Spermidine Cancer Research Results

Sper, Spermidine: Click to Expand ⟱
Features:
Spermidine : Polyamine (natural small molecule)
Sources: Found in foods like wheat germ, soybeans, mushrooms, aged cheese, and fermented foods. Typical dietary intake is ~5–20 mg/day.Top food sources = wheat germ > soybeans > aged cheddar > mushrooms > rice bran/legumes.

Ripening / fermentation: especially in aged or fermented foods like cheese, where spermidine and other polyamines can rise during ripening because microbial activity and protein breakdown contribute to amine formation. That is one reason aged cheeses can rank unusually high.
Cooking: boiling and grilling significantly reduced polyamine content in many foods, whereas microwave and sous-vide tended to preserve more.

Primary Actions: Autophagy induction, mild ROS modulation, epigenetic regulation, and modulation of polyamine metabolism.
Pathway	                Effect of Spermidine
Autophagy (ATG genes)	↑ Induction, Beclin-1 activation
mTORC1 signaling	↓ Inhibition, promotes catabolic metabolism
p53/p21	                Modulation via epigenetic changes
Polyamine metabolism	Supports or stresses proliferating cells
ROS / redox balance	Mild modulation; sensitizes cancer cells to ROS stress
Context-dependent risk: High spermidine levels might support tumor growth in polyamine-addicted cancers; dose, timing, and tumor type matter.

Chemo interaction: Generally compatible; not expected to block ROS-dependent therapy at oral doses.

Spermidine, a biogenic polyamine that declines along with aging, shows promise in restoring antitumor immunity by enhancing mitochondrial fatty acid oxidation (FAO)

Spermidine — Cancer vs Normal Cell Effects
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Autophagy induction (ATG program) ↑ autophagy → metabolic stress, growth restraint ↑ autophagy → cytoprotection, homeostasis Driver Autophagy-first mechanism Spermidine robustly induces autophagy independent of mTOR inhibition; cancer cells are more vulnerable to enforced catabolism
2 Epigenetic regulation (histone acetylation) ↓ histone acetylation (via HAT inhibition) ↓ acetylation (adaptive) Driver Chromatin-mediated transcriptional reprogramming Spermidine inhibits histone acetyltransferase activity, promoting a pro-autophagic, anti-proliferative transcriptional state
3 Polyamine metabolism / homeostasis Disrupted polyamine balance Homeostatic buffering Driver Metabolic vulnerability Cancer cells are highly dependent on polyamine flux; spermidine perturbs this balance
4 AMPK / mTOR nutrient-sensing axis ↑ AMPK; ↓ mTOR signaling ↑ AMPK (adaptive) Secondary Catabolic pressure Energy-sensing pathways reinforce autophagy and growth suppression
5 Mitochondrial function / bioenergetics ↓ metabolic flexibility ↑ mitochondrial efficiency Secondary Energy stress vs optimization Autophagy-driven mitochondrial turnover stresses tumor bioenergetics while benefiting normal cells
6 Reactive oxygen species (ROS) ↑ ROS (secondary, stress-linked) ↓ ROS Secondary Metabolism-linked redox shift ROS changes arise indirectly from autophagy and mitochondrial remodeling, not direct redox chemistry
7 NRF2 antioxidant response ↑ NRF2 (adaptive, secondary) ↑ NRF2 (protective) Adaptive Redox homeostasis reinforcement NRF2 activation reflects compensatory antioxidant signaling rather than a cytotoxic mechanism
8 Cell cycle / proliferation ↓ proliferation / ↑ arrest ↔ spared Phenotypic Cytostatic growth limitation Growth inhibition reflects sustained autophagy and epigenetic effects
9 Apoptosis sensitivity ↑ sensitivity to apoptosis (context-dependent) ↓ apoptosis Phenotypic Threshold-dependent cell death Apoptosis occurs when catabolic stress exceeds adaptive capacity


Scientific Papers found: Click to Expand⟱
5791- CRMs,  HCA,  NAD,  Sper,  RES  Caloric Restriction Mimetics in Nutrition and Clinical Trials
- Review, Nor, NA
*Dose↝, *Glycolysis↓,
5780- CRMs,  HCAs,  RES,  Sper,  ASA  Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
- Review, Var, NA
*OS↑, *AntiAge↑, *cardioP↑, *neuroP↑, AntiCan↑, *TNF-α↓, *Weight↓, *BP↓, *Inflam↓, *Insulin↓, *ROS↓, *AMPK↑, *mTOR↓, *SIRT1↑, CRM↑,
1627- HCA,  CRMs,  Sper,    Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance
- Review, Var, NA
ChemoSen↑, eff↑, ACLY↓, LC3‑Ⅱ/LC3‑Ⅰ↑, TumAuto↑, other↓,
5782- Sper,    Cardioprotection and lifespan extension by the natural polyamine spermidine
- in-vivo, Nor, NA
cardioP↑, eff↓, AntiAge↑, BioAv↑, CRM↝,
5806- Sper,    Spermidine – an old molecule with a new age-defying immune function
GutMicro↝, GutMicro↝,
5805- Sper,    The Effect of Spermidine Supplementation on Cognitive Function in Adults: A Mini-Review
- Review, AD, NA
*cognitive↝, *Dose↝,
5802- Sper,    Spermidine reduces cancer-related mortality in humans
- Review, Var, NA
EP300↓, Risk↓,
5799- Sper,    The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial
- Trial, AD, NA
*cognitive↑, memory↑, *Dose↑, *Dose↑, *Dose↝, *Dose↝, BioAv↓, eff↑,
5794- Sper,    Spermidine induces autophagy by inhibiting the acetyltransferase EP300
- in-vitro, Nor, U2OS
*EP300↓, *mTORC1↓, *CRM↑, *HATs↓, *p62↓, *AntiAge↑, AntiCan↑,
5790- Sper,    The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial
- Trial, Nor, NA
*memory↑,
5789- Sper,    Long-term oral polyamine intake increases blood polyamine concentrations
- Human, Nor, NA
*Dose↝, *BioAv↑,
4897- Sper,    Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms
- Review, Var, NA
Inflam↓, TumAuto↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑, Bcl-2↓,
4896- Sper,  immuno,    Spermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer
- vitro+vivo, BC, NA
eff↑, AntiTum↑,
4895- Sper,    Spermidine as a target for cancer therapy
- Review, Var, NA - Review, AD, NA
TumAuto↑, Apoptosis↑, OS↑, CRM↑, TumCG⇅, cardioP↑, cognitive↑, *Dose⇅,
4894- Sper,    Application of Spermidine in Cancer Research Models: Notes and Protocols
- Review, Var, NA
TumAuto↑, AntiTum↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑,
4893- Sper,  immuno,    Chemoproteomic Identification of Spermidine-Binding Proteins and Antitumor-Immunity Activators
- in-vitro, Var, NA
*mt-FAO↑, eff↑,
4892- Sper,  erastin,    Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer
- in-vitro, Pca, PC3 - in-vivo, Pca, NA
Ferroptosis↑, lipid-P↑, Iron↑, eff↑, HO-1↑, NRF2↑, ROS↑, AntiTum↑, eff↓,
4891- Sper,    Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms
- Review, Var, NA - Review, AD, NA
TumCCA↑, TumCP↓, TumCG↓, *Inflam↓, *antiOx↑, *neuroP↑, *cognitive↑, *Aβ↓, *mitResp↑, AntiCan↑, TumCD↑, TumAuto↑, *AntiAge↑, LC3B-II↑, ATG5↑, Beclin-1↑, mt-ROS↑, H2O2↑, Apoptosis↑, *ROS↑, ChemoSen↑, MMP↓, Cyt‑c↑,

Showing Research Papers: 1 to 18 of 18

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 18

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   H2O2↑, 1,   HO-1↑, 1,   Iron↑, 1,   lipid-P↑, 1,   NRF2↑, 1,   ROS↑, 3,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   CRM↑, 2,   CRM↝, 1,  

Cell Death ⓘ

Apoptosis↑, 4,   Bcl-2↓, 1,   Cyt‑c↑, 3,   Ferroptosis↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B-II↑, 1,   TumAuto↑, 5,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EP300↓, 1,   TumCG↓, 1,   TumCG⇅, 1,  

Migration ⓘ

TumCP↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 2,   eff↓, 2,   eff↑, 5,  

Clinical Biomarkers ⓘ

GutMicro↝, 2,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiCan↑, 3,   AntiTum↑, 3,   cardioP↑, 2,   cognitive↑, 1,   memory↑, 1,   OS↑, 1,   Risk↓, 1,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

Insulin↓, 1,   mitResp↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   CRM↑, 1,   mt-FAO↑, 1,   Glycolysis↓, 1,   SIRT1↑, 1,  

Transcription & Epigenetics ⓘ

HATs↓, 1,  

Autophagy & Lysosomes ⓘ

p62↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EP300↓, 1,   mTOR↓, 1,   mTORC1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   Dose↑, 2,   Dose⇅, 1,   Dose↝, 5,  

Clinical Biomarkers ⓘ

BP↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 3,   cardioP↑, 1,   cognitive↑, 2,   cognitive↝, 1,   memory↑, 1,   neuroP↑, 2,   OS↑, 1,   Weight↓, 1,  
Total Targets: 31

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#:386  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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