Database Query Results : Spermidine, ,

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.
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⟱
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↑,
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↓,
4893- Sper,  immuno,    Chemoproteomic Identification of Spermidine-Binding Proteins and Antitumor-Immunity Activators
- in-vitro, Var, NA
*mt-FAO↑, eff↑,
4894- Sper,    Application of Spermidine in Cancer Research Models: Notes and Protocols
- Review, Var, NA
TumAuto↑, AntiTum↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑,
4895- Sper,    Spermidine as a target for cancer therapy
- Review, Var, NA - Review, AD, NA
TumAuto↑, Apoptosis↑, OS↑, CRM↑, TumCG⇅, cardioP↑, cognitive↑, *Dose⇅,
4896- Sper,  immuno,    Spermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer
- vitro+vivo, BC, NA
eff↑, AntiTum↑,
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↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

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 ⓘ

CRM↑, 1,  

Cell Death ⓘ

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

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3B-II↑, 1,   TumAuto↑, 4,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,   TumCG⇅, 1,  

Migration ⓘ

TumCP↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 3,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 3,   cardioP↑, 1,   cognitive↑, 1,   OS↑, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

mitResp↑, 1,  

Core Metabolism/Glycolysis ⓘ

mt-FAO↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose⇅, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cognitive↑, 1,   neuroP↑, 1,  
Total Targets: 10

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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