Luteolin / ALDH1A1 Cancer Research Results

LT, Luteolin: Click to Expand ⟱

Features:

Luteolin a Flavonoid found in celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers.
-MDR1 expression, MMP-9, IGF-1 and Epithelial to mesenchymal transition.

-Note half-life 2–3 hours
BioAv low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
Pathways:
- induce ROS production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- 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↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Luteolin — Cancer vs Normal Cell Effects

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Label	Primary Interpretation	Notes
1	PI3K → AKT → mTOR axis	↓ AKT / ↓ mTOR signaling	↔ adaptive suppression	Driver	Loss of survival and growth signaling	Luteolin consistently suppresses PI3K/AKT signaling, explaining growth inhibition and apoptosis sensitization
2	NF-κB signaling	↓ NF-κB activation	↓ inflammatory NF-κB tone	Driver	Suppression of inflammatory survival transcription	NF-κB inhibition is a core, repeatedly observed luteolin effect
3	Reactive oxygen species (ROS)	↑ ROS (context- & dose-dependent)	↓ ROS / buffered	Conditional Driver	Biphasic redox modulation	Luteolin can act as a pro-oxidant in cancer cells while remaining antioxidant in normal cells
4	Mitochondrial integrity / intrinsic apoptosis	↓ ΔΨm; ↑ caspase activation	↔ preserved	Secondary	Execution of intrinsic apoptosis	Mitochondrial apoptosis follows signaling and redox stress
5	STAT3 signaling	↓ STAT3 activation	↔ minimal	Secondary	Loss of proliferative and stemness signaling	STAT3 suppression contributes to reduced invasion and CSC traits
6	Cell cycle regulation	↑ G1 or G2/M arrest	↔ spared	Phenotypic	Cytostatic growth control	Cell-cycle arrest reflects upstream pathway inhibition
7	Migration / invasion (EMT, MMP axis)	↓ migration & invasion	↔	Phenotypic	Anti-metastatic phenotype	Reduced EMT and protease activity limit invasiveness

ALDH1A1, Aldehyde Dehydrogenase 1A1: Click to Expand ⟱

Source:

Type: Protein-coding gene

(ALDH1A1) is a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. Aldehyde dehydrogenases are the cancer stem cells which plays a role in CSC progression. ALDH comprise 19 subfamilies in which ALDH1A1, ALDH1A3, ALDH3A1, ALDH5A1, ALDH7A1, and ALDH18A1 are implicated in CSC. Existing chemotherapeutic drugs eliminate the bulk of tumors but are usually not effective against CSC which express ALDH+ population. Henceforth, targeting ALDH is convincing to treat the patient's post-relapse.

Scientific Papers found: Click to Expand⟱

1060-

LT,

BTZ,

Luteolin inhibits the TGF-β signaling pathway to overcome bortezomib resistance in multiple myeloma

vitro+vivo,

Melanoma,

ALDH1A1↓, TGF-β↓, ChemoSen↑,

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:

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,

Migration ⓘ

TGF-β↓, 1,

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,
Total Targets: 3

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: ALDH1A1, Aldehyde Dehydrogenase 1A1

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