LDH Cancer Research Results

LDH, Lactate Dehydrogenase: Click to Expand ⟱
Source:
Type:
LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits.
LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels.
leakage of LDH is a well-known indicator of cell membrane integrity and cell viability [35]. LDH leakage results from the breakdown of the plasma membrane and alterations in membrane permeability, and is widely used as a cytotoxicity endpoint.

However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism.

Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis.

Inhibitors:
Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors.
LDH is used as a clinical biomarker for Synthetic liver function, nutrition


Tier A — Direct LDH Enzyme Inhibitors (Validated Catalytic Inhibition)

Rank Compound Type LDH Target Potency Level Primary Effect Notes
1 NCI-006 Research drug LDHA / LDHB High (in vivo active) Potent glycolysis suppression Modern benchmark LDH inhibitor used in metabolic oncology models.
2 (R)-GNE-140 Research drug LDHA (±LDHB) High (nM range reported) Lactate production ↓ Widely used experimental LDH inhibitor.
3 FX11 Research drug LDHA High (μM range) Metabolic crisis in LDHA-dependent tumors Classic LDHA inhibitor; often increases ROS secondary to metabolic stress.
4 Oxamate Tool compound LDH (pyruvate-competitive) Moderate (mM cellular use) Reduces lactate flux Classical LDH inhibitor; requires high concentrations in cells.
5 Gossypol Natural product derivative LDHA Moderate–High Glycolysis inhibition Also has other targets; safety considerations apply.
6 Galloflavin Natural compound LDH isoforms Moderate Lactate production ↓ One of the better-supported “natural-like” LDH inhibitors.

Tier B — Indirect LDH-Axis Modulators (Glycolysis / Lactate Reduction Without Confirmed Direct Catalytic Inhibition)

Rank Compound Mechanism Type LDH Claim Type Primary Axis Notes / Caution
1 Lonidamine MCT/MPC modulation Lactate axis inhibition Metabolic transport blockade Better classified as lactate/pyruvate transport modulator.
2 Stiripentol Repurposed drug LDH pathway modulation Metabolic axis modulation Emerging oncology interest; primarily neurological drug.
3 Quercetin Flavonoid Reported LDH inhibition (mixed evidence) NF-κB / PI3K modulation Often LDH-release confusion; direct enzymatic proof limited.
4 Ursolic acid Triterpenoid Reported LDH interaction Warburg modulation More credible as metabolic signaling modulator.
5 Fisetin Flavonoid Docking / indirect reports Apoptosis / survival signaling Enzyme inhibition not well validated.
6 Resveratrol Polyphenol Indirect glycolysis suppression AMPK / HIF-1α modulation Reduces lactate via upstream signaling.
7 Curcumin Polyphenol Indirect LDH expression modulation Inflammation + metabolic signaling Bioavailability limits translational strength.
8 Berberine Alkaloid Indirect metabolic modulation AMPK activation Closer to metformin-like metabolic pressure.
9 Honokiol Lignan Indirect glycolysis effects Survival pathway suppression Not validated as catalytic LDH inhibitor.
10 Silibinin Flavonolignan Mixed / indirect reports Inflammation + metabolic axis Often misclassified as LDH inhibitor.
11 Kaempferol Flavonoid Often LDH-release marker confusion Glucose transport / signaling Do not list as direct LDH inhibitor without enzyme data.
12 Oleanolic acid / Limonin / Allicin / Taurine Natural compounds Weak / indirect evidence General metabolic modulation Should not be categorized as true LDH inhibitors.

Tier A = Direct catalytic LDH inhibition (enzyme-level validation).
Tier B = Indirect lactate reduction or glycolytic modulation without strong catalytic inhibition evidence.
Important: LDH release assays (cell damage marker) are not proof of LDH enzymatic inhibition.



IBD, Inflammatory Bowel Disease: Click to Expand ⟱
Inflammatory Bowel Disease

The main pathways involved in IBD include intestinal barrier dysfunction, mucus barrier impairment, dysbiosis-driven innate immune activation, and persistent cytokine-mediated inflammation. Key barrier components such as ZO-1, occludin, claudins, and MUC2 are commonly disrupted, increasing epithelial permeability and microbial translocation. This promotes activation of inflammatory hubs including TNF-α, NF-κB, IL-1β, IL-6/STAT3, and IL-23/Th17, while JAK/STAT signaling integrates multiple cytokine inputs that sustain chronic mucosal injury. Together, these pathways drive epithelial damage, immune dysregulation, and failure of mucosal healing in ulcerative colitis and Crohn’s disease

Rank Pathway / Axis Representative Targets / Markers Typical Direction in IBD Main Relevance
1 Intestinal Barrier Integrity / Tight Junctions ZO-1 (TJP1), Occludin (OCLN), Claudins (especially CLDN2, CLDN1) ZO-1 ↓, OCLN ↓, barrier loosened; CLDN2 often ↑ Core barrier failure increases intestinal permeability, microbial entry, and chronic inflammation
2 Mucus Barrier / Goblet Cell Axis MUC2, goblet cells, antimicrobial peptides MUC2 and goblet protection often impaired Weak mucus defense exposes the epithelium to luminal bacteria and antigens
3 TNF-α Inflammatory Axis TNF-α, TNFR1, TNFR2 Major inflammatory driver and validated therapeutic target in IBD
4 NF-κB Signaling NF-κB, IKK, IκB, COX-2, iNOS Central transcriptional hub for cytokines, chemokines, and inflammatory amplification
5 IL-23 / Th17 Axis IL-23, IL-23R, IL-17A, IL-22, RORγt ↑ / dysregulated Important bridge between innate and adaptive immune inflammation
6 JAK / STAT Signaling JAK1, JAK2, TYK2, STAT3 ↑ / activated Integrates multiple cytokine signals that sustain mucosal inflammation
7 IL-6 / STAT3 Axis IL-6, IL-6R, gp130, STAT3 Supports inflammatory persistence, immune-cell survival, and epithelial injury signaling
8 IL-1β / Inflammasome Axis IL-1β, NLRP3, ASC, caspase-1 Promotes innate inflammation, cytokine escalation, and epithelial damage
9 Microbiota / Dysbiosis / PRR Signaling Dysbiosis, TLRs, MyD88, LPS-related signaling Dysregulated / activated Links altered microbiota to barrier loss and immune activation
10 Oxidative Stress / Redox Imbalance ROS, lipid peroxidation, MPO, antioxidant defenses ↑ oxidative stress Contributes to epithelial injury, inflammatory signaling, and impaired healing
11 Leukocyte Trafficking / Adhesion Integrins, MAdCAM-1, ICAM-1, VCAM-1, chemokines Drives immune-cell recruitment into inflamed intestinal tissue
12 Epithelial Apoptosis / Restitution / Mucosal Healing Caspases, repair pathways, epithelial proliferation and restitution markers Injury ↑, healing impaired Determines whether mucosal damage resolves or progresses to chronic disease
Rank Natural Product Best Fit in IBD Evidence Level Main Rationale Notes
1 Curcumin Mainly Ulcerative Colitis (UC) Best human evidence Strongest overall adjunctive clinical support among common natural products for active UC Anti-inflammatory; NF-κB / cytokines / oxidative stress; mucosal support
2 Indigo naturalis (Qing Dai) Mainly UC Strong efficacy, safety-limited Good human efficacy signals, but safety concerns lower practical rank Anti-colitic; immune/inflammatory modulation; use caution flag for safety
3 Boswellia serrata UC / colitis Older smaller human trials Suggestive remission data and anti-inflammatory relevance, but evidence base is limited 5-LOX / leukotrienes / inflammation / mucosal protection
4 Aloe vera gel Mild-to-moderate UC Small human trial signal Some human improvement signal, though not as strong as curcumin or indigo naturalis Mucosal soothing / anti-inflammatory / healing support
5 Andrographis paniculata / andrographolide Mostly UC Mixed human, stronger preclinical Mechanistically promising, but human benefit is less consistent NF-κB / cytokines / barrier and anti-inflammatory support
6 Carvacrol Experimental colitis / dysbiosis / barrier dysfunction Preclinical Promising anti-colitis terpene with anti-inflammatory, antioxidant, and microbiota-related effects Dysbiosis / intestinal barrier integrity / NF-κB / oxidative stress
7 Thymol Experimental colitis / barrier dysfunction Preclinical Promising anti-colitis terpene with cytokine suppression and NF-κB-related effects Dysbiosis / intestinal barrier integrity / NF-κB / COX-2 / oxidative stress
8 Carvacrol + Thymol Experimental colitis, dysbiosis, bile-acid modulation Preclinical, mechanistically strong Combination may be especially relevant due to microbiota and bile-acid pathway effects in DSS colitis Bifidobacterium / secondary bile acids / barrier support / anti-colitic signaling
9 Peppermint oil Supportive / experimental colitis / GI symptom relief Mainly preclinical for IBD; stronger IBS evidence Menthol-rich oil with anti-inflammatory, antispasmodic, and possible barrier-supportive effects, but limited direct human IBD evidence Menthol / TRP modulation / cytokines / oxidative stress / GI symptom support


Scientific Papers found: Click to Expand⟱
3040- SK,    Pharmacological Properties of Shikonin – A Review of Literature since 2002
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA
*Half-Life↝, *BioAv↓, *BioAv↑, *BioAv↑, *Inflam↓, *TNF-α↓, *other↑, *MPO↓, *COX2↓, *NF-kB↑, *STAT3↑, *antiOx↑, *ROS↓, *neuroP↑, *SOD↑, *Catalase↑, *GPx↑, *Bcl-2↑, *BAX↓, cardioP↑, AntiCan↑, NF-kB↓, ROS↑, PKM2↓, TumCCA↑, Necroptosis↑, Apoptosis↑, DNAdam↑, MMP↓, Cyt‑c↑, LDH↝,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ROS↑, 1,  

Mitochondria & Bioenergetics

MMP↓, 1,  

Core Metabolism/Glycolysis

LDH↝, 1,   PKM2↓, 1,  

Cell Death

Apoptosis↑, 1,   Cyt‑c↑, 1,   Necroptosis↑, 1,  

DNA Damage & Repair

DNAdam↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Immune & Inflammatory Signaling

NF-kB↓, 1,  

Clinical Biomarkers

LDH↝, 1,  

Functional Outcomes

AntiCan↑, 1,   cardioP↑, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   MPO↓, 1,   ROS↓, 1,   SOD↑, 1,  

Cell Death

BAX↓, 1,   Bcl-2↑, 1,  

Transcription & Epigenetics

other↑, 1,  

Proliferation, Differentiation & Cell State

STAT3↑, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   Inflam↓, 1,   NF-kB↑, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↑, 2,   Half-Life↝, 1,  

Functional Outcomes

neuroP↑, 1,  
Total Targets: 18

Scientific Paper Hit Count for: LDH, Lactate Dehydrogenase
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:58  Cells:%  prod#:%  Target#:906  State#:%  Dir#:4
wNotes=0 sortOrder:rid,rpid

 

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