Alpha-Lipoic-Acid / NF-kB Cancer Research Results

ALA, Alpha-Lipoic-Acid: Click to Expand ⟱
Features: antioxidant, energy production in cell mitochondria
Alpha-Lipoic-Acid: also known as lipoic acid or thioctic acid (reduced form is dihydrolipoic acid).
"Universal antioxidant" because it is both water- and fat-soluble and can neutralize free radicals.
-Treatment sometimes as ALA/N (alpha-lipoic acid/low-dose naltresone)
-Also done in IV
-Decreases ROS production, but also has pro-oxidant role.
Normal adult can take 300 milligrams twice a day with food, but they should always take a B-complex vitamin with it. Because B complex vitamins, especially thiamine, and biotin, and riboflavin, are depleted during this metabolic process.
α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
-It seems a paradox that LA functions as both antioxidant and prooxidant. LA functions the pro-oxidant only in special cancer cells, such as A549 and PC9 cells which should show high-level NRF2 expression and high glycolytic level. Through inhibiting PDK1 to further prohibit NRF2; LA functions as anticancer prooxidant.

α-lipoic acid possesses excellent silver chelating properties.

ALA → ROS ↑ (cancer cells; high dose / stressed mitochondria)
ALA → ROS ↓ (normal cells; low–moderate dose)
same pattern seen with: Vitamin C, Menadione, Quercetin, EGCG, Resveratrol
- ALA acts as pro-Oxidant only in cancer cells:#278 - Pro-Oxidant Dose margin >100uM:#304

- Bioavailability: 80-90%, but conversion to EPA/DHA is 5-10% (and takes longer time).
- AI (Adequate Intake): 1.1-1.6g/day.
- human studies have shown that ALA levels decline significantly with age
- 1g of ALA might achieve 500uM in the blood.
- ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
- Pilot studies or observational interventions have used flaxseed supplementation (rich in ALA) in doses providing roughly 3–4 g of ALA daily.
- Flaxseed oil is even more concentrated in ALA – typical 50–60% ALA by weight.
- single walnut may contain 300mg of ALA
- chia oil contains 55-65% ALA.
- α-LA can also be obtained from the diet through the consumption of dark green leafy vegetables and meats
- ALA is more stable in chia seeds, (2grams of ALA per tablespoon)
- ALA degrades when exposed to heat, light, and air. (prone to oxidation)

-Note half-life 1-2 hrs.
BioAv 30-40% from walnuts, 60-80% from supplements. Co-ingestion with fat improves absorption. Both fat and water soluble
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓">NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- small indication of inhibiting Cancer Stem Cells : CSC↓, CD24↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Cancer-Relevant Pathways
Rank Pathway / Axis Cancer Cells Normal Cells Label Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & stress-dependent) ↓ ROS Conditional Driver Biphasic redox behavior ALA/DHLA redox cycling can push already stressed cancer mitochondria past tolerance while buffering ROS in normal cells
2 Glutathione (GSH) system ↓ functional buffering ↑ GSH regeneration Secondary Redox amplification vs protection In cancer cells, GSH consumption accompanies ROS escalation; in normal cells DHLA supports GSH recycling
3 Mitochondrial function (ΔΨm) ↓ ΔΨm (stress-induced) ↔ stabilized Secondary Mitochondrial selectivity Cancer cells with unstable ETC show depolarization; normal cells tolerate or benefit metabolically
4 NF-κB signaling ↓ survival signaling ↓ inflammatory tone Secondary Redox-sensitive transcription NF-κB suppression reduces cancer cell survival programs but is anti-inflammatory in normal tissue
5 Cell proliferation ↓ proliferation ↔ spared Phenotypic Cytostatic selectivity ALA slows cancer cell cycling without universal apoptosis
6 Apoptosis ↑ apoptosis (conditional) ↓ apoptosis Phenotypic Threshold-dependent death Occurs in cancer cells when redox stress exceeds buffering capacity
7 NRF2 antioxidant response ↑ NRF2 (adaptive, often insufficient) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 reflects attempted redox recovery; not a kill mechanism


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
3437- ALA,    Revisiting the molecular mechanisms of Alpha Lipoic Acid (ALA) actions on metabolism
- Review, Var, NA
*IronCh↑, *antiOx↑, *ROS↓, *GSH↑, *NF-kB↓, *AMPK⇅, *FAO↑, *GlucoseCon↑, *PI3K↑, *Akt?,
3283- ALA,    Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells
- in-vitro, Nor, NA
*TNF-α↓, *NF-kB↓, *antiOx↑, *IronCh↑, *GSSG↓, *VCAM-1↓, *E-sel↓, *ICAM-1↓, *MCP1↓, *NF-kB↓, IKKα↓,
3272- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*antiOx↑, *glucose↑, *eNOS↑, *NRF2↑, *MMP9↓, *VCAM-1↓, *NF-kB↓, *cardioP↑, *cognitive↑, *eff↓, *BBB↑, *IronCh↑, *GSH↑, *PKCδ↑, *ERK↑, *p38↑, *MAPK↑, *PI3K↑, *Akt↑, *PTEN↓, *AMPK↑, *GLUT4↑, *GLUT1↑, *Inflam↓,
3269- ALA,    Sulfur-containing therapeutics in the treatment of Alzheimer’s disease
- NA, AD, NA
*AChE↓, *GlucoseCon↑, *ACC↑, *GSH↑, *Aβ↓, *Catalase↑, *GSR↑, *GSTs↑, *NADPH↑, *NQO1↑, *iNOS↓, *NF-kB↓, *lipid-P↓, *BBB↑, *memory↑, *cognitive↑, *antiOx↑, *Inflam↓,
3549- ALA,    Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
- Review, AD, NA
*Inflam↓, *other↝, *other↝, *neuroP↑, *BioAv↝, *adiP↑, *BBB↑, *Casp6↓, *Casp9↓, *TNF-α↓, *IL6↓, *IL1β↓, *ROS↓, *NO↓, *iNOS↓, *COX2↓, *JNK↓, *p‑NF-kB↓, *Aβ↓, *BP↓, *memory↑, *cAMP↑, *ERK↑, *Akt↑, cognitive?,
3547- ALA,    Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration
- Review, AD, NA - Review, Park, NA
*memory↑, *neuroP↑, *motorD↑, *VitC↑, *VitE↑, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *5HT↑, *lipid-P↓, *IronCh↑, *AChE↓, *Inflam↓, *GlucoseCon↑, *GLUT3↑, *GLUT4↑, NF-kB↓, *IGF-1↑, *IL1β↓, *TNF-α↓, *cognitive↑, *ChAT↑, *HO-1↑, *NQO1↑,
3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, *Inflam↓, *VCAM-1↓, *5HT↑, *memory↑, *BioAv↝, *Half-Life↓, *NF-kB↓, *antiOx↑, *IronCh↑, *ROS↓, *ATP↑, *ChAT↑, *Ach↑, *cognitive↑, *lipid-P↓, *VitC↑, *VitE↑, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *Aβ↓,
3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, *IronCh↑, *GSH↑, *antiOx↑, *NRF2↑, *MMP9↓, *VCAM-1↓, *NF-kB↓, *cognitive↑, *Inflam↓, *BioAv↝, *BioAv↝, *BBB↑, *H2O2∅, *neuroP↑, *PKCδ↑, *ERK↑, *MAPK↑, *PI3K↑, *Akt↑, *PTEN↓, *AMPK↑, *GLUT4↑, *GlucoseCon↑, *BP↝, *eff↑, *ICAM-1↓, *VCAM-1↓, *Dose↝,
3456- ALA,    Renal-Protective Roles of Lipoic Acid in Kidney Disease
- Review, NA, NA
*RenoP↑, *ROS↓, *antiOx↑, *Inflam↓, *Sepsis↓, *IronCh↑, *BUN↓, *creat↓, *TNF-α↓, *IL6↓, *IL1β↓, *MDA↓, *NRF2↑, *HO-1↑, *NQO1↑, *chemoP↑, *eff↑, *NF-kB↓,
3451- ALA,    Alpha-lipoic acid ameliorates H2O2-induced human vein endothelial cells injury via suppression of inflammation and oxidative stress
- in-vitro, Nor, HUVECs
*LDH↓, *NOX4↓, *NF-kB↓, *iNOS↓, *VCAM-1↓, *ICAM-1↓, *ROS↓, *cardioP↑,
3450- ALA,    α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells
- in-vitro, NA, AGS
*IL8↓, *MAPK↓, *JAK↓, *STAT↓, *NF-kB↓,
3449- ALA,    Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells
- in-vitro, AD, SK-N-BE
*antiOx↑, *NRF2↑, *NF-kB↓, *IL1β↓, *IL6↓, neuroP↑,
272- ALA,    Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function
- in-vitro, NA, HUVECs
NF-kB↓,
278- ALA,    The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment
- Review, NA, NA
ROS↑, NRF2↑, Inflam↓, frataxin↑, *BioAv↓, ChemoSen↑, Hif1a↓, eff↑, FAK↓, ITGB1↓, MMP2↓, MMP9↓, EMT↓, Snail↓, Vim↓, Zeb1↓, P53↑, MGMT↓, Mcl-1↓, Bcl-xL↓, Bcl-2↓, survivin↓, Casp3↑, Casp9↑, BAX↑, p‑Akt↓, GSK‐3β↓, *antiOx↑, *ROS↓, selectivity↑, angioG↓, MMPs↓, NF-kB↓, ITGB3↓, NADPH↓,

Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

frataxin↑, 1,   NRF2↑, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 1,   Casp9↑, 1,   Mcl-1↓, 1,   survivin↓, 1,  

DNA Damage & Repair ⓘ

MGMT↓, 1,   P53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   GSK‐3β↓, 1,  

Migration ⓘ

FAK↓, 1,   ITGB1↓, 1,   ITGB3↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Snail↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Immune & Inflammatory Signaling ⓘ

IKKα↓, 1,   Inflam↓, 1,   NF-kB↓, 3,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,   selectivity↑, 1,  

Functional Outcomes ⓘ

cognitive?, 1,   neuroP↑, 1,  
Total Targets: 35

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 9,   Catalase↑, 3,   GPx↑, 2,   GSH↑, 6,   GSR↑, 1,   GSSG↓, 1,   GSTs↑, 1,   H2O2∅, 1,   HO-1↑, 2,   lipid-P↓, 3,   MDA↓, 1,   NOX4↓, 1,   NQO1↑, 3,   NRF2↑, 4,   ROS↓, 7,   SOD↑, 2,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 7,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   adiP↑, 1,   AMPK↑, 2,   AMPK⇅, 1,   BUN↓, 1,   cAMP↑, 1,   FAO↑, 1,   glucose↑, 1,   GlucoseCon↑, 4,   LDH↓, 1,   NADPH↑, 1,  

Cell Death ⓘ

Akt?, 1,   Akt↑, 3,   Casp6↓, 1,   Casp9↓, 1,   iNOS↓, 3,   JNK↓, 1,   MAPK↓, 1,   MAPK↑, 2,   p38↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↝, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 3,   IGF-1↑, 1,   PI3K↑, 3,   PTEN↓, 2,   STAT↓, 1,  

Migration ⓘ

E-sel↓, 1,   MMP9↓, 2,   PKCδ↑, 2,   VCAM-1↓, 6,  

Angiogenesis & Vasculature ⓘ

eNOS↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 4,   GLUT1↑, 1,   GLUT3↑, 1,   GLUT4↑, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   ICAM-1↓, 3,   IL1β↓, 4,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 7,   JAK↓, 1,   MCP1↓, 1,   NF-kB↓, 11,   p‑NF-kB↓, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission ⓘ

5HT↑, 2,   AChE↓, 2,   ChAT↑, 2,  

Protein Aggregation ⓘ

Aβ↓, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 4,   Dose↝, 1,   eff↓, 1,   eff↑, 2,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   BP↝, 1,   creat↓, 1,   IL6↓, 3,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoP↑, 1,   cognitive↑, 5,   memory↑, 4,   motorD↑, 1,   neuroP↑, 4,   RenoP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 91

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
14 Alpha-Lipoic-Acid
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#:29  Target#:214  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page