Crocetin / LDH Cancer Research Results

Cro, Crocetin: Click to Expand ⟱
Features:
Crocetin is a carotenoid pigment found in saffron (Crocus sativus) and has been studied for its potential anti-cancer properties. Research has shown that crocetin may have anti-tumor and anti-proliferative effects, inhibiting the growth of various types of cancer cells.
Crocetin is a carotenoid dicarboxylic acid derived from saffron (Crocus sativus) and is a metabolite of crocin. It is lipophilic and more bioavailable than crocin. In cancer research, crocetin is studied mainly in preclinical models, where it appears to influence apoptosis, inflammation, angiogenesis, and redox signaling. It is not a primary cytotoxic chemotherapeutic, but a signaling and stress-modulating compound.
Mechanistic themes reported:
-NF-κB suppression
-PI3K/AKT pathway modulation
-MAPK signaling effects
-Apoptosis induction (mitochondrial pathway)
-Anti-angiogenic signaling (VEGF reduction)
-Redox modulation (context-dependent antioxidant / pro-oxidant behavior)

Evidence level: predominantly cell culture and animal models.
Reported to modulate glycolytic metabolism and lactate production (model-dependent); not established as a direct LDH enzymatic inhibitor

Crocetin (Cro) — Cancer-Oriented Time-Scale Flagged Pathway Table
Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 Intrinsic apoptosis (mitochondrial pathway) Bax ↑; Bcl-2 ↓; caspases ↑ (reported) ↔ (less activation) G Cell death signaling Apoptosis induction via mitochondrial membrane disruption is one of the most frequently reported tumor effects.
2 NF-κB inflammatory signaling NF-κB ↓; cytokines/COX-2 ↓ (reported) Inflammation tone ↓ R, G Anti-inflammatory modulation Reduction of inflammatory transcription may contribute to anti-proliferative and anti-invasive effects.
3 PI3K / AKT survival pathway AKT phosphorylation ↓ (reported; model-dependent) ↔ R, G Growth suppression Observed in several tumor cell systems; should be presented as context-dependent.
4 MAPK signaling (ERK / JNK / p38) Stress MAPK modulation (variable direction) ↔ P, R, G Signal reprogramming JNK activation and ERK suppression have been reported in some models; effects vary by cell type.
5 ROS / redox modulation ROS ↑ (pro-apoptotic) or ROS ↓ (antioxidant) depending on dose Oxidative stress ↓ (protective models) P, R, G Redox modulation (biphasic) Crocetin can behave as antioxidant in normal cells and pro-oxidant in tumor contexts at higher concentrations.
6 Cell-cycle arrest G0/G1 or G2/M arrest ↑ (reported) ↔ G Cytostasis Often secondary to survival pathway suppression and stress signaling.
7 Angiogenesis signaling (VEGF) VEGF ↓; angiogenic signaling ↓ (reported) ↔ G Anti-angiogenic support Observed in some in vitro and animal tumor models; typically secondary to NF-κB/AKT changes.
8 Metabolic reprogramming (glycolysis tone) Lactate ↓ (reported; indirect) ↔ R, G Warburg modulation (indirect) No strong evidence for direct LDH enzyme inhibition; effects likely secondary to survival/redox signaling changes.
9 Migration / invasion (MMPs) MMP2/MMP9 ↓; invasion ↓ (reported) ↔ G Anti-invasive phenotype Reported reduction in metastasis markers in certain systems.
10 Chemo-sensitization (adjunct potential) Therapy sensitivity ↑ (reported in some combinations) Normal tissue protection possible G Adjunct modulation May enhance cytotoxic response in some models; data are preclinical.
11 Translation constraint Clinical anti-cancer efficacy not established Generally well tolerated in dietary contexts — Evidence limitation Human oncology data are limited; dosing and bioavailability remain practical considerations.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (early redox and signaling interactions)
  • R: 30 min–3 hr (NF-κB / PI3K / MAPK modulation)
  • G: >3 hr (apoptosis, angiogenesis, and phenotype-level outcomes)
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.



Scientific Papers found: Click to Expand⟱
945- Cro,    Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer
- in-vitro, Lung, A549 - in-vitro, Cerv, HeLa
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:


Core Metabolism/Glycolysis ⓘ

LDH↓, 1,  

Clinical Biomarkers ⓘ

LDH↓, 1,  
Total Targets: 2

Pathway results for Effect on Normal Cells:


Total Targets: 0

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:%  Cells:%  prod#:249  Target#:906  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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