Alpha-Lipoic-Acid / Catalase 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↑">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

Lipoic Acid Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial redox and ROS ↑ mitochondrial ROS; ↔/↓ total ROS (context-dependent) ↓ ROS P/R Apoptosis and redox disruption Central but bidirectional mechanism. HT-29 and A549 models show pro-oxidant ROS-mediated death, whereas MCF-7 and some prostate models show ROS lowering with growth inhibition.
2 PI3K Akt survival signaling ↓ Akt; ↑ p27; ↓ proliferation ↔/↑ Akt (context-dependent) R/G Cell-cycle arrest and apoptosis Breast cancer studies demonstrate suppression of Akt with G1 arrest, Bax/Bcl-2 shift and apoptotic signaling.
3 Mitochondria and MPTP ↑ permeability transition; ↓ membrane potential; ↑ cytochrome c Generally protected from oxidative mitochondrial injury R Intrinsic apoptosis Provides a mechanistic bridge between altered mitochondrial metabolism, ROS production and caspase activation.
4 ER stress CHOP XBP1 ↑ GRP78; ↑ CHOP; ↑ XBP1; ↑ caspases Not established as a therapeutic effect R/G ER-stress-mediated apoptosis Demonstrated prominently in A549 lung cancer cells and substantially dependent on ROS.
5 Ca²⁺ and TRPV1 signaling ↑ Ca²⁺; ↑ TRPV1-dependent mitochondrial apoptosis Context-dependent P/R Apoptotic amplification Particularly evident with cisplatin; Ca²⁺ has also been implicated in ALA-induced lung-cancer apoptosis.
6 Bax Bcl-2 caspase axis ↑ Bax; ↓ Bcl-2/Bcl-XL; ↑ caspase-3/9; ↑ PARP cleavage Often ↓ inappropriate apoptosis during oxidative injury R/G Apoptosis Downstream convergence point for multiple ALA-responsive pathways.
7 KEAP1 NRF2 p62 ↓ NRF2/p62 in selected prostate models ↑ NRF2; ↑ HO-1/SOD antioxidant defense R/G Context-dependent redox regulation NRF2 should not be classified simply as increased or decreased. ALA activates protective NRF2 signaling in normal cells but can suppress NRF2 in some malignant cells.
8 Glutathione redox system ↑ GSH in some models; ↓ functional antioxidant defense during pro-oxidant killing (context-dependent) ↑ GSH; ↑ GSH/GSSG ratio; ↑ antioxidant protection R/G Redox buffering and context-dependent modulation of apoptosis ALA/DHLA can increase intracellular GSH and stimulate GSH synthesis, particularly in normal or oxidatively stressed cells. In cancer cells, however, increased GSH can oppose ROS-dependent ALA cytotoxicity; several anticancer models instead show ROS accumulation or suppression of antioxidant enzymes. Therefore GSH is mechanistically important but not uniformly anticancer.
9 Autophagy mTOR Beclin-1 LC3 ↓ Beclin-1; ↓ LC3; ↓ autophagy in prostate models Context-dependent G Reduced cancer-cell survival ALA-associated ↑ mTOR and inhibition of autophagy have been reported in LNCaP and DU-145 cells; not established as universal.
10 NF-κB IKK inflammatory signaling ↓ NF-κB (model-dependent) ↓ inflammatory NF-κB activation R/G Reduced survival and inflammatory signaling ALA can inhibit IKK/NF-κB independently of its antioxidant activity, but much of the evidence is from non-malignant experimental systems.
11 Integrin FAK EMT invasion ↓ β1-integrin/FAK; ↓ MMP-2/MMP-9; ↓ EMT Not established G Reduced migration and invasion Preclinical evidence supports antimetastatic effects, but systemic clinical relevance has not been established.
12 Chemosensitization ↑ cisplatin-associated ROS, Ca²⁺ and apoptosis (model-dependent) ↓ chemotherapy-associated oxidative injury in several normal tissues R/G Potential selective treatment modulation ALA can enhance cisplatin cytotoxicity in cultured cancer cells while protecting normal tissue in other models. Clinical net effect on antitumor efficacy is unresolved.
13 Radiosensitivity and radioprotection ↔ antitumor radiosensitization not established ↓ radiation-induced ROS and tissue injury R/G Predominantly radioprotection Human and preclinical literature is oriented toward mitigation of normal-tissue radiation toxicity rather than tumor radiosensitization.
14 Clinical Translation Constraint Common experimental concentrations exceed oral systemic exposure Systemic antioxidant effects occur at clinically used doses G Limits direct anticancer translation Oral bioavailability is approximately 30%, elimination is rapid, and many cancer experiments use 250–1000 µM compared with transient human plasma concentrations typically in the low tens of micromolar.

P: 0–30 min    R: 30 min–3 hr    G: >3 hr

Lipoic acid and Alzheimer’s disease — ALA has sufficient AD-specific mechanistic and human evidence to justify a separate database section, although efficacy remains unproven. Its rationale includes mitochondrial cofactor activity, reduction of oxidative stress, regeneration of endogenous antioxidants, modulation of inflammatory signaling and potential improvement of neuronal glucose/energy metabolism. Small open-label studies using 600 mg/day reported slower cognitive decline, while a small randomized trial of omega-3 plus 600 mg/day ALA found less decline in selected MMSE and instrumental-ADL outcomes but no benefit in its primary oxidative-stress endpoint or ADAS-cog. Another randomized antioxidant combination containing 900 mg/day ALA produced an unexpected greater MMSE decline, making the clinical evidence mixed and insufficient for therapeutic conclusions.

Clinical evidence status: Small human / pilot RCT / adjunct use. No adequately powered confirmatory trial establishes ALA as a disease-modifying treatment for Alzheimer’s disease.

Lipoic Acid in Alzheimer’s Disease

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Oxidative stress and glutathione redox cycling ↓ ROS; ↑ antioxidant capacity Neuroprotection ALA/DHLA can scavenge oxidants and regenerate endogenous antioxidant systems; biologically plausible but clinical disease modification is unproven.
2 Mitochondrial energy metabolism ↑ mitochondrial cofactor function Support of neuronal bioenergetics Lipoyl groups are essential cofactors for pyruvate and α-ketoglutarate dehydrogenase complexes.
3 NRF2 antioxidant response ↑ NRF2-associated antioxidant defense Reduced oxidative injury Well supported mechanistically in non-cancer tissues but direct AD clinical validation is limited.
4 NF-κB inflammatory signaling ↓ NF-κB Reduced neuroinflammatory signaling Mechanistically plausible; much supporting evidence is indirect rather than from human AD brain studies.
5 Cognitive and functional decline ↔/↓ decline (study-dependent) Possible clinical neuroprotection Small open-label and omega-3 plus ALA studies produced signals of benefit, but larger confirmatory evidence is lacking and antioxidant-combination data include a possible adverse cognitive signal.


Catalase, Catalase: Click to Expand ⟱
Source:
Type:
Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.
Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer.
Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA.

Catalase and Cancer
Oxidative Stress and Cancer:
Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis.
Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells.
Expression Levels in Different Cancers:
Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior.
Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis.
Prognostic Implications:
Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress.

Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched).
Scientific Papers found: Click to Expand⟱
3439- ALA,    The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles
- in-vitro, NA, NA
*ROS↓, At 96 h after culture, a decrease in ROS and an increase in TAC were observed in ALA group compared to control group (p < 0.05).
*TAC↑,
*eff↑, ALA (100 uM) improves the in vitro development of follicles. This effect may be mediated by decreasing ROS concentration and increasing follicular TAC level during the culture period.‎‎‎
*SOD↑, ALA administration significantly elevated plasma total antioxidant status and could increase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in the brain tissues of male rat exposed to restraint stress
*GPx↑,
*Catalase↑,
*GlucoseCon↑, ALA enhances glucose uptake by cells,
*antiOx↑, Taken together, our study indicates that ALA has an excellent antioxidant activity,

3269- ALA,    Sulfur-containing therapeutics in the treatment of Alzheimer’s disease
- NA, AD, NA
*AChE↓, ALA activated AChE and increased glucose uptake, thus providing more acetyl-CoA to generate acetylcholine (ACh). (note activated AChE in this review likely should say inhibited!!!)
*GlucoseCon↑,
*ACC↑,
*GSH↑, ALA increased intracellular GSH levels by chelating redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and Aβ aggregation.
*Aβ↓,
*Catalase↑, Levels of several antioxidant enzymes including catalase, GR, glutathione-S-transferase (GST), NADPH, and quinone oxidoreductase-1 (NQO1) were enhanced by ALA
*GSR↑,
*GSTs↑,
*NADPH↑,
*NQO1↑,
*iNOS↓, LA prevented the induction of iNOS, inhibited TNFα-induced activation of NF-κB [42], levels of which are increased in AD.
*NF-kB↓,
*lipid-P↓, ALA reduced the levels of lipid peroxidation products
*BBB↑, ALA could easily cross the blood–brain barrier (BBB)
*memory↑, ALA treatment significantly improved the spatial memory and cognition capacity of the mice in the Morris water maze and novel object recognition test.
*cognitive↑,
*antiOx↑, antioxidant and anti-inflammatory activities of ALA
*Inflam↓,

3547- ALA,    Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration
- Review, AD, NA - Review, Park, NA
*memory↑, a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect
*neuroP↑,
*motorD↑, Improved motor dysfunction
*VitC↑, elevates the activities of antioxidants such as ascorbate (vitamin C), α-tocoferol (vitamin E) (Arivazhagan and Panneerselvam, 2000), glutathione (GSH)
*VitE↑,
*GSH↑,
*SOD↑, superoxide dismutase (SOD) activity (Arivazhagan et al., 2002; Cui et al., 2006; Militao et al., 2010), catalase (CAT) (Arivazhagan et al., 2002; Militao et al., 2010), glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*5HT↑, ↑levels of neurotransmitters (dopamine, serotonin and norepinephrine) in various brain regions
*lipid-P↓, ↓ level of lipid peroxidation,
*IronCh↑, ↓cerebral iron levels,
*AChE↓, ↓ AChE activity, ↓ inflammation
*Inflam↓,
*GlucoseCon↑, ↑brain glucose uptake; ↑ in the total GLUT3 and GLUT4 in the old mice;
*GLUT3↑,
*GLUT4↑,
NF-kB↓, authors showed that LA inhibited the stimulation of nuclear factor-κB (NF-κB)
*IGF-1↑, LA restored the parameters of total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Mahboob et al. (2016), analyzed the effects of LA in AlCl3- model of neurodegeneration,
*IL1β↓,
*TNF-α↓, Suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α) followed inhibition of cleaved caspase-3
*cognitive↑, demonstrating its capacity in ameliorating cognitive functions and enhancing cholinergic system functions
*ChAT↑, LA treatment increased the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) relative to AlCl3-treated group.
*HO-1↑, R-LA and S-LA also enhanced expression of genes related to anti-oxidative response such as heme oxygenase-1 (HO-1) and phase II detoxification enzymes such as NAD(P)H:Quinone Oxidoreductase 1 (NQO1).
*NQO1↑,

3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron, zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Immune & Inflammatory Signaling(tgid=16) ⓘ

NF-kB↓, 1,  
Total Targets: 1

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 3,   Catalase↑, 4,   GPx↑, 3,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 3,   NQO1↑, 2,   ROS↓, 2,   SOD↑, 3,   TAC↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACC↑, 1,   GlucoseCon↑, 3,   NADPH↑, 1,  

Cell Death(tgid=5) ⓘ

iNOS↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

IGF-1↑, 1,  

Migration(tgid=13) ⓘ

VCAM-1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   GLUT3↑, 1,   GLUT4↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL1β↓, 1,   Inflam↓, 3,   NF-kB↓, 2,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↑, 2,   AChE↓, 2,   ChAT↑, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,   eff↑, 1,   Half-Life↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cognitive↑, 3,   memory↑, 3,   motorD↑, 1,   neuroP↑, 2,  
Total Targets: 41

Scientific Paper Hit Count for: Catalase, Catalase
4 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#:46  State#:%  Dir#:%
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