC,

TumCG↓, TumCCA↑, TumAuto↑, Casp3↑, Ca+2↑, ROS↑, MMP↓, LC3‑Ⅱ/LC3‑Ⅰ↑, ATG5↑, p62↓, Fap1↓, PI3K↓, DNAdam↑,

5833-

CAP,

Capsaicin: From Plants to a Cancer-Suppressing Agent

Review,

Var,

chemoPv↑, TumCCA↑, Apoptosis↑, ROS↑, MMP↓, Ca+2↑, JNK↑, Casp3↑, NADH↓, CDK2↓, CDK4↓, CDK6↓, P53↑,

5832-

CAP,

Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells

in-vitro,

Oral,

50, 100, 150, 200 and 250 μM

TumCP↓, tumCV↓, TumCCA↑, Apoptosis↑, MMP↓, Casp9↑, Casp3↑, PARP↑, Inflam↓, Pain↓,

5828-

CAP,

Capsaicin: a novel radio-sensitizing agent for prostate cancer

vitro+vivo,

Pca,

LNCaP

effects of RT (1-8 Gy) and/or capsaicin (1-10 µM) on colony formation rates in human PCa cells (in mice)

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

RadioS↑, NF-kB↓, TumCCA↑, TumCG↓, TumCP↓, DNAdam↑, γH2AX↑, Ki-67↓,

5861-

CAP,

Anticancer Properties of Capsaicin Against Human Cancer

Review,

Var,

*antiOx↑, *Inflam↓, *Obesity↓, chemoPv↑, Apoptosis↑, selectivity↑, TRPV1↑, Ca+2↑, mtDam↑, Cyt‑c↑, P53↑, SIRT1↓, TumCCA↑, P21↑, CDK4↓, CDK6↓, cycE/CCNE↓, angioG↓, TumMeta↓,

5849-

CAP,

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Review,

Var,

TRPV1↑, Ca+2↑, TumCD↑, TumCCA↑, Apoptosis↑, P53↑, Fas↑, PI3K↑, AR↑, STAT3↓, ROS↑, MMP↓, ATP↓, CHOP↑, TumCMig↓, Twist↓, Snail↓, MMP2↓, MMP9↓, E-cadherin↑,

5847-

CAP,

An updated review on molecular mechanisms underlying the anticancer effects of capsaicin

in-vitro,

Liver,

HepG2

HO-1↑, ROS↑, NRF2↑, *lipid-P↓, *SOD↑, *Catalase↑, *GPx↑, *GSR↑, *PGE2↓, *COX2↓, *iNOS↓, TumCP↓, TumCCA↑, cycE/CCNE↓, CDK4↓, MMP↓, P53↑, P21↑, BAX↑, SIRT1↑, angioG↓, P-gp↓, ChemoSen↑,

5845-

CAP,

Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines

in-vivo,

RCC,

A498

in-vitro,

RCC,

T24/HTB-9

NA,

Bladder,

5637

TRPV1↑, TumCP↓, Casp↑, Apoptosis↑, SIRT1↓, MMP2↓, MMP9↓, TumCMig↓, TumCCA↑, ROS↑, DNAdam↑, PD-L1↑, eff↓,

1517-

CAP,

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)

in-vitro,

Bladder,

TSGH8301

in-vitro,

CRC,

T24/HTB-9

ENOX2↓, TumCCA↑, ERK↓, p‑FAK↓, p‑pax↓, TumCMig↓, EMT↓, SIRT1↓, Dose∅, ROS↑, MMP↓, Bcl-2↓, Bak↑, cl‑PARP↑, Casp3↑, SIRT1↓, ac‑P53↑, BIM↑, p‑RB1↓, cycD1/CCND1↓, Dose∅, β-catenin/ZEB1↓, N-cadherin↓, E-cadherin↑,

1264-

CAP,

Capsaicin modulates proliferation, migration, and activation of hepatic stellate cells

in-vitro,

HCC,

100 lM

TumCP↓, TumCMig↓, TumCCA↑, MMP∅, MMP2↓, MMP9↓, α-SMA↓, COL1A1↓, COL3A1↓, TIMP1↓,

1260-

CAP,

Capsaicin inhibits in vitro and in vivo angiogenesis

vitro+vivo,

NA,

VEGF↓, angioG↓, TumCCA↑, cycD1/CCND1↓, Akt↓,

5202-

CAP,

Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways

vitro+vivo,

Bladder,

5637

0, 50, 100, 150, 200 and 300 µM

and NOD/SCID mice.

in-vitro,

Bladder,

T24/HTB-9

antiOx↑, Inflam↓, AntiCan↓, TRPV1↑, TumCP↓, TumCCA↑, ROS↑, FOXO3↑, TumCMig↓,

5199-

CAP,

Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation

vitro+vivo,

AML,

 i.p., capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male athymic nu/nu mice.

STAT3↓, cycD1/CCND1↓, Bcl-2↓, Bcl-xL↓, survivin↓, VEGF↓, TumCCA↑, Apoptosis↑, Casp↑, eff↑,

2652-

CAP,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, AntiCan↑, ROS↑, TumCG↓, ROS↑, MMP↑, Apoptosis↑, TumCCA↑, JNK↑, SOD↓, Catalase↓, GPx↓, other↓, SIRT1↓, NADPH↑, FOXO3↑,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Catalase↑, 1, GPx↑, 1, GSR↑, 1, lipid-P↓, 1, SOD↑, 1,

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1,

Core Metabolism/Glycolysis ⓘ

glucose↓, 1,

Cell Death ⓘ

iNOS↓, 1, TRPV1↑, 1,

Migration ⓘ

AntiAg↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 1, PGE2↓, 1,

Clinical Biomarkers ⓘ

BP↓, 1,

Functional Outcomes ⓘ

Obesity↓, 1, Pain↓, 1,
Total Targets: 17

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest

15 Capsaicin

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:55  Target#:322  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Capsaicin / TumCCA Cancer Research Results

Mechanistic Table

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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