Luteolin / HO-1 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.


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
*lipid-P↓, Baicalein and luteolin prevented the Fe-SP-induced lipid peroxidation in rat neonatal cardiomyocytes.
*ACSL4∅, Baicalein and luteolin can reduce the protein levels of ACSL4 and Nrf2, and enhance the protein levels of GPX4 in ischemia/reperfusion-treated rat hearts.
*NRF2∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein
*GPx4∅, BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein, and the I/R-decreased GPX4 protein levels
*Ferroptosis↓, BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation.
*ROS↓,
*MDA↓, Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers
*eff↑, BAI and Lut reduced the I/R-induced myocardium infarction
*HO-1∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein

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↓,

8369- LT,    Luteolin inhibits proliferation of lung cancer A549 cells by increasing ROS production and inhibiting the AKT/mTOR signaling pathway and HO-1 expression
- in-vitro, Lung, A549
tumCV↓, luteolin dose-dependently inhibited the viability and proliferation of A549 cells, increased intracellular ROS levels, up-regulated the expressions of Bax, cleaved caspase-9, and Beclin 1
TumCP↓,
ROS↑,
BAX↑,
cl‑Casp9↑,
Beclin-1/ATG6↑,
LC3B-II↑, increased the LC3B-II/LC3B-I ratio, down-regulated the expressions of Bcl-2 and P62, and induced cell apoptosis and autophagy.
Bcl-2↓,
p62↓,
TumAuto↑,
p‑Akt↓, Luteolin also significantly inhibited the phosphorylation of AKT and mTOR and down-regulated the expression of HO-1 protein in the cells.
p‑mTOR↓,
HO-1↓,

8401- LT,    Multi-Faceted Role of Luteolin in Cancer Metastasis: EMT, Angiogenesis, ECM Degradation and Apoptosis
- Review, Var, NA
EMT↓, The flavone interferes with the epithelial-mesenchymal transition (EMT) by inhibiting the expression of N-cadherin, vimentin
N-cadherin↓,
Vim↓,
VEGF↓, mainly by blocking the VEGF/VEGFRs signaling pathway and by inhibiting MMPs.
VEGFR1↓,
MMPs↓,
Telomerase↓, Reduction of telomerase expression by targeting NF-κB/c-Myc; increase of Bax/Bcl-2 ratio and caspase-3
NF-kB↓,
cMyc↓,
Bax:Bcl2↑,
Casp3↑,
PI3K↓, Repression of PI3K/Akt pathway; induction of FOXO3a expression and increase of p21 and p27; induction of PARP cleavage and release of cytochrome c
Akt↓,
FOXO3↑,
P21↑,
p27/CDKN1B↑,
cl‑PARP↑,
Cyt‑c↑,
NOTCH↓, Repression of Notch signaling and its downstream targets Notch-1, Hes-1, VEGF
HES1↓,
ROS↑, Induction of ROS accumulation via suppression of SOD activity;
SOD↓,
miR-34b-5p↑, Upregulation of miR-34a-5p
Hif1a↓, inhibition of HIF-1α/VEGF axis
P21↓, downregulation of p21, survivin, Mcl-1, Bcl-x(L) and Mdm-2
survivin↓,
Mcl-1?,
Bcl-xL↓,
MDM2↓,
MMP2↓, Downregulation of MMP-2, -9, -3 and -16 expression coupled with an enhancement of miR-384
MMP9↓,
MMP3↓,
MMP16↓,
miR-384↑,
NRF2↓, Inhibition of Nrf2
HO-1↓, downregulation of the antioxidant genes γ-glutamylcysteine ligase and heme oxygenase-1,
angioG↓, Luteolin Suppresses Angiogenesis

8394- LT,    Luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation
- in-vitro, Nor, NA
*Pyro↓, The results showed that luteolin exhibited a potent preventive effect on THP-1 macrophage pyroptosis
*NLRP3↓, luteolin was found to significantly reduce the expression of NLRP3, pro-CASP-1 and CASP-1,
*proCasp1↓,
*Casp1↓,
*NRF2↑, luteolin promoted Nrf2 nuclear translocation, thereby increasing the expression of HO-1 that reduces ROS production,
*HO-1↑,
*ROS↓,

8390- LT,    Luteolin in Inflammatory Bowel Disease and Colorectal Cancer: A Disease Continuum Perspective
- Review, IBD, NA - Review, CRC, NA
*Diff↝, luteolin regulates immune cell differentiation, mitigates inflammation and oxidative stress, modulates gut microbiota, and restores intestinal mucosal barrier function in IBD.
*Inflam↓,
*ROS↓, Reduction in the Inflammatory Response and Reactive Oxygen Species (ROS)
*GutMicro↑,
*IBI↑,
TumCP↓, In the context of CRC, luteolin demonstrates significant anti-tumor effects by inhibiting cancer cell proliferation, inducing apoptosis, and suppressing cell migration and invasion.
Apoptosis↑,
TumCMig↓,
TumCI↓,
*BioAv↑, such as the use of polymer micelles and responsive nanoparticles, have greatly improved the bioavailability and efficacy of luteolin.
*iNOS↓, It effectively mitigates the inflammatory response by decreasing the expression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6).
*TNF-α↓,
*IL6↓,
*MDA↓, luteolin lowered colonic dialdehyde (MDA) levels, a biomarker of lipid peroxidation, indicating its antioxidant effects
*lipid-P↓,
*antiOx↑,
*NRF2↑, The antioxidant properties of luteolin are associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
*HO-1↑, This pathway activation enhances the expression of antioxidant enzymes, including heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1), which are crucial for maintaining intracellular redox balance
*NQO1↑,
*SOD↑, Luteolin treatment also increased the activities of colonic superoxide dismutase (SOD) and catalase (CAT), key components of the cellular antioxidant defense system that help mitigate oxidative stress damage
*Catalase↑,
*5HT↓, Luteolin reduced the generation of 5-HT by inhibiting TPH-1 expression and the MAPK/ERK signaling pathway, thus producing an inhibitory effect on intestinal inflammation
*TPH1↓,
*MAPK↓,
*ERK↓,
*Inflam↓,
cycD1/CCND1↓, luteolin downregulates the expression of Cyclin D1 and CDK4, blocking the transition of CRC cells from the G1 phase to the S phase, thereby reducing cell proliferation
CDK4↓,
TumCCA↑,
Casp3↑, luteolin activates Caspase-3 and Caspase-9, triggering the mitochondrial pathway to promote cell death.
Casp9↑,
PI3K↓, luteolin inhibits the activation of the PI3K/Akt signaling pathway, reducing the phosphorylation of Akt and mTOR, thus inhibiting CRC cell survival
Akt↓,
p‑Akt↓,
p‑mTOR↓,
E-cadherin↑, enhancement of E-cadherin levels while simultaneously reducing N-cadherin and Vimentin
N-cadherin↓,
Vim↓,

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE/β-secretase↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*Synergy↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

2907- LT,    Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems
- in-vitro, Nor, NA
*ROS↓, Intracellular ROS levels and damage to cellular components such as lipids and DNA in H2O2-treated cells were significantly decreased by luteolin pretreatment.
*Casp9↓, Luteolin suppressed active caspase-9 and caspase-3 levels while increasing Bcl-2 expression and decreasing Bax protein levels.
*Casp3↓,
*Bcl-2↑,
*BAX↓,
*GSH↑, luteolin restored levels of glutathione that was reduced in response to H2O2.
*SOD↑, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1.
*Catalase↑,
*GPx↑,
*HO-1↑,
*antiOx↑, upregulating antioxidant enzymes.
*lipid-P↓, protective effect of luteolin against lipid peroxidation
*p‑γH2AX↓, showed that luteolin pretreatment diminished expression levels of phospho-H2A.X in H2O2-exposed cells
eff↑, promising therapeutic agent for management and treatment of conditions such as COPD and pulmonary fibrosis.

2589- LT,  Chemo,    Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
- in-vitro, BC, MDA-MB-231
NRF2↓, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features
HO-1↓,
ChemoSen↑, combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells.
CSCs↓, Luteolin Inhibited Cancer Stemness Capacity in MDA-MB-231 Cells
SIRT1↓, luteolin suppressed Nrf2, HO-1, Sirt3, and Cripto-1 expression in MDA-MB-231 cells.

2588- LT,  Chemo,    Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway
- in-vitro, CRC, HCT116
NRF2↓, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner.
NQO1↓, Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells.
HO-1↓,
GSH↓,
ChemoSen↑, uteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect.

2587- LT,    Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs
- in-vitro, Lung, A549
NRF2↓, luteolin elicited a dramatic reduction in Nrf2 at both the mRNA and the protein levels, leading to decreased Nrf2 binding to AREs, down-regulation of ARE-driven genes, and depletion of reduced glutathione.
GSH↓,
ChemoSen↑, luteolin significantly sensitized A549 cells to the anticancer drugs oxaliplatin, bleomycin, and doxorubicin.
HO-1↓, ↓HO-1

2921- LT,    Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies
- Review, Nor, NA
*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1/SREBF1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1/ATG6↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP/DDIT3↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

2927- LT,    Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells
- in-vitro, Cerv, HeLa
TumCMig↓, luteolin inhibited migration and colony formation in HeLa cells.
DNMTs↓, Luteolin decreased DNMT activity in HeLa cells in a concentration-dependent manner.
HDAC↓, Luteolin Decreases HDAC Activity in HeLa Cells
HATs↓, Luteolin Reduces the HAT Activity in a Dose-Dependent Manner
ac‑H3↓, H3 acetylation marks were diminished after treatment with the 20 µM of luteolin
ac‑H4↓, the acetylation marks at H4 were also modulated,
MMP2↓, Luteolin resulted in downregulation of expression of various proteins related to migration and inflammation in HeLa cells, and fold changes (FC) after treatment with 10 and 20 µM for 48 h are given, respectively, for MMP2 (FC 0.33, 0.26), MMP3 (FC 0.
MMP9↓,
HO-1↓, Genes related to cell proliferation, growth, and apoptosis such as BCL-X (FC 0.55, 0.45), HO-1/HMOX1 (FC 0.40, 0.25), Kallikrein6 (FC 0.55, 0.48), Kallikrein 3/PSA (FC 0.58, 0.48) were reduced.
E-cadherin↑, E-cadherin (FC 1.8, 2.9) were upregulated
EZH2↓, Luteolin has depicted increased expression of MiR-26a, which is a regulator of EZH2, and at the same time, it has inhibited EZH2
HER2/EBBR2↓, luteolin treatment decreased the inflammatory and migratory proteins such as MMp-2, MMP-3, HO-1/HMOX1, Her1, HER2, Her4, mesothelin, cathepsin B, MUC1, nectin 4, FOXC2, IL-18 BPa, CCL3/MIP-1α, CXCL8/IL-8, IL-2
IL18↓,
IL8↓,
IL2↓,

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

2915- LT,    Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells
- in-vitro, Colon, HT29 - in-vitro, CRC, SNU-407 - in-vitro, Nor, FHC
DNMTs↓, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases,
TET1↑,
NRF2↑, luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2
HDAC↓, Recently, Zao et al. demonstrated that luteolin epigenetically activates the Nrf2 pathway by downregulating DNA methyltransferase (DNMT) and histone deacetylase (HDAC) expression
tumCV↓, Luteolin decreased the viability of all three cell lines in a dose-dependent manner
BAX↑, luteolin upregulated the expression of the apoptotic protein Bax, active caspase-9, and active caspase-3, while it downregulated the expression of the anti-apoptotic protein Bcl-2,
Casp9↑,
Casp3↑,
Bcl-2↓,
ROS↓, Luteolin promotes ROS scavenging by inducing the expression of antioxidant enzymes
GSS↑, luteolin increased the protein expression of the antioxidant enzymes GCLc, GSS, catalase, and HO-1 in a dose- and time-dependent manner
Catalase↑,
HO-1↑,
DNMT1↓, Luteolin markedly decreased the protein expression of DNMT1, DNMT3A, and DNMT3B in a dose- and time-dependent manner
DNMT3A↓,
TET1↑, In contrast, it markedly increased the protein expression of TET1, TET2, and TET3 in a dose- and time-dependent manner
TET3↑,
TET2↓,
P53↑, Luteolin upregulated the expression of p53 and its target p21 in a dose- and time-dependent manner
P21↑,

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
CXCR4↓,
PI3K↓,
Akt↓,
ERK↓,
TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
LC3B-II↑,
EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
E-cadherin↑,
N-cadherin↓,
Wnt↓,
ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
iNOS↓, Luteolin in colon cancer and the complications associated with it, particularly the decreasing effect on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
COX2/PTGS2↓,
NRF2↑, Luteolin has been identified to increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial transcription factor with anticarcinogenic properties related
Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
ChemoSen↓, high dose of Luteolin application negatively affected the oxaliplatin-based chemotherapy in a p53-dependent manner [52]. They suggested that the flavonoids with Nrf2-activating ability might interfere with the chemotherapeutic efficacy of anticancer
IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
AR↓, downregulating the androgen receptor (AR) expression
TIMP1↑, Luteolin inhibits the migration of U251MG and U87MG human glioblastoma cell lines by downregulating MMP-2 and MMP-9 and upregulating the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2.
TIMP2↑,
ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
CDK2↓, Luteolin’s ability to decrease Akt, polo-like kinase 1 (PLK1), cyclin B1, cyclin A, CDC2, cyclin-dependent kinase 2 (CDK2) and Bcl-xL
Telomerase↓, Luteolin dose-dependently inhibited the telomerase levels and caused the phosphorylation of NF-κB and the target gene of NF-κB, c-Myc to suppress the human telomerase reverse transcriptase (hTERT)
p‑NF-kB↑,
p‑cMyc↑,
hTERT/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
MDR1↓,


Showing Research Papers: 1 to 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   Catalase↑, 1,   GPx↓, 1,   GSH↓, 4,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 1,   HO-1↓, 8,   HO-1↑, 1,   NQO1↓, 2,   NRF2↓, 6,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 5,   SOD↓, 2,   SOD2↓, 1,   VitC↓, 1,   VitE↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

CDC2↓, 1,   ETC↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

p‑GSK‐3β↓, 1,   SIRT1↓, 2,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   Apoptosis↑, 1,   ASC↓, 1,   BAX↑, 4,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp3↑, 4,   cl‑Casp3↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 2,   Cyt‑c↑, 2,   DR5↑, 2,   Fas↑, 2,   FasL↑, 1,   iNOS↓, 1,   Mcl-1?, 1,   MDM2↓, 2,   p‑MDM2↓, 1,   p‑p38↑, 1,   survivin↓, 2,   XIAP↓, 2,   YAP/TEAD↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 4,   p‑Akt↓, 3,   EGFR↑, 1,   ERK↓, 1,   HER2/EBBR2↓, 1,   HGF/c-Met↓, 1,   Hippo↝, 1,   IKKα↓, 1,   JNK↑, 1,   p‑JNK↑, 1,   MAPK↓, 1,   mTOR↓, 1,   p‑mTOR↓, 2,   PI3K↓, 4,   p‑PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 2,   p‑STAT6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 1,   p‑cMyc↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 2,   EZH2↓, 1,   FOXO3↑, 1,   H3↓, 1,   ac‑H3↓, 1,   H4↓, 1,   ac‑H4↓, 1,   HATs↓, 1,   HDAC↓, 3,   HES1↓, 1,   miR-34b-5p↑, 1,   miR-384↑, 1,   TET3↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↑, 2,   LC3B-II↑, 2,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   hTERT/TERT↓, 1,   P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   Telomerase↓, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   P21↓, 1,   P21↑, 3,   p27/CDKN1B↑, 1,   TumCCA↑, 1,  

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

CD34↓, 1,   cFos↑, 1,   CSCs↓, 1,   NICD↓, 1,   NOTCH↓, 1,   NOTCH1↓, 2,   TAZ↓, 1,   TumCP↓, 3,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

AEG1↓, 1,   AXL↓, 1,   Ca+2↑, 1,   Cdc42↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 4,   EMT↓, 4,   FAK↓, 1,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP16↓, 1,   MMP2↓, 4,   MMP3↓, 1,   MMP9↓, 3,   MMPs↓, 1,   N-cadherin↓, 4,   Rac1↓, 1,   Rho↓, 1,   Smad1↓, 1,   Snail↓, 2,   TET1↑, 2,   TGF-β1↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 1,   TumCMig↓, 2,   Tyro3↓, 1,   Vim↓, 3,   Vim↑, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 3,   Hif1a↓, 1,   VEGF↓, 3,   VEGFR1↓, 1,   VEGFR2/KDR/Flk1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

CLDN1↓, 2,   MMP↓, 1,   ZO-1↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IL18↓, 1,   IL2↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 4,   p‑NF-kB↑, 1,   NLRP3↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   TCF↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 5,   CYP1A1↓, 1,   eff↑, 2,   MDR1↓, 1,   RadioS↑, 2,   TET2↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 2,   CEA↓, 1,   EGFR↑, 1,   EZH2↓, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 1,   NSE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cachexia↓, 1,   chemoP↑, 1,  
Total Targets: 194

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5,   Catalase↑, 3,   GPx↑, 2,   GPx4∅, 1,   GSH↑, 3,   GSTs↑, 1,   HO-1↑, 6,   HO-1∅, 1,   lipid-P↓, 4,   MDA↓, 3,   NQO1↑, 2,   NRF2↑, 5,   NRF2∅, 1,   ROS↓, 7,   SOD↑, 5,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4∅, 1,   ALAT↓, 1,   AMPK↑, 1,   ATP↑, 1,   GSK‐3β↓, 1,   SIRT1↑, 1,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp1↓, 2,   proCasp1↓, 1,   Casp3↓, 3,   Casp9↓, 1,   Casp9↑, 1,   Ferroptosis↓, 1,   iNOS↓, 2,   Pyro↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

CREB↑, 1,   ERK↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ATF4↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   ER Stress↓, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

p‑γH2AX↓, 1,  

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

Diff↝, 1,  

Migration(tgid=13) ⓘ

TXNIP↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   IBI↑, 1,   ZO-1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IFN-γ↓, 1,   IL10↑, 1,   IL18↓, 1,   IL1β↓, 3,   IL2↓, 1,   IL33↓, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 4,   NF-kB↓, 1,   NLRP3↓, 2,   TLR4↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↓, 1,   BDNF↑, 1,   TPH1↓, 1,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,   BACE/β-secretase↓, 1,   tau↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARα↑, 1,   PPARγ↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BloodF↑, 1,   IL6↓, 3,  

Functional Outcomes(tgid=23) ⓘ

cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 1,   toxicity↓, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 2,  
Total Targets: 86

Scientific Paper Hit Count for: HO-1, HMOX1
16 Luteolin
2 Chemotherapy
1 Baicalein
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#:597  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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