Luteolin / β-catenin/ZEB1 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.

Luteolin — a naturally occurring polyhydroxylated flavone (3′,4′,5,7-tetrahydroxyflavone) found in celery, parsley, peppers, broccoli and numerous medicinal plants. It is a dietary phytochemical and experimental small-molecule anticancer/anti-inflammatory agent rather than an approved anticancer drug. Standard abbreviation: LUT or Lut. Luteolin occurs as the free aglycone and as plant glycosides; after oral administration, circulating luteolin is dominated by glucuronide and sulfate conjugates rather than free aglycone. Its cancer pharmacology is pleiotropic and strongly model-dependent, with particularly recurrent effects on PI3K/AKT/mTOR, NF-κB, STAT3, redox regulation, mitochondrial apoptosis, EMT/invasion and cell-cycle control.

Primary mechanisms (ranked):

  1. PI3K/AKT/mTOR survival signaling suppression, reducing proliferation and facilitating apoptosis, autophagy or other programmed cell-death responses.
  2. Redox-selective stress modulation: commonly ↑ ROS in susceptible cancer cells together with ↓ NRF2/HO-1/GSH-associated antioxidant defenses, while frequently reducing oxidative stress and activating protective antioxidant systems in normal tissues.
  3. NF-κB and inflammatory survival signaling inhibition, with context-dependent suppression of TNF-α, IL-6, COX-2 and related inflammatory mediators.
  4. Mitochondrial/intrinsic apoptosis activation through ↓ mitochondrial membrane potential, ↑ BAX:BCL-2 ratio, cytochrome-c release and caspase activation.
  5. STAT3/JAK signaling suppression, reducing survival, stemness, inflammatory signaling and immune-evasion phenotypes in several tumor models.
  6. EMT, migration and invasion suppression through modulation of E-cadherin, N-cadherin, vimentin, MMP2/MMP9, FAK, YAP/TAZ and related pathways.
  7. Cell-cycle arrest through suppression of cyclins/CDKs and context-dependent induction of p21/p27 and p53 signaling.
  8. Metabolic and hypoxic adaptation inhibition, including HIF-1α, PKM2, HK2 and glycolytic signaling in selected models.
  9. Epigenetic modulation, including reported inhibition of DNMTs, HDAC-associated signaling and EZH2 in selected cancer models.
  10. Additional context-dependent cell-death mechanisms including ER stress, autophagy, ferroptosis and pyroptosis.

Bioavailability / PK relevance: Oral luteolin has poor aqueous solubility and unfavorable systemic availability of unconjugated aglycone. It is absorbed from the intestine but undergoes extensive intestinal and hepatic glucuronidation and sulfation. Animal studies report low absolute bioavailability of free luteolin, commonly in the low-single-digit to low-tens percentage range depending on formulation and analytical definition. Nanoemulsions, lipid/phospholipid systems, cyclodextrins, nanoparticles and other delivery systems can substantially improve exposure experimentally. Luteolin and particularly some circulating conjugates can interact with OATP1B1/OATP2B1 transporters; in-vitro CYP inhibition has also been reported, making pharmacokinetic drug interactions plausible at sufficiently high exposure.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM luteolin, often 20–50 µM or higher. These concentrations generally exceed sustained concentrations of free luteolin expected after conventional oral dietary or supplemental dosing because extensive conjugation limits circulating aglycone. Consequently, direct translation of many cell-culture IC50 values to standard oral supplementation is weak. Local gastrointestinal exposure, metabolites, tissue deconjugation and optimized formulations may partly alter this limitation.

Clinical evidence status: Predominantly preclinical, but no longer exclusively preclinical. A 2025 single-arm phase I study administered luteolin 50 mg/day for six months to five men with localized prostate cancer undergoing active surveillance; no treatment-related adverse events were reported, but the study was far too small and uncontrolled to establish anticancer efficacy. A larger phase II single-arm multicenter Japanese study of 50 mg/day for one year is currently recruiting with a planned enrollment of 40 patients. Luteolin is therefore best categorized as early-human/phase I–II investigational evidence, not established cancer therapy. Preclinical evidence for chemotherapy and radiotherapy sensitization is substantial but remains cancer-, drug- and genotype-dependent.


-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

-"Additionally, when reacted with concentrated sulfuric acid, a zinc salt is produced, resulting in a dark red and yellow solution. These color changes serve as a strong basis for the identification of luteolin"

Common Dietary and Plant Sources of Luteolin

Source Luteolin Content Approximate Equivalent Relative Source Level Notes
Bird chili 1035 mg/kg 103.5 mg/100 g Very high Highest source in the cited quantitative food table; concentration may vary substantially by cultivar, maturity and analytical method.
Belimbi leaves 464.5 mg/kg 46.45 mg/100 g Very high Leaf material; not a common Western dietary source.
Onion leaves 391 mg/kg 39.1 mg/100 g Very high Green onion/scallion-type leaf tissue can contain substantially more luteolin than onion bulbs.
Belimbi fruit 202 mg/kg 20.2 mg/100 g High Tropical fruit source.
Dried asam gelugur 107.5 mg/kg 10.75 mg/100 g High Dried plant material; dry-weight concentration is not directly comparable with fresh vegetables.
Celery 80.5 mg/kg 8.05 mg/100 g High One of the most commonly cited dietary sources of luteolin; content differs among celery varieties and plant parts.
Broccoli 74.5 mg/kg 7.45 mg/100 g High Common dietary source. Other compositional surveys report a broad range, indicating strong cultivar and methodology effects.
Carrot 37.5 mg/kg 3.75 mg/100 g Moderate Common dietary source; luteolin may occur predominantly in glycosylated forms.
Green chili 33 mg/kg 3.3 mg/100 g Moderate Content varies substantially among Capsicum species and cultivars.
Limau purut leaves 30.5 mg/kg 3.05 mg/100 g Moderate Kaffir lime leaves; primarily used as a culinary herb rather than consumed in large quantities.
French bean 11 mg/kg 1.1 mg/100 g Low to moderate Common food source but substantially lower than celery, broccoli or onion leaves in the cited dataset.
White radish 9 mg/kg 0.9 mg/100 g Low Lower-luteolin dietary source in the cited dataset.
Parsley Approximately 19.75 mg/100 g dried Approximately 197.5 mg/kg dried High Frequently cited as a rich luteolin-containing herb. Dry-weight values should not be compared directly with fresh-weight vegetables.
Thyme Approximately 51 mg/100 g Approximately 510 mg/kg Very high Herb source reported in reviews; intake per serving is usually small despite the high concentration.
Peppermint Approximately 11.33 mg/100 g fresh Approximately 113.3 mg/kg High Fresh peppermint is a relatively concentrated herbal source.
Spinach Approximately 1.11 mg/100 g Approximately 11.1 mg/kg Low to moderate Common dietary source but lower than many herbs and celery-family plants.
Cabbage Approximately 0.4–0.6 mg/100 g Approximately 4–6 mg/kg Low Widely consumed but generally a relatively dilute luteolin source.
Black olives Approximately 3.2–17.5 mg/100 g Approximately 32–175 mg/kg Moderate to high Luteolin concentration depends strongly on olive cultivar and processing.
Green olives Approximately 0.2–1.2 mg/100 g Approximately 2–12 mg/kg Low to moderate Generally reported at lower concentrations than black olives.
Apple peel Variable Not consistently quantified Low to moderate Luteolin is reported principally in the peel rather than the flesh; concentration is cultivar-dependent.
Chrysanthemum flowers Variable Not consistently quantified Potentially high Traditional medicinal/tea source containing luteolin and luteolin glycosides.


Luteolin — Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 PI3K / AKT / mTOR survival signaling ↓ PI3K; ↓ p-AKT; ↓ mTOR ↔ / adaptive modulation R–G ↓ survival and proliferation; ↑ cell death One of the most recurrent anticancer signaling effects; confirmed in multiple tumor systems and newer NSCLC studies.
2 ROS and antioxidant defense ↑ ROS; ↓ SOD/GSH/NRF2/HO-1 (context-dependent) ↓ ROS; ↑ antioxidant defenses (context-dependent) P–R Selective oxidative stress in susceptible tumors Biphasic and highly context-dependent. ROS generation can be mechanistically upstream of NF-κB inhibition, JNK activation, apoptosis and radiosensitization.
3 NRF2 / HO-1 antioxidant survival axis ↓ NRF2; ↓ HO-1 (model-dependent) ↑ NRF2; ↑ HO-1 (model-dependent) R–G ↓ tumor antioxidant capacity and drug resistance Especially relevant in NRF2-high cancer cells. Luteolin has sensitized tumor cells to chemotherapy through NRF2 suppression, whereas NRF2 activation contributes to normal-tissue protection.
4 NF-κB inflammatory survival signaling ↓ NF-κB; ↓ inflammatory survival signaling ↓ pathological NF-κB activation R–G ↑ apoptosis; ↓ inflammation and survival ROS accumulation can participate upstream in some tumor models; not all NF-κB inhibition requires ROS.
5 Mitochondria and intrinsic apoptosis ↓ MMP; ↑ BAX; ↓ BCL-2; ↑ Cyt-c; ↑ caspase-9/3 ↔ / ↓ mitochondrial injury under oxidative-stress conditions R–G ↑ mitochondrial apoptosis A common downstream execution mechanism following AKT inhibition, ROS elevation or ER stress.
6 JAK / STAT3 signaling ↓ STAT3; ↓ p-STAT3 ↔ / ↓ inflammatory STAT3 R–G ↓ proliferation, stemness and immune escape Recent work also links PRDX2 inhibition to JAK2/STAT3 suppression and ↓ PD-L1 in lung adenocarcinoma.
7 EMT and metastatic signaling ↓ EMT; ↑ E-cadherin; ↓ N-cadherin; ↓ vimentin; ↓ MMP2/9 ↔ G ↓ migration, invasion and metastasis PI3K/AKT, TGF-β/Smad, YAP/TAZ, FAK and related axes contribute depending on tumor type.
8 Cell-cycle control ↑ G1 or G2/M arrest; ↓ cyclins/CDKs; ↑ p21/p27 ↔ (model-dependent) G ↓ proliferation Cell-cycle phase varies with tumor lineage and concentration.
9 p53 / JNK apoptotic signaling ↑ JNK; ↑ p53 stability/activity (context-dependent) ↔ R–G ↑ apoptosis and chemotherapy response Cisplatin sensitization can depend strongly on functional p53.
10 Glycolysis and metabolic adaptation ↓ glycolysis; ↓ PKM2; ↓ HK2; ↓ ATP (model-dependent) ↔ G ↓ metabolic support for proliferation Not universal across cancers; strongest evidence comes from selected hepatocellular and other metabolically dependent models.
11 HIF-1α and hypoxic adaptation ↓ HIF-1α; ↓ hypoxic adaptation ↔ G ↓ angiogenesis and hypoxia tolerance Reported in breast, colon and other cancer models; linked to reduced VEGF signaling.
12 VEGF and angiogenesis ↓ VEGF; ↓ VEGFR signaling ↔ / anti-inflammatory vascular effects G ↓ tumor angiogenesis Predominantly preclinical evidence.
13 ER stress and unfolded protein response ↑ PERK/eIF2α/ATF4/CHOP; ↑ ER stress (model-dependent) ↓ pathological ER stress in several injury models R–G ↑ tumor cell death Illustrates luteolin's frequently opposite stress response in malignant versus nonmalignant models.
14 Autophagy ↑ Beclin-1; ↑ LC3-II; ↓ p62 (context-dependent) ↔ / protective modulation G Autophagic stress or contribution to cell death Can be cytotoxic or cytoprotective depending on cancer model and treatment context.
15 GPX4-dependent ferroptosis ↓ GPX4; ↓ GSH; ↑ lipid oxidation; ↑ ferroptosis ↔ / ↓ ferroptotic injury in some normal-tissue models R–G ↑ ferroptotic cancer-cell death Recent colon-cancer work supports GPX4-linked ferroptosis plus enhanced antitumor immune activation.
16 Epigenetic regulation ↓ DNMT activity; ↓ HDAC-associated signaling; ↓ EZH2 (model-dependent) ↔ / context-dependent G Re-expression of growth-suppressive programs Mechanistically interesting but less broadly established than AKT, redox and inflammatory pathways.
17 YAP / Wnt and tumor immunity ↓ YAP; ↓ Wnt-associated signaling; ↓ immune escape ↑ CTL functional activity indirectly G ↑ antitumor T-cell effectiveness 2025 animal work suggests luteolin can enhance tumor-specific CTL therapy; clinical relevance remains unproven.
18 Chemosensitization ↑ response to cisplatin and several other agents (drug-dependent) Variable; possible tissue protection in other contexts G ↓ treatment resistance Mechanisms include ↓ NRF2, ↓ AKT, ↑ p53/JNK, mitochondrial apoptosis and suppression of resistance pathways. Evidence remains predominantly preclinical.
19 Radiosensitization ↑ radiation-induced ROS and apoptosis Potential radioprotection reported in nonmalignant models R–G ↑ radiation response In NSCLC models, p38/ROS/caspase signaling increased radiosensitivity; tumor versus normal-tissue effects require careful context separation.
20 Clinical Translation Constraint High in-vitro concentrations often required Systemic exposure dominated by conjugated metabolites G Limits translation of cell-culture potency Poor aqueous solubility, extensive phase-II metabolism, formulation dependence, possible transporter/drug interactions and extremely limited controlled human oncology evidence remain major constraints.

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



Luteolin — Alzheimer’s disease relevance: Luteolin has substantial preclinical neuroprotective evidence and is sufficiently relevant to Alzheimer’s disease to warrant a separate database section. Reported effects include ↓ amyloid-β production/accumulation, ↓ BACE1-associated amyloidogenic processing, ↓ tau hyperphosphorylation, ↓ neuroinflammation, ↓ oxidative stress, ↓ NLRP3/NF-κB signaling and ↑ BDNF/TrkB-associated neuroplasticity. Acetylcholinesterase inhibition has also been reported. However, evidence remains predominantly cellular and animal; convincing disease-modifying clinical evidence in Alzheimer’s disease is absent. Oral bioavailability and blood-brain exposure of free luteolin remain important translational constraints.

Clinical evidence status: Preclinical. Contemporary reviews identify Alzheimer’s disease as the neurodegenerative disorder in which luteolin has been studied most extensively, but explicitly note that clinical therapeutic evidence remains deficient.

Luteolin — Alzheimer’s Disease Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Neuroinflammation / NF-κB ↓ NF-κB; ↓ IL-1β; ↓ IL-6; ↓ TNF-α ↓ chronic neuroinflammation Among the most consistently proposed neuroprotective actions.
2 Amyloid-β pathology ↓ Aβ; ↓ Aβ42 ↓ amyloid burden Supported predominantly by cellular and animal studies.
3 BACE1 / amyloidogenic processing ↓ BACE1 ↓ amyloidogenic APP processing Potential upstream mechanism contributing to reduced Aβ generation.
4 Tau phosphorylation ↓ p-tau ↓ tau pathology Multiple preclinical models report reduced abnormal tau phosphorylation.
5 Oxidative stress / NRF2 ↓ ROS; ↑ NRF2; ↑ antioxidant defenses ↓ neuronal oxidative injury Direction differs from the pro-oxidant effect frequently exploited in cancer cells.
6 NLRP3 inflammasome ↓ NLRP3 ↓ inflammasome-driven neuronal inflammation Potential bridge between redox stress and neuroinflammation.
7 BDNF / TrkB neuroplasticity ↑ BDNF; ↑ TrkB ↑ synaptic and neuronal support Observed in several neurobehavioral models.
8 Acetylcholinesterase ↓ AChE ↑ cholinergic signaling Primarily biochemical/preclinical evidence; clinical magnitude is unknown.
9 Neuronal apoptosis and mitochondrial stress ↓ apoptosis; ↓ mitochondrial injury ↑ neuronal survival Opposite phenotypic direction from luteolin-induced apoptosis in many cancer models.
10 Clinical Translation Constraint Low free-luteolin exposure; limited human CNS data Uncertain clinical efficacy Human Alzheimer’s disease efficacy trials are insufficient; brain exposure and formulation remain unresolved.


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
8378- LT,    Luteolin and its derivatives: modulation of epithelial-mesenchymal transition in fibrosis and cancer
- Review, Var, NA
EMT↓, Luteolin inhibits EMT via multi-target regulation of core pathways (TGF-β1/Smad, PI3K/Akt, Hippo/YAP), exerting consistent dose-dependent efficacy in suppressing cancer metastasis
TGF-β1↓, downregulates TGF-β1
Smad1↓,
PI3K↓, uteolin not only suppresses downstream Smad-dependent transcriptional responses but also attenuates key non-Smad signaling branches, including PI3K/Akt and MAPK pathways
Akt↓,
Hippo↝,
YAP/TEAD↓, This effectively suppresses YAP/TAZ-driven transcriptional programs that are activated by mechanical stress and growth factors,
*NRF2↑, luteolin could alleviate the pathological process driven by oxidative stress by activating the Nrf2/HO-1 antioxidant pathway, regulating AMPK energy sensing and inhibiting NADPH oxidase-derived reactive oxygen species
*HO-1↑,
*ROS↓,
E-cadherin↑, restores E-cadherin/ZO-1 (epithelial markers); suppresses N-cadherin, Vimentin, Claudin-1, β-catenin, Snail, TCF/ZEB1 (mesenchymal markers)
ZO-1↑,
Vim↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
TCF↓,
Zeb1↓,
angioG↓, 4. Inhibits angiogenesis,
eff↑, luteolin and its derivative apigenin enhance antitumor immunity in KRAS-mutant lung cancer by suppressing STAT3-mediated PD-L1 expression, thereby synergizing with PD-1 blockade
ROS↑, pca: Oxidative stress and apoptosis in mCRPC cells; cytotoxicity and pro-oxidant effects
mtDam↑, In gastric cancer, luteolin inhibits tumor progression primarily by inducing mitochondrial dysfunction and triggering the intrinsic apoptotic pathway—evidenced by loss of mitochondrial membrane potential and impaired electron transport chain activi
MMP↓,
ETC↓,

8397- LT,    Effects and Mechanisms of Luteolin, a Plant-Based Flavonoid, in the Prevention of Cancers via Modulation of Inflammation and Cell Signaling Molecules
- Review, Var, NA
tumCV↓, The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/β-catenin, and cell-cycle arrest, and induce apoptosis.
TumCP↓,
angioG↓,
TumCI↓,
TumMeta↓,
mTOR↓,
PI3K↓,
Akt↓,
STAT3↓,
Wnt↓,
β-catenin/ZEB1↓,
TumCCA↑,
Apoptosis↑,
hTERT/TERT↓, after 24 h of treatment with luteolin at concentrations of 10 and 30 µM, the mRNA expression levels of hTERT were significantly downregulated
AP-1↓, down-regulation of nuclear AP-1 and NF-κB and the inhibition of the MAPK signaling pathway.
NF-kB↓,
MAPK↓,
HSP90↓, luteolin was observed to reduce the association between the androgen receptor and heat-shock protein 90, ultimately leading to AR degradation
AR↓,
IGF-1R↓, luteolin inhibited IGF-1R/AKT signaling
Akt↓,
NOTCH↓, Luteolin may inhibit Notch signaling by regulating miRNAs.
IL6↓, inhibiting the IL-6/STAT3 signaling pathway
MMP2↓, luteolin was found to visibly downregulate the expressions of MMP-2, MMP-3, MMP-9, and MMP-16.
MMP3↓,
MMP9↓,
MMP16↓,
TumVol∅, consumption of luteolin did not appear to affect tumor growth in vivo, as no significant differences were observed in tumor volume or weight
TumW∅,
miR-34a↑, BGC-823 and SGC-7901 Upregulation of miR-34a
miR-107↑, MKN45 or BGC823 Upregulated miR-107, miR-34a and miR-139
miR-139-5p↑,
miR-422a↑, MKN45 or BGC823 Upregulated miR-34a and miR-422a
miR-21↓, MKN45 or BGC823 Downregulated miR-21, miR-155
miR-155↓,
miR-224↓, MKN45 or BGC823 Downregulated miR-224, miR-340
miR-340↓,
*toxicity↓, 100 mg/kg of luteolin did not cause any liver or kidney toxicity, which indicates a favorable safety profile for luteolin

8392- LT,    Revisiting Luteolin Against the Mediators of Human Metastatic Colorectal Carcinoma: A Biomolecular Approach
- in-vitro, CRC, HCT15 - in-vitro, CRC, HCT116 - in-vitro, CRC, DLD1 - in-vitro, CRC, HT-29 - in-vitro, Nor, RWPE-1
selectivity↑, luteolin was found to be effective against the different mCRC cell lines (HCT-15, HCT-116, DLD-1, and HT-29) without hampering the viability of non-tumorigenic ones (RWPE-1).
β-catenin/ZEB1↓, luteolin was found to inhibit β-catenin activity (a key regulator of mCRC) through direct physical interactions
GSK‐3β↑, by activating GSK3-β and ceasing its activation by inactivating AKT1 and PI3K-α.
AKT1↓,
PI3K↓,
p50↓, Luteolin also inhibited p50 activity, which could be useful in mitigating mCRC-associated proinflammatory milieu.

8384- LT,    Current situation and research progress of luteolin in the treatment of gastrointestinal malignant tumors
- Review, GC, NA
Apoptosis↑, inducing tumor cell apoptosis, promoting autophagy, arresting the cell cycle, inhibiting epithelial-mesenchymal transition (EMT), enhancing tumor cell peroxidation,
TumAuto↑,
TumCCA↑,
EMT↓,
*ROS↓, luteolin to modulate the activity of reactive oxygen species (ROS) scavenging enzymes, act as an antioxidant, regulate pro-inflammatory factors,
*antiOx↑,
ROS↑, Intriguingly, luteolin can also exhibit pro-oxidative effects and demonstrate anticancer properties under specific circumstances
P53↑, luteolin activates the p53 signaling pathway, leading to apoptosis and cell cycle arrest in CRC
LC3II↑, luteolin increases levels of LC3-II and Beclin 1 proteins in a p53-dependent manner
Beclin-1/ATG6↑,
p‑MAP2K1/MEK1↓, luteolin reduces the expression of p-MEK 1 and p-ERK 1/2 in CRC cells in a dose-dependent manner.
p‑ERK↓,
BAX↑, followed by upregulation of apoptosis-related proteins BAX and cleaved Caspase-3, and downregulation of Bcl-2.
cl‑Casp3↑,
Bcl-2↓,
p‑MAPK↓, CRC cells by inhibiting phosphorylation of the MAPK pathway.
DNArepair↓, luteolin downregulates DNA repair proteins, such as HMGB1, LIG, and XRCC1, while upregulating ERCC-3, resulting in DNA single-strand breaks and ultimately apoptosis.
HMGB1↓,
XRCC1↓,
ERCC3↑,
CycB/CCNB1↓, research reveals that luteolin treatment decreases levels of G2-M phase-related proteins Cyclin B1 and CDC2, while increasing p-CHK1 in a concentration-dependent manner.
CDC2↓,
p‑CHK1↑,
TumCCA↑, This indicates that luteolin can induce G2/M phase arrest in CRC cells, thereby inhibiting CRC cell proliferation
TumCP?,
Wnt↓, luteolin dose-dependently suppressed the expression of Wnt3 and β-catenin in CRC cells.
β-catenin/ZEB1↓,
miR-384↑, inhibition of PTN expression by luteolin through upregulation of miR-384.
PTN↓,
MMP2↓, The decrease of PTN expression finally inhibited the expression of matrix metalloproteinases MMP-2, MMP-3, MMP-9 and MMP-16 related to tumor migration
MMP3↓,
MMP9↓,
MMP16↓,
Ferroptosis↑, Ferroptosis is also one of the most important ways that luteolin exerts its anti-CRC effect.
GPx4↓, luteolin further reduced the expression of tumor survival-related protein GPX4 by up-regulating the expression of HIC1 in CRC cells
Synergy↑, luteolin significantly reduced tumor mass and volume by combining with Erastin, and significantly down-regulated the expression of Ki67 and GSH in tumor tissues.
Ki-67↓,
GSH↓,
ChemoSen↑, luteolin is used in combination with some chemotherapeutic drugs, luteolin can mediate multiple pathways such as cell apoptosis, autophagy, and inhibition of angiogenesis, improving the sensitivity of CRC cells to chemotherapeutic drugs.
TumCP↓, Luteolin can inhibit the proliferation, migration, invasion and drug resistance of GC cells by inhibiting PI3K/AKT/mTOR, NF-κB, Notch, MAPK and other classical pathways.
TumCMig↓,
TumCI↓,
PI3K↓,
Akt↓,
mTOR↓,
NF-kB↓,
NOTCH↓,
miR-139-5p↑, promoting the expression of tumor suppressor miR-139, miR-34a, miR-422a and miR-107, inhibiting the expression of tumor promoter miR-21, miR-155, miR-224 and miR-340,
miR-34a↑,
miR-422a↑,
miR-107↑,
miR-21↓,
miR-155↓,
miR-224↓,
miR-340↓,
E-cadherin↑, promoting the expression of E-cadherin by inhibiting tumor migration-related proteins MMP2, MMP9, N-cadherin and vimentin.
N-cadherin↓,
Vim↓,
HK1↓, inhibiting the expression of HK1, p-MAPK and p-ERK, promoting the expression of P53 and P21, inducing G1 phase arrest of GC cells
FOXO1↓, inhibit GC cells by up-regulating FOXO1 expression
compI↓, inhibit the activity of METC Complexes I, III and V at the same time, destroy mitochondrial outer membrane by down -regulating Bcl-2 and up-regulating Bax protein, and then induce apoptosis
compIII↓,
compV↓,
ETC↓,
BioAv↝, Due to the poor water solubility and low bioavailability of luteolin, Karole et al. studied to improve the bioavailability of luteolin in order to enhance the therapeutic effect by non-invasively overcoming the intestinal epithelial barrier through l

1171- LT,    The inhibition of β-catenin activity by luteolin isolated from Paulownia flowers leads to growth arrest and apoptosis in cholangiocarcinoma
- in-vitro, CCA, NA
Wnt↓,
TumCCA↑, G2/M phase
Apoptosis↑,
TumCMig↓,
β-catenin/ZEB1↓, inhibitor of β-catenin
cMyc↓,
cycD1/CCND1↓,

2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
ChemoSen↑,
chemoP↑,
*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
*Catalase↑,
*SOD↑,
*GPx↑,
*GSTs↑,
*GSH↑,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*IL10↑,
NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
HO-1↓,
NQO1↓,
GSH↓,
MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
p‑MET↓,
p‑Akt↓,
HGF/c-Met↓,
NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
Bcl-2↓,
SOD2↓,
Casp8↑,
Casp3↑,
PARP↑,
MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
NLRP3↓,
ASC↓,
Casp1↓,
IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
IKKα↓,
p‑p65↓,
p‑p38↑,
MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
ICAM-1↓,
EGFR↑,
p‑PI3K↓,
E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
ZO-1↑,
N-cadherin↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
Vim↑,
ITGB1↓,
FAK↓,
p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
Rac1↓,
Cdc42↓,
Rho↓,
PCNA↓, Lung cancer model ↓Cyclin B1, ↑p21, ↑p-Cdc2, ↓Vimentin, ↓MMP9, ↑E-cadherin, ↓AIM2, ↓Pro-caspase-1, ↓Caspase-1 p10, ↓Pro-IL-1β, ↓IL-1β, ↓PCNA
Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
AXL↓,
CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
NSE↓,
SOD↓,
Catalase↓,
GPx↓,
GSR↓,
GSTs↓,
GSH↓,
VitE↓,
VitC↓,
CYP1A1↓,
cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
AR↓, ↓Androgen receptor
AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
VEGF↓,
H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
H4↓,
HDAC↓,
SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
Cyt‑c↑,
p‑JNK↑,
PTEN↓, Lung cancer model 1/5/10/30/50/80/100 μmol/L ↑Cleaved caspase-3, ↑PARP, ↑Bax, ↓Bcl-2, ↓EGFR, ↓PI3K/Akt/PTEN/mTOR, ↓CD34, ↓PCNA
mTOR↓,
CD34↓,
FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
Fas↑,
XIAP↓,
p‑eIF2α↑,
CHOP/DDIT3↑,
LC3II↑,
PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
STAT3↓,
IL2↑,
EMT↓, Luteolin exerts anticancer activity by inhibiting EMT, and the possible mechanisms include the inhibition of the EGFR-PI3K-AKT and integrin β1-FAK/Src signaling pathways
cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
*Half-Life↝, ats administered an intraperitoneal injection of luteolin (60 mg/kg) absorbed it rapidly as well, with peak levels reached at 0.083 h (71.99 ± 11.04 μg/mL) and a prolonged half-life (3.2 ± 0.7 h)
*eff↑, Luteolin chitosan-encapsulated nano-emulsions increase trans-nasal mucosal permeation nearly 6-fold, drug half-life 10-fold, and biodistribution of luteolin in brain tissue 4.4-fold after nasal administration


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GPx↓, 1,   GPx4↓, 1,   GSH↓, 3,   GSR↓, 1,   GSTs↓, 1,   HO-1↓, 1,   NQO1↓, 1,   NRF2↓, 1,   ROS↑, 3,   SOD↓, 1,   SOD2↓, 1,   VitC↓, 1,   VitE↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

CDC2↓, 1,   compI↓, 1,   compIII↓, 1,   compV↓, 1,   ETC↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

GSK‐3β↑, 1,   HK1↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   Apoptosis↑, 3,   ASC↓, 1,   BAX↑, 1,   Bcl-2↓, 2,   Casp1↓, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   FasL↑, 1,   Ferroptosis↑, 1,   p‑MDM2↓, 1,   p‑p38↑, 1,   XIAP↓, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 4,   p‑Akt↓, 1,   AKT1↓, 1,   EGFR↑, 1,   p‑ERK↓, 1,   HGF/c-Met↓, 1,   Hippo↝, 1,   IGF-1R↓, 1,   IKKα↓, 1,   p‑JNK↑, 1,   p‑MAP2K1/MEK1↓, 1,   MAPK↓, 2,   p‑MAPK↓, 1,   mTOR↓, 3,   PI3K↓, 4,   p‑PI3K↓, 1,   PTEN↓, 1,   p‑Src↓, 1,   STAT3↓, 2,   p‑STAT6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 1,   FOXO1↓, 1,   H3↓, 1,   H4↓, 1,   HDAC↓, 1,   miR-107↑, 2,   miR-139-5p↑, 2,   miR-155↓, 2,   miR-21↓, 2,   miR-224↓, 2,   miR-340↓, 2,   miR-34a↑, 2,   miR-384↑, 1,   miR-422a↑, 2,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   p‑eIF2α↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↑, 1,   LC3II↑, 2,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNArepair↓, 1,   ERCC3↑, 1,   hTERT/TERT↓, 1,   P53↑, 1,   PARP↑, 1,   PCNA↓, 1,   XRCC1↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

p‑CHK1↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   Ki-67↓, 1,   TumCCA↑, 4,  

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

CD34↓, 1,   cFos↑, 1,   Ki-67↓, 1,   NOTCH↓, 2,   NOTCH1↓, 1,   TumCP?, 1,   TumCP↓, 2,   Wnt↓, 3,  

Migration(tgid=13) ⓘ

AP-1↓, 1,   AXL↓, 1,   Cdc42↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   EMT↓, 3,   FAK↓, 1,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP16↓, 2,   MMP2↓, 3,   MMP3↓, 2,   MMP9↓, 2,   N-cadherin↓, 2,   Rac1↓, 1,   Rho↓, 1,   Smad1↓, 1,   Snail↓, 2,   TGF-β1↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumMeta↓, 1,   Tyro3↓, 1,   Vim↓, 2,   Vim↑, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 6,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 2,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

CLDN1↓, 2,   MMP↓, 1,   ZO-1↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

HMGB1↓, 1,   ICAM-1↓, 1,   IL2↑, 1,   IL6↓, 2,   NF-kB↓, 3,   NLRP3↓, 1,   p50↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   TCF↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

PTN↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 2,   CYP1A1↓, 1,   eff↑, 1,   RadioS↑, 1,   selectivity↑, 1,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 2,   CEA↓, 1,   EGFR↑, 1,   hTERT/TERT↓, 1,   IL6↓, 2,   NSE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cachexia↓, 1,   chemoP↑, 1,   TumVol∅, 1,   TumW∅, 1,  
Total Targets: 165

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   SOD↑, 1,  

Cell Death(tgid=5) ⓘ

Casp3↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL10↑, 1,   IL1β↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,   Half-Life↝, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,  
Total Targets: 17

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
6 Luteolin
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#:118  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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