Alpha-Lipoic-Acid / ROS 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↓">ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : 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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
375- AgNPs,  ALA,    Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer
- in-vitro, PC, Bxpc-3 - in-vitro, PC, PANC1 - in-vitro, PC, MIA PaCa-2 - in-vivo, NA, NA
mtDam↑, ROS↑, *toxicity↓, Dose∅, selectivity↑,
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?,
3447- ALA,    Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells
- in-vitro, AD, SH-SY5Y
*ATP↑, *MMP↑, *ROS↓, *GlucoseCon↑, *GSH↑, *neuroP↑, *cognitive↑, *Ach↑, *Inflam↓, *Aβ↓, OXPHOS↓,
3446- ALA,  CUR,    The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression
- in-vivo, Nor, NA
*hepatoP↑, *α-SMA↓, *COL3A1↓, *ROS↓, *GSH↑, *ALAT↓, *AST↓, *ALP↓, *MDA↓,
3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *IronCh↑, *cognitive↑, *cardioP↓, AntiCan↑, *neuroP↑, *Inflam↓, *BioAv↓, *AntiAge↑, *Half-Life↓, *BioAv↝, other↝, EGFR↓, Akt↓, ROS↓, TumCCA↑, p27↑, PDH↑, Glycolysis↓, ROS↑, *eff↑, *memory↑, *motorD↑, *GutMicro↑,
3442- ALA,    α‑lipoic acid modulates prostate cancer cell growth and bone cell differentiation
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B - in-vitro, Nor, 3T3
tumCV↓, TumCMig↓, TumCI↓, ROS↑, Hif1a↑, JNK↑, Casp↑, TumCCA↑, Apoptosis↑, selectivity↑,
3440- ALA,    Protective effects of alpha lipoic acid (ALA) are mediated by hormetic mechanisms
- Review, AD, NA
*ROS↓, *neuroP↑, *Aβ↓, *cardioP?,
3439- ALA,    The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles
- in-vitro, NA, NA
*ROS↓, *TAC↑, *eff↑, *SOD↑, *GPx↑, *Catalase↑, *GlucoseCon↑, *antiOx↑,
3438- ALA,    The Potent Antioxidant Alpha Lipoic Acid
- Review, NA, NA - Review, AD, NA
*antiOx↑, *cardioP↑, *cognitive↑, *AntiAge↑, *Inflam↓, *AntiCan↑, *neuroP↑, *IronCh↑, *ROS↑, *Weight↓, *Ach↑, *ROS↓, *GSH↑, *lipid-P↓, *memory↑, *NRF2↑, *ChAT↑, *GlucoseCon↑, *Acetyl-CoA↑,
3448- ALA,    Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line
*Inflam↓, *ROS↓, *GSH↑, *GPx↑, *Casp3↓, *Casp9↓, *MMP↑,
3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF-7
ChemoSen↑, PI3K↓, Akt↓, ATP↓, GlucoseCon↓, ROS↑, PKM2↓, Glycolysis↓, CSCs↓, IGF-1R↓, Furin↓, RadioS↑,
3434- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓, PI3K↓, p‑Akt↓, p‑P70S6K↓, mTOR↓, ATP↓, GlucoseCon↓, ROS↑, PKM2↓, LDHA↓, Glycolysis↓, ChemoSen↑,
3433- ALA,    Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
*ROS↓, *Apoptosis↓, *Hif1a↑, *FOXO1↑, *FOXO3↑, *ATM↑, *SIRT1↑, *SIRT3↑, *CD34↑,
3284- ALA,    Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA
- vitro+vivo, Park, NA
*antiOx↑, *IronCh↑, *neuroP↑, *ROS↓, *Iron↓, *BBB↑, *motorD↑, *GSH↑,
3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, *memory↑, *neuroP↑, *Inflam↓, *IronCh↑, *NRF2↑, *BBB↑, *GlucoseCon↑, *Ach↑, *ROS↓, *p‑tau↓, *Aβ↓, *cognitive↑, *Hif1a↑, *Ca+2↓, *GLUT3↑, *GLUT4↑, *HO-1↑, *VEGF↑, *PDKs↓, *PDH↑, *VCAM-1↓, *GSH↑, *NRF2↑, *hepatoP↑, *ChAT↑,
3270- ALA,    Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis
- Trial, AD, NA
*cognitive↑, *other↝, *neuroP↑, *IronCh↑, *ROS↓, *GSH↑,
3543- ALA,    The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease
- Study, AD, NA
*cognitive↑, *antiOx↑, *Inflam↓, *neuroP↑, *Ach↑, *ROS↓, *GlucoseCon↑, *lipid-P↓, *GSH↑, *Acetyl-CoA↑,
3550- ALA,    Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?
- Review, AD, NA
*antiOx↑, *Inflam↓, *PGE2↓, *COX2↓, *iNOS↓, *TNF-α↓, *IL1β↓, *IL6↓, *BioAv↓, *Ach↑, *ROS↓, *cognitive↑, *neuroP↑, *BBB↑, *Half-Life↓, *BioAv↑, *Casp3↓, *Casp9↓, *ChAT↑, *cognitive↑, *eff↑, *cAMP↑, *IL2↓, *INF-γ↓, *TNF-α↓, *SIRT1↑, *SOD↑, *GPx↑, *MDA↓, *NRF2↑,
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?,
3548- ALA,    How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease
- Review, AD, NA
*BBB↑, *other↑, *other↑, *DHA↑, *neuroP↑, *ROS↓, *other?,
3546- ALA,    Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study
- Study, AD, NA
*antiOx↑, *ROS↓, *cognitive∅, *lipid-P↓, *memory↑, *ChAT↑, *Acetyl-CoA↑, *Aβ↓, *BioAv↑, *BBB↑, *toxicity∅,
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↓,
3544- ALA,    Alpha lipoic acid for dementia
- Review, AD, NA
*antiOx↑, *BBB↑, *VitC↑, *VitE↑, *GSH↑, *IronCh↑, *neuroP↑, *NO↓, *cognitive↑, *AntiAge↑, *memory↑, *ROS↓,
259- ALA,    Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells
- in-vitro, Liver, HepG2 - in-vitro, Liver, FaO
Cyc↓, P21↑, ROS↑, p‑P53↑, BAX↑, Cyt‑c↑, Casp↑, survivin↓, JNK↑, Akt↓,
3541- ALA,    Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
- Review, Var, NA
*antiOx↑, *IronCh↑, *GSH↑, *BBB↑, Apoptosis↑, MMP↓, ROS↑, lipid-P↑, PARP1↑, Casp3↑, Casp9↑, *NRF2↑, *GSH↑, *ROS↓, RenoP↑, ChemoSen↑, *BG↓,
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↓,
3454- ALA,    Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
TumCG↑, Glycolysis↓, ROS↑, CSCs↓, selectivity↑, LC3B-II↑, MMP↓, mitResp↓, ATP↓, OCR↓, NAD↓, p‑AMPK↑, GlucoseCon↓, lactateProd↓, HK2↓, PFK↓, LDHA↓, eff↓, mTOR↓, ECAR↓, ALDH↓, CD44↓, CD24↓,
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↑,
281- ALA,    Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation
- in-vitro, Lung, H460
mt-ROS↑, Apoptosis↑, Casp9↑, Bcl-2↓, eff↓, eff↑, H2O2↑, Dose↑,
279- ALA,    Lipoic acid-induced oxidative stress abrogates IGF-1R maturation by inhibiting the CREB/furin axis in breast cancer cell lines
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Furin↓, IGF-1R↓, ROS↑, CREB↓, Furin↓, IGF-1R↓,
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↓,
277- ALA,    α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B
ROS↑, Hif1a↑, JNK↑, Casp3↑, P21↑, BAX↑, Bcl-xL↓, cFos↓,
267- ALA,    α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells
- vitro+vivo, Lung, A549 - vitro+vivo, Lung, PC9
Apoptosis↑, ROS↑, PDK1↓, NRF2↓, PDK1↓, Bcl-2↓, Casp9↑, Dose∅,
266- ALA,    Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death
- in-vitro, Ovarian, IGROV1
Mcl-1↓, Bcl-xL↓, BIM↑, ROS↑,
265- ALA,    Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
ROS↓, SOD↓, GSTP1/GSTπ↓, NRF2↓, p62↓, p62↑, SOD↑, p‑mTOR↑, Beclin-1↓, ROS↑, SOD1↑,
264- ALA,    α-Lipoic acid induces Endoplasmic Reticulum stress-mediated apoptosis in hepatoma cells
- in-vitro, HCC, FaO
ROS↑, P53↑, ER Stress↑, UPR↑, CHOP↑, PDI↑, GRP78/BiP↑, GRP58↓,
261- ALA,    The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells
- in-vitro, BC, MCF-7
ROS↓, Akt↓, p27↑, Bax:Bcl2↑,
304- ALA,    alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation
- in-vitro, Colon, HT-29
mt-ROS↑, Apoptosis↑, Casp3↑, DNAdam↑, Bcl-xL↓, Dose↝,
297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, TumCG↓, ROS↑, AMPK↑, EGR4↓, Half-Life↓, BioAv↝, *GSH↑, *IronCh↑, *ROS↓, *antiOx↑, *neuroP↑, *Ach↑, *lipid-P↓, *IL1β↓, *IL6↓, TumCP↓, FDG↓, Apoptosis↑, AMPK↑, mTOR↓, EGFR↓, TumCI↓, TumCMig↓, *memory↑, *BioAv↑, *BioAv↝, *other↓, *other↝, *Half-Life↓, *BioAv↑, *ChAT↑, *GlucoseCon↑,
1235- ALA,  Cisplatin,    α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway
- in-vitro, Nor, HEI-OC1 - ex-vivo, NA, NA
ROS↑, HO-1↓, *toxicity↓, chemoP↑, *ROS↓, *HO-1↑, *SOD1↑, *NRF2↑,
1628- HCA,  ALA,    Addition of Hydroxy Citrate improves effect of ALA
- Review, Var, NA
ACLY↓, other↓, ROS↑, eff↑, PDKs↓,

Showing Research Papers: 1 to 42 of 42

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 42

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

frataxin↑, 1,   GSTP1/GSTπ↓, 1,   H2O2↑, 1,   HO-1↓, 1,   lipid-P↑, 1,   NRF2↓, 2,   NRF2↑, 1,   OXPHOS↓, 1,   ROS↓, 3,   ROS↑, 18,   mt-ROS↑, 2,   SOD↓, 1,   SOD↑, 1,   SOD1↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 3,   mitResp↓, 1,   MMP↓, 2,   mtDam↑, 1,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   AMPK↑, 2,   p‑AMPK↑, 1,   CREB↓, 1,   ECAR↓, 1,   FDG↓, 1,   GlucoseCon↓, 3,   Glycolysis↓, 4,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 2,   NAD↓, 1,   NADPH↓, 1,   PDH↑, 2,   PDK1↓, 2,   PDKs↓, 1,   PFK↓, 1,   PKM2↓, 2,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↓, 2,   Apoptosis↑, 6,   BAX↑, 3,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 4,   BIM↑, 1,   Casp↑, 2,   Casp3↑, 4,   Casp9↑, 4,   Cyt‑c↑, 1,   GRP58↓, 1,   JNK↑, 3,   Mcl-1↓, 2,   p27↑, 2,   survivin↓, 2,  

Transcription & Epigenetics ⓘ

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

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   LC3B-II↑, 1,   p62↓, 1,   p62↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   MGMT↓, 1,   P53↑, 2,   p‑P53↑, 1,   PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

Cyc↓, 1,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CD24↓, 1,   CD44↓, 1,   cFos↓, 1,   CSCs↓, 2,   EMT↓, 1,   GSK‐3β↓, 1,   IGF-1R↓, 3,   mTOR↓, 3,   p‑mTOR↑, 1,   p‑P70S6K↓, 1,   PI3K↓, 2,   TumCG↓, 1,   TumCG↑, 1,  

Migration ⓘ

FAK↓, 1,   Furin↓, 3,   ITGB1↓, 1,   ITGB3↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Snail↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 2,   EGR4↓, 1,   Hif1a↓, 1,   Hif1a↑, 2,   PDI↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 4,   Dose↑, 1,   Dose↝, 1,   Dose∅, 2,   eff↓, 2,   eff↑, 3,   Half-Life↓, 1,   RadioS↑, 1,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

EGFR↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 1,   cognitive?, 1,   RenoP↑, 1,  
Total Targets: 123

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 16,   Catalase↑, 2,   GPx↑, 4,   GSH↑, 15,   H2O2∅, 1,   HO-1↑, 3,   Iron↓, 1,   lipid-P↓, 5,   MDA↓, 3,   NOX4↓, 1,   NQO1↑, 1,   NRF2↑, 8,   ROS↓, 26,   ROS↑, 1,   SIRT3↑, 1,   SOD↑, 3,   SOD1↑, 1,   TAC↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 12,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,   MMP↑, 2,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↑, 3,   adiP↑, 1,   ALAT↓, 1,   AMPK↑, 1,   AMPK⇅, 1,   BUN↓, 1,   cAMP↑, 2,   DHA↑, 1,   FAO↑, 1,   GlucoseCon↑, 8,   LDH↓, 1,   PDH↑, 1,   PDKs↓, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt?, 1,   Akt↑, 2,   Apoptosis↓, 1,   Casp3↓, 2,   Casp6↓, 1,   Casp9↓, 3,   iNOS↓, 3,   JNK↓, 1,   MAPK↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 7,   other?, 1,   other↓, 1,   other↑, 2,   other↝, 4,  

DNA Damage & Repair ⓘ

ATM↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD34↑, 1,   ERK↑, 2,   FOXO1↑, 1,   FOXO3↑, 1,   PI3K↑, 2,   PTEN↓, 1,  

Migration ⓘ

Ca+2↓, 1,   COL3A1↓, 1,   MMP9↓, 1,   PKCδ↑, 1,   VCAM-1↓, 5,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↑, 2,   NO↓, 2,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 9,   GLUT3↑, 1,   GLUT4↑, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 2,   IL1β↓, 4,   IL2↓, 1,   IL6↓, 4,   INF-γ↓, 1,   Inflam↓, 11,   NF-kB↓, 5,   p‑NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   ChAT↑, 6,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 6,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 4,   BioAv↝, 6,   Dose↝, 1,   eff↑, 5,   Half-Life↓, 4,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BG↓, 1,   BP↓, 1,   BP↝, 1,   creat↓, 1,   GutMicro↑, 1,   IL6↓, 4,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 3,   AntiCan↑, 1,   cardioP?, 1,   cardioP↓, 1,   cardioP↑, 2,   chemoP↑, 1,   cognitive↑, 11,   cognitive∅, 1,   hepatoP↑, 2,   memory↑, 8,   motorD↑, 2,   neuroP↑, 15,   RenoP↑, 1,   toxicity↓, 2,   toxicity∅, 1,   Weight↓, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 118

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
42 Alpha-Lipoic-Acid
1 Silver-NanoParticles
1 Curcumin
1 Cisplatin
1 HydroxyCitric 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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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