Luteolin / ROS 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):

PI3K/AKT/mTOR survival signaling suppression, reducing proliferation and facilitating apoptosis, autophagy or other programmed cell-death responses.
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.
NF-κB and inflammatory survival signaling inhibition, with context-dependent suppression of TNF-α, IL-6, COX-2 and related inflammatory mediators.
Mitochondrial/intrinsic apoptosis activation through ↓ mitochondrial membrane potential, ↑ BAX:BCL-2 ratio, cytochrome-c release and caspase activation.
STAT3/JAK signaling suppression, reducing survival, stemness, inflammatory signaling and immune-evasion phenotypes in several tumor models.
EMT, migration and invasion suppression through modulation of E-cadherin, N-cadherin, vimentin, MMP2/MMP9, FAK, YAP/TAZ and related pathways.
Cell-cycle arrest through suppression of cyclins/CDKs and context-dependent induction of p21/p27 and p53 signaling.
Metabolic and hypoxic adaptation inhibition, including HIF-1α, PKM2, HK2 and glycolytic signaling in selected models.
Epigenetic modulation, including reported inhibition of DNMTs, HDAC-associated signaling and EZH2 in selected cancer models.
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↓">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.

ROS, Reactive Oxygen Species: Click to Expand ⟱

Source: HalifaxProj (inhibit)

Type:

Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination


Item  ROS↑  NRF2  Condition  Mechanism Class  Remarks  

ROS">Piperlongumine
+++  ↓  [D][T]  ROS-dominant
Selective <span class="wphighlight">ROS</span> stressor, Prevents compensatory upregulation of NRF2, ie GSH↓



ROS">Shikonin
+++ ↓/± [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + glycolysis + GPX4 inhibition



ROS">Vitamin K3 (menadione)
+++ ↓ [D] ROS-dominant
Quinone redox cycler; toxicity limits use



ROS">Copper (ionic / nano)
+++ ↓ [Fe][F] ROS-dominant
Fenton-type redox chemistry



ROS">Sodium Selenite
+++ ↓ [D] ROS-dominant
Pro-oxidant, depletes GSH



ROS">Juglone
+++ ↓ [D] ROS-dominant
Strong quinone <span class="wphighlight">ROS</span> chemistry



ROS">Auranofin
+++ ↓ [D] ROS-dominant
TrxR inhibition → redox collapse



ROS">Photodynamic Therapy (PDT)
+++ 0 [L][O₂] ROS-dominant
Singlet oxygen is core cytotoxic mechanism



ROS">Radiotherapy / Radiation
+++ 0 [O₂] ROS-dominant
DNA damage largely via <span class="wphighlight">ROS</span>



ROS">Doxorubicin
+++ ↓ [D] ROS-dominant
Chemo; redox cycling + mitochondrial <span class="wphighlight">ROS</span>



ROS">Cisplatin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> contributes to DNA/protein damage



ROS">Salinomycin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated CSC toxicity



ROS">Artemisinin / DHA
++ ↓ [Fe][T] ROS-dominant
Iron-activated radical generation



ROS">Sulfasalazine
++ ↓ [C][T] ROS-dominant
Ferroptosis; xCT inhibition → lipid <span class="wphighlight">ROS</span>



ROS">FMD / fasting
++ ↓ [M][C][O₂] ROS-dominant
Metabolic stress → mitochondrial <span class="wphighlight">ROS</span>



ROS">Vitamin C (pharmacologic)
++ ↓ [Fe][D] ROS-dominant
Extracellular H₂O₂ at high dose



ROS">Silver nanoparticles
++ ± [F][D] ROS-dominant
<span class="wphighlight">ROS</span> common; selectivity unreliable



ROS">Gambogic acid
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Parthenolide
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + NF-κB suppression



ROS">Plumbagin
++ ↓ [D] ROS-dominant
Quinone <span class="wphighlight">ROS</span> driver



ROS">Allicin
++ ↓ [D] ROS-dominant
Thiol-reactive oxidative stress



ROS">Ashwagandha (Withaferin A)
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Berberine
++ ↓ [D][M] ROS-dominant
Mitochondrial <span class="wphighlight">ROS</span> induction



ROS">PEITC
++ ↓ [D][C] ROS-dominant
GSH depletion + <span class="wphighlight">ROS</span>



ROS">Methionine restriction
+ ↓ [M][C][T] ROS-secondary
Redox vulnerability increased; <span class="wphighlight">ROS</span> indirect



ROS">DCA
+ ± [M][T] ROS-secondary
<span class="wphighlight">ROS</span> via forced OXPHOS



ROS">Capsaicin
+ ± [D][T] ROS-secondary
Ca²⁺ stress → <span class="wphighlight">ROS</span>



ROS">Galloflavin
+ 0 [D] ROS-secondary
<span class="wphighlight">ROS</span> not primary driver



ROS">Piperine
+ ± [D][F] ROS-secondary
Weak <span class="wphighlight">ROS</span> induction



ROS">Propyl gallate
+ ↓ [D] ROS-secondary
Pro-oxidant at high dose



ROS">Scoulerine
+ ? [D][T] ROS-secondary
Sparse <span class="wphighlight">ROS</span> data



ROS">Thymoquinone
± ± [D][T] Dual redox
Antioxidant ↔ pro-oxidant switch



ROS">Emodin
± ± [D][T] Dual redox
Not cancer-exclusive



ROS">Alpha-lipoic acid (ALA)
± ↑ [D][M] NRF2-dominant
Antioxidant at low dose



ROS">Curcumin
± ↑/↓ [D][F] NRF2-dominant
Hormetic redox behavior



ROS">EGCG
± ↑/↓ [D][O₂] NRF2-dominant
Auto-oxidation artifacts common



ROS">Quercetin
± ↑/↓ [D][Fe] NRF2-dominant
GSH-dependent cycling



ROS">Resveratrol
± ↑ [D][M] NRF2-dominant
<span class="wphighlight">ROS</span> only at high dose



ROS">Sulforaphane
± ↑↑ [D] NRF2-dominant
Strong NRF2 activator



ROS">Lycopene
0 ↑ — Antioxidant
Consistently antioxidant



ROS">Rosmarinic acid
0 ↑ — Antioxidant
Primarily antioxidant



ROS">Citrate
0 0 — Neutral
Metabolic; not a <span class="wphighlight">ROS</span> agent

Scientific Papers found: Click to Expand⟱

2625-

Ba,

LT,

Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte

in-vivo,

Stroke,

rat

*lipid-P↓, *ACSL4∅, *NRF2∅, *GPx4∅, *Ferroptosis↓, *ROS↓, *MDA↓, *eff↑, *HO-1∅,

8370-

LT,

Luteolin Induces GPX4-dependent Ferroptosis and Enhances Immune Activation in Colon Cancer

vitro+vivo,

Colon,

TumCP↓, ROS↑, Iron↑, lipid-P↑, MDA↑, GSH↓, GPx4↓, Ferroptosis↑, pol-M1↑, CD8+↑, Imm↑,

8368-

LT,

A critical role of luteolin-induced reactive oxygen species in blockage of tumor necrosis factor-activated nuclear factor-kappaB pathway and sensitization of apoptosis in lung cancer cells

in-vitro,

Lung,

NF-kB↓, ROS↑, JNK↑, Apoptosis↑, SOD↓, eff↓,

8377-

LT,

Luteolin: exploring its therapeutic potential and molecular mechanisms in pulmonary diseases

Review,

Asthma,

*PI3K↑, *Akt↑, *Inflam↓, *ROS↓, *BioAv↓, *RenoP↑, *cardioP↑, *neuroP↑, *antiAll↑, *AntiDiabetic↑, *hepatoP↑, *AntiThr↑, *toxicity↓, *IL10↓, *Sepsis↓, *TNF-α↓, *ROS↓, *GSH↑, *Catalase↑, *SOD↑, *MDA↓, *lipid-P↓, *IL4↓, *IL5↓, *PGE2↓, *PI3K↑, *Akt↑, *mTOR↑, *Beclin-1/ATG6↓, *Mucositis↓, *PLA2↓, STAT3↓, PD-L1↓, miR-34a↓, Casp3↑, Casp9↑, Bcl-2↓, BAX↑, Bax:Bcl2↑, Apoptosis↑, ROS↑, EMT↓, E-cadherin↓, DR5↑, LIMK1↓, Pain↓,

8378-

LT,

Luteolin and its derivatives: modulation of epithelial-mesenchymal transition in fibrosis and cancer

Review,

Var,

EMT↓, TGF-β1↓, Smad1↓, PI3K↓, Akt↓, Hippo↝, YAP/TEAD↓, *NRF2↑, *HO-1↑, *ROS↓, E-cadherin↑, ZO-1↑, Vim↓, CLDN1↓, β-catenin/ZEB1↓, Snail↓, TCF↓, Zeb1↓, angioG↓, eff↑, ROS↑, mtDam↑, MMP↓, ETC↓,

8379-

LT,

Luteolin and neuroinflammation: a multi-target therapeutic strategy for central nervous system disorders

Review,

Var,

Review,

AD,

Review,

Stroke,

*neuroP↑, *Inflam↓, *ROS↓, *Apoptosis↓, *BioAv↓, *BBB∅, Ferroptosis↑, ROS↑, Iron↑, lipid-P↑, MDA↑, GSH↓, GPx4↓, *Aβ↓, *memory↑, *neuroG↑, *NRF2↑, *NLRP3↓, *ROS↓, JAK2↓, STAT3↓, PD-L1↓, Perforin↝, GranB/GZMB↝, hepatoP↑, *Learn↑, *TNF-α↓, *IL1β↓, *IL6↓, *NO↓, *COX2/PTGS2↓, *iNOS↓, *ER Stress↓, *GRP78/BiP↓, *IRE1↓, *cognitive↑, *BAX↓, *Bcl-2↓, *Casp3↓, *PSD95↑, *SNAP25↑, *JNK↓, *eff↑, *mtDam↓, *MMP↑, *Stroke↓, *TJ↑, *MMP9↓, *BBB∅, *NeuroI↓,

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↓, TumCP↓, ROS↑, BAX↑, cl‑Casp9↑, Beclin-1/ATG6↑, LC3B-II↑, Bcl-2↓, p62↓, TumAuto↑, p‑Akt↓, p‑mTOR↓, HO-1↓,

8382-

LT,

Luteolin as a dietary flavonoid for brain health: modulating neuroinflammation and cognitive decline in neurodegenerative disorders

Review,

AD,

Review,

Park,

*neuroP↑, *Inflam↓, *antiOx↑, *NF-kB↓, *NRF2↑, *BDNF↑, *cognitive↑, *motorD↑, *BBB↑, *BioAv↓, *NO↓, *ROS↓, *NRF2↑, *ARE↑, *MMP↑, *BDNF↑, *Learn↑, *memory↑, *cognitive↑, *p‑JNK↓, *GFAP↓, *AIF1/Iba-1↓, *TNF-α↓, *IL1β↓, *BAX↓, *COX2/PTGS2↓, *BACE/β-secretase↓, *Aβ42↓, *PSD95↑, *SNAP25↑, *lipid-P↓, *GSTs↓, *GSH↑, *SOD↓, *Catalase↓, *AChE↓, *Casp3↓, *Casp9↓,

8367-

LT,

Role of Luteolin in Prevention of Oral, Esophageal, Gastric, Pancreatic, and Colon Cancers: Recent Trends and Future Perspectives

Review,

Var,

*antiOx↑, ROS↓, Inflam↓, Apoptosis↑,

7825-

LT,

MBS,

Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review

Review,

AD,

*neuroP↑, *OS↑, *antiOx↑, *Aβ42↓, *AChE↓, *Aβ↓, *IRes↓, *p‑tau↓, *ROS↓, *Apoptosis↓, *Inflam↓, *Iron↝,

4339-

LT,

Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis

in-vivo,

Nor,

C57BL/6 male mice

*AntiAg↑, *ROS↓,

4338-

LT,

Luteolin: a natural product with multiple mechanisms for atherosclerosis

Review,

Var,

*Inflam↓, *ROS↓, *PDGF↓, *lipid-P↓, *AMPK↑, *SIRT1↑, *AntiAg↑,

8393-

LT,

Progress, pharmacokinetics and future perspectives of luteolin modulating signaling pathways to exert anticancer effects: A review

Review,

Var,

TumCP↓, TumMeta↓, angioG↓, EMT↓, Imm↝, ChemoSen↑, *Inflam↓, *COX2/PTGS2↓, *NF-kB↓, MMP2↓, MMP9↓, p‑Akt↓, p‑PI3K↓, IGF-2↓, IGF-1R↓, CXCL16↓, NOTCH1↓, HES1↓, VEGF↓, ROS↑,

8405-

LT,

Rad,

Luteolin's role as a radiosensitizer by promoting cell death and ROS modulation

Review,

NSCLC,

RadioS↑, ROS↑,

8403-

LT,

Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells

in-vitro,

CRC,

HT-29

tumCV↓, selectivity↑, Apoptosis↑, Casp↑, MMP↓, Ca+2↑, BAX↑, Bcl-2↓, Cyt‑c↑, Casp9↑, Casp3↑, ROS↓, SOD↑, Catalase↑, GSH↑, antiOx↑, MAPK↑,

8402-

LT,

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

vitro+vivo,

CRC,

T24/HTB-9

nude mice

tumCV↓, TumCCA↑, p‑S6↓, P21↑, Trx1↑, ROS↓, Ki-67↓, mTOR↓, TumCP↓,

8401-

LT,

Multi-Faceted Role of Luteolin in Cancer Metastasis: EMT, Angiogenesis, ECM Degradation and Apoptosis

Review,

Var,

EMT↓, N-cadherin↓, Vim↓, VEGF↓, VEGFR1↓, MMPs↓, Telomerase↓, NF-kB↓, cMyc↓, Bax:Bcl2↑, Casp3↑, PI3K↓, Akt↓, FOXO3↑, P21↑, p27/CDKN1B↑, cl‑PARP↑, Cyt‑c↑, NOTCH↓, HES1↓, ROS↑, SOD↓, miR-34b-5p↑, Hif1a↓, P21↓, survivin↓, Mcl-1?, Bcl-xL↓, MDM2↓, MMP2↓, MMP9↓, MMP3↓, MMP16↓, miR-384↑, NRF2↓, HO-1↓, angioG↓,

8399-

LT,

Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer's disease

in-vivo,

AD,

 AD (3 × Tg-AD) mice

*memory↑, *cognitive↑, *neuroP↑, *Aβ↓, *mtDam↓, *Apoptosis↓, *PPARγ↑, *ROS↓, *SOD↑, *GSH↑, *NRF2↑, *MFN2↑, *DRP1/DNM1L↓, *FIS1↓, *Bcl-2↑, *BAX↓, *Cyt‑c↓, *cl‑Casp9↓, *cl‑Casp3↓, *IDE↑, *BACE/β-secretase↓, *Aβ42↓,

8398-

LT,

Luteolin: Nature's promising warrior against Alzheimer's and Parkinson's disease

Review,

AD,

Review,

Park,

*antiOx↑, *Inflam↓, *AntiBio↑, *AntiCan↑, *hepatoP↑, *neuroP↑, *cardioP↑, *neuroG↑, *BBB↑, *ROS↓, *AChE↓, *p‑T-cadherin↓, *Aβ↓, *memory↑, *TNF-α↓, *IL1β↓, *MCP1/CCL2↓, *RANTES↓, *BioAv↑, *Half-Life↝, *toxicity↓, *BACE/β-secretase↓, *Aβ42↓, *COX2/PTGS2↓, *Bcl-2↓, *Casp3↓, *BAX↓, *GSTs↓, *lipid-P↓, *Casp3↓, *Casp9↓, *memory↑, *GSK‐3β↓, *ChAT↑, *SOD↑, *GPx↑, *MDA↓, *ER Stress↓, *GRP78/BiP↓, *NRF2↑, *motorD↑, *antiAll↑,

8396-

LT,

Myr,

KAE,

QC,

Api

Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases

in-vivo,

Nor,

*other↝, *AntiAg↑, *ROS↓,

8394-

LT,

Luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation

in-vitro,

Nor,

*Pyro↓, *NLRP3↓, *proCasp1↓, *Casp1↓, *NRF2↑, *HO-1↑, *ROS↓,

8390-

LT,

Luteolin in Inflammatory Bowel Disease and Colorectal Cancer: A Disease Continuum Perspective

Review,

IBD,

Review,

CRC,

*Diff↝, *Inflam↓, *ROS↓, *GutMicro↑, *IBI↑, TumCP↓, Apoptosis↑, TumCMig↓, TumCI↓, *BioAv↑, *iNOS↓, *TNF-α↓, *IL6↓, *MDA↓, *lipid-P↓, *antiOx↑, *NRF2↑, *HO-1↑, *NQO1↑, *SOD↑, *Catalase↑, *5HT↓, *TPH1↓, *MAPK↓, *ERK↓, *Inflam↓, cycD1/CCND1↓, CDK4↓, TumCCA↑, Casp3↑, Casp9↑, PI3K↓, Akt↓, p‑Akt↓, p‑mTOR↓, E-cadherin↑, N-cadherin↓, Vim↓,

8389-

LT,

Luteolin-Manganese Nanozyme Induces Apoptosis and Ferroptosis for Enhanced Cancer Therapy

in-vitro,

Var,

ROS↑, Apoptosis↑, cl‑Casp3↑, cl‑Casp9↑, Ferroptosis↑, NRF2↓, GPx4↓, IronCh↑,

8386-

LT,

Luteolin induces apoptosis in Philadelphia chromosome-positive acute lymphoblastic leukemia cell by regulating the PI3K/AKT signaling pathway

in-vitro,

ALL,

SUP-B15

tumCV↓, ROS↑, MMP↓, ATP↓, p‑PI3K↓, p‑Akt↓, p‑STAT3↓, Bcl-2↓, BAX↑, cl‑Casp3↑, cl‑Casp9↑, TumCP↓, eff↓, ChemoSen↑, FAK↓, Synergy↑, BioAv↓, BioAv↑,

8384-

LT,

Current situation and research progress of luteolin in the treatment of gastrointestinal malignant tumors

Review,

GC,

Apoptosis↑, TumAuto↑, TumCCA↑, EMT↓, *ROS↓, *antiOx↑, ROS↑, P53↑, LC3II↑, Beclin-1/ATG6↑, p‑MAP2K1/MEK1↓, p‑ERK↓, BAX↑, cl‑Casp3↑, Bcl-2↓, p‑MAPK↓, DNArepair↓, HMGB1↓, XRCC1↓, ERCC3↑, CycB/CCNB1↓, CDC2↓, p‑CHK1↑, TumCCA↑, TumCP?, Wnt↓, β-catenin/ZEB1↓, miR-384↑, PTN↓, MMP2↓, MMP3↓, MMP9↓, MMP16↓, Ferroptosis↑, GPx4↓, Synergy↑, Ki-67↓, GSH↓, ChemoSen↑, TumCP↓, TumCMig↓, TumCI↓, PI3K↓, Akt↓, mTOR↓, NF-kB↓, NOTCH↓, miR-139-5p↑, miR-34a↑, miR-422a↑, miR-107↑, miR-21↓, miR-155↓, miR-224↓, miR-340↓, E-cadherin↑, N-cadherin↓, Vim↓, HK1↓, FOXO1↓, compI↓, compIII↓, compV↓, ETC↓, BioAv↝,

4292-

LT,

Luteolin for neurodegenerative diseases: a review

Review,

AD,

Review,

Park,

Review,

MS,

Review,

Stroke,

*Inflam↓, *antiOx↑, *neuroP↑, *BioAv↝, *BBB↑, *TNF-α↓, *IL1β↓, *IL6↓, *IL8↓, *IL33↓, *NF-kB↓, *BACE/β-secretase↓, *ROS↓, *SOD↑, *HO-1↑, *NRF2↑, *Casp3↓, *Casp9↑, *Bax:Bcl2↓, *UPR↑, *GRP78/BiP↑, *Aβ↓, *GSK‐3β↓, *tau↓, *CREB↑, *ATP↑, *cognitive↑, *BloodF↑, *BDNF↑, *TrkB↑, *memory↑, *PPARγ↑, *Synergy↑,

2907-

LT,

Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems

in-vitro,

Nor,

Chinese hamster lung fibroblasts (V79-4)

*ROS↓, *Casp9↓, *Casp3↓, *Bcl-2↑, *BAX↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *HO-1↑, *antiOx↑, *lipid-P↓, *p‑γH2AX↓, eff↑,

2906-

LT,

Luteolin, a flavonoid with potentials for cancer prevention and therapy

Review,

Var,

*Inflam↓, AntiCan↑, antiOx⇅, Apoptosis↑, TumCP↓, TumMeta↓, angioG↓, PI3K↓, Akt↓, NF-kB↓, XIAP↓, P53↑, *ROS↓, *GSTA1↑, *GSR↑, *SOD↑, *Catalase↑, *other↓, ROS↑, Dose↝, chemoP↑, NF-kB↓, JNK↑, p27/CDKN1B↑, P21↑, DR5↑, Casp↑, Fas↑, BAX↑, MAPK↓, CDK2↓, IGF-1↓, PDGF↓, EGFR↓, PKCδ↓, TOP1↓, TOP2↓, Bcl-xL↓, FASN↓, VEGF↓, VEGFR2/KDR/Flk1↓, MMP9↓, Hif1a↓, FAK↓, MMP1↓, Twist↓, ERK↓, P450↓, CYP1A1↓, CYP1A2↓, TumCCA↑,

2905-

LT,

Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions

in-vivo,

Nor,

HMrSV5

C57/BL6 mice were used in vivo experiments

*ROS↓, *p‑Akt↓, *Vim↓, *E-cadherin↑, *PI3K↓,

2904-

LT,

Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons

in-vitro,

Park,

SK-N-SH

in-vitro,

AD,

*ROS↓, *neuroP↑, *MMP↑, *Catalase↑, *GSH↑, selectivity↑, *eff↑, *Cyt‑c↓,

2903-

LT,

Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma

in-vitro,

GBM,

U251

in-vitro,

GBM,

U87MG

in-vivo,

NA,

mouse

ER Stress↑, ROS↑, PERK↑, eIF2α↑, ATF4↑, CHOP/DDIT3↑, Casp12↑, eff↓, UPR↑, MMP↓, Cyt‑c↑, Bcl-2↓, BAX↑, TumCG↓, Weight∅, ALAT∅, AST∅,

2908-

LT,

Luteolin attenuates neutrophilic oxidative stress and inflammatory arthritis by inhibiting Raf1 activity

in-vitro,

Arthritis,

*ROS↓, *p‑ERK↓, *p‑MEK↓, *Raf↓,

1100-

LT,

Luteolin, a flavonoid, as an anticancer agent: A review

Review,

Var,

TumCP↓, TumCCA↑, Apoptosis↑, EMT↓, E-cadherin↑, N-cadherin↓, Snail↓, Vim↓, ROS↑, ER Stress↑, mtDam↑, p‑eIF2α↝, p‑PERK↝, p‑CHOP/DDIT3↝, p‑ATF4↝, cl‑Casp12↝,

1084-

LT,

CHr,

Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells

in-vitro,

Nor,

RAW264.7

*COX2/PTGS2↓, *COX2/PTGS2∅, *PGE2↓, *ROS↓,

2921-

LT,

Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies

Review,

Nor,

*hepatoP↑, *AMPK↑, *SIRT1↑, *ROS↓, STAT3↓, TNF-α↓, NF-kB↓, *IL2↓, *IFN-γ↓, *GSH↑, *SREBP1/SREBF1↓, *ZO-1↑, *TLR4↓, BAX↑, Bcl-2↓, XIAP↓, Fas↑, Casp8↑, Beclin-1/ATG6↑, *TXNIP↓, *Casp1↓, *IL1β↓, *IL18↓, *NLRP3↓, *MDA↓, *SOD↑, *NRF2↑, *ER Stress↓, *ALAT↓, *AST↓, *iNOS↓, *IL6↓, *HO-1↑, *NQO1↑, *PPARα↑, *ATF4↓, *CHOP/DDIT3↓, *Inflam↓, *antiOx↑, *GutMicro↑,

2930-

LT,

Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320

in-vitro,

Nor,

rats

*RenoP↑, *ROS↓, *antiOx↑, *NRF2↓,

2922-

LT,

Combination of transcriptomic and proteomic approaches helps unravel the mechanisms of luteolin in inducing liver cancer cell death via targeting AKT1 and SRC

in-vitro,

Liver,

HUH7

 12.68 µM

Half-Life↝, TumCCA↑, AKT1↓, ATF2↓, NF-kB↓, GSK‐3β↓, cMyc↓, GSTs↓, TrxR1↓, ROS↑,

2919-

LT,

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence

Review,

Var,

RadioS↑, ChemoSen↑, chemoP↑, *lipid-P↓, *Catalase↑, *SOD↑, *GPx↑, *GSTs↑, *GSH↑, *TNF-α↓, *IL1β↓, *Casp3↓, *IL10↑, NRF2↓, HO-1↓, NQO1↓, GSH↓, MET↓, p‑MET↓, p‑Akt↓, HGF/c-Met↓, NF-kB↓, Bcl-2↓, SOD2↓, Casp8↑, Casp3↑, PARP↑, MAPK↓, NLRP3↓, ASC↓, Casp1↓, IL6↓, IKKα↓, p‑p65↓, p‑p38↑, MMP2↓, ICAM-1↓, EGFR↑, p‑PI3K↓, E-cadherin↓, ZO-1↑, N-cadherin↓, CLDN1↓, β-catenin/ZEB1↓, Snail↓, Vim↑, ITGB1↓, FAK↓, p‑Src↓, Rac1↓, Cdc42↓, Rho↓, PCNA↓, Tyro3↓, AXL↓, CEA↓, NSE↓, SOD↓, Catalase↓, GPx↓, GSR↓, GSTs↓, GSH↓, VitE↓, VitC↓, CYP1A1↓, cFos↑, AR↓, AIF↑, p‑STAT6↓, p‑MDM2↓, NOTCH1↓, VEGF↓, H3↓, H4↓, HDAC↓, SIRT1↓, ROS↑, DR5↑, Cyt‑c↑, p‑JNK↑, PTEN↓, mTOR↓, CD34↓, FasL↑, Fas↑, XIAP↓, p‑eIF2α↑, CHOP/DDIT3↑, LC3II↑, PD-1↓, STAT3↓, IL2↑, EMT↓, cachexia↓, BioAv↑, *Half-Life↝, *eff↑,

2918-

LT,

Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS

in-vitro,

Melanoma,

A375

in-vivo,

Melanoma,

in-vitro,

Melanoma,

SK-MEL-28

TumCG↓, ROS↑, ECM/TCF↓,

2917-

LT,

Rad,

Luteolin acts as a radiosensitizer in non‑small cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade

in-vitro,

Lung,

Bcl-2↓, Casp3↑, Casp8↑, Casp9↑, p‑p38↑, ROS↑, RadioS↑,

2916-

LT,

Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies

Review,

Var,

Review,

AD,

Review,

Park,

proCasp9↓, CDC2↓, CycB/CCNB1↓, Casp9↑, Casp3↑, Cyt‑c↑, cycA1/CCNA1↑, CDK2↓, APAF1↑, TumCCA↑, P53↑, BAX↑, VEGF↓, Bcl-2↓, Apoptosis↑, p‑Akt↓, p‑EGFR↓, p‑ERK↓, p‑STAT3↓, cardioP↑, Catalase↓, SOD↓, *BioAv↓, *antiOx↑, *ROS↓, *NO↓, *GSTs↑, *GSR↑, *SOD↑, *Catalase↑, *lipid-P↓, PI3K↓, Akt↓, CDK2↓, BNIP3↑, hTERT/TERT↓, DR5↑, Beclin-1/ATG6↑, TNF-α↓, NF-kB↓, IL1↓, IL6↓, EMT↓, FAK↓, E-cadherin↑, MDM2↓, NOTCH↓, MAPK↑, Vim↓, N-cadherin↓, Snail↓, MMP2↓, Twist↓, MMP9↓, ROS↑, MMP↓, *AChE↓, *MMP↑, *Aβ↓, *neuroP↑, Trx1↑, ROS↓, *NRF2↑, NRF2↓, *BBB↑, ChemoSen↑, GutMicro↑, *antiAll↑, *Mucositis↓, *TregCell↑, *Beclin-1/ATG6↓, *PI3K↑, *Akt↑, *mTOR↑,

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

30 μM

in-vitro,

CRC,

SNU-407

30 μM

in-vitro,

Nor,

FHC

65 μM

DNMTs↓, TET1↑, NRF2↑, HDAC↓, tumCV↓, BAX↑, Casp9↑, Casp3↑, Bcl-2↓, ROS↓, GSS↑, Catalase↑, HO-1↑, DNMT1↓, DNMT3A↓, TET1↑, TET3↑, TET2↓, P53↑, P21↑,

2914-

LT,

Therapeutic Potential of Luteolin on Cancer

Review,

Var,

3–50 µM in vitro

*antiOx↑, *IronCh↑, *toxicity↓, *BioAv↓, *BioAv↑, DNAdam↑, TumCP↓, DR5↑, P53↑, JNK↑, BAX↑, cl‑Casp3↑, cl‑Casp8↑, cl‑Casp9↑, cl‑PARP↑, survivin↓, cycD1/CCND1↓, CycB/CCNB1↓, CDC2↓, P21↑, angioG↓, MMP2↓, AEG1↓, VEGF↓, VEGFR2/KDR/Flk1↓, MMP9↓, CXCR4↓, PI3K↓, Akt↓, ERK↓, TumAuto↑, LC3B-II↑, EMT↓, E-cadherin↑, N-cadherin↓, Wnt↓, ROS↑, NICD↓, p‑GSK‐3β↓, iNOS↓, COX2/PTGS2↓, NRF2↑, Ca+2↑, ChemoSen↑, ChemoSen↓, IFN-γ↓, RadioS↑, MDM2↓, NOTCH1↓, AR↓, TIMP1↑, TIMP2↑, ER Stress↑, CDK2↓, Telomerase↓, p‑NF-kB↑, p‑cMyc↑, hTERT/TERT↓, RAS↓, YAP/TEAD↓, TAZ↓, NF-kB↓, NRF2↓, HO-1↓, MDR1↓,

2913-

LT,

Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells

in-vitro,

GC,

HGC27

0, 10, 20, 30, 40, 50, 60, 70, and 80 µM) for 24 h or 48 h

in-vitro,

BC,

MCF7

in-vitro,

GC,

MKN45

TumCP↓, MMP↓, Apoptosis↑, ROS↑, SOD↓, ATP↓, Bax:Bcl2↑, TumCCA↑,

2912-

LT,

Luteolin: a flavonoid with a multifaceted anticancer potential

Review,

Var,

ROS↑, TumCCA↑, TumCP↓, angioG↓, ER Stress↑, mtDam↑, PERK↑, ATF4↑, eIF2α↑, cl‑Casp12↑, EMT↓, E-cadherin↑, N-cadherin↓, Vim↓, *neuroP↑, NF-kB↓, PI3K↓, Akt↑, XIAP↓, MMP↓, Ca+2↑, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, Cyt‑c↑, IronCh↑, SOD↓, *ROS↓, *LDHA↑, *SOD↑, *GSH↑, *BioAv↓, Telomerase↓, cMyc↓, hTERT/TERT↓, DR5↑, Fas↑, FADD↑, BAD↑, BOK↑, BID↑, NAIP↓, Mcl-1↓, CDK2↓, CDK4↓, MAPK↓, AKT1↓, Akt2↓, *Beclin-1/ATG6↓, Hif1a↓, LC3II↑, Beclin-1/ATG6↑,

2911-

LT,

Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes

in-vitro,

Nor,

HaCaT

*MMP1↓, *COX2/PTGS2↓, *IL6↓, *AP-1↓, *NF-kB↓, *ROS↓, *p‑MKK4↑, *p‑JNK↓, *p‑p38↓,

Showing Research Papers: 1 to 46 of 46

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 46

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,
Total Targets: 300

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 12, ARE↑, 1, Catalase↓, 1, Catalase↑, 7, GPx↑, 3, GPx4∅, 1, GSH↑, 8, GSR↑, 2, GSTs↓, 2, GSTs↑, 2, HO-1↑, 6, HO-1∅, 1, Iron↝, 1, lipid-P↓, 9, MDA↓, 5, NQO1↑, 2, NRF2↓, 1, NRF2↑, 11, NRF2∅, 1, ROS↓, 28, SOD↓, 1, SOD↑, 11,

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

DRP1/DNM1L↓, 1, FIS1↓, 1, MFN2↑, 1, mtDam↓, 2,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4∅, 1, ALAT↓, 1, AMPK↑, 2, ATP↑, 1, GSK‐3β↓, 2, LDHA↑, 1, PLA2↓, 1, SIRT1↑, 2, SREBP1/SREBF1↓, 1,

Cell Death(tgid=5) ⓘ

Apoptosis↓, 3, BAX↓, 5, Bax:Bcl2↓, 1, Bcl-2↓, 2, Bcl-2↑, 2, Casp1↓, 2, proCasp1↓, 1, Casp3↓, 7, cl‑Casp3↓, 1, Casp9↓, 3, Casp9↑, 1, cl‑Casp9↓, 1, Cyt‑c↓, 2, Ferroptosis↓, 1, iNOS↓, 3, p‑p38↓, 1, Pyro↓, 1,

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↑, 3, p‑Akt↓, 1, CREB↑, 1, ERK↓, 1, p‑ERK↓, 1, JNK↓, 1, p‑JNK↓, 2, MAPK↓, 1, p‑MEK↓, 1, p‑MKK4↑, 1, mTOR↑, 2, PI3K↓, 1, PI3K↑, 3, Raf↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1, ATF4↓, 1, other↓, 1, other↝, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1, ER Stress↓, 3, GRP78/BiP↓, 2, GRP78/BiP↑, 1, IRE1↓, 1, UPR↑, 1,

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↓, 3,

DNA Damage & Repair(tgid=10) ⓘ

p‑γH2AX↓, 1,

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

Diff↝, 1, neuroG↑, 2,

Migration(tgid=13) ⓘ

AntiAg↑, 3, AP-1↓, 1, E-cadherin↑, 1, MMP1↓, 1, MMP9↓, 1, PDGF↓, 1, p‑T-cadherin↓, 1, TregCell↑, 1, TXNIP↓, 1, Vim↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 3,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 4, BBB∅, 2, IBI↑, 1, MMP↑, 4, TJ↑, 1, ZO-1↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

AIF1/Iba-1↓, 1, COX2/PTGS2↓, 6, COX2/PTGS2∅, 1, IFN-γ↓, 1, IL10↓, 1, IL10↑, 1, IL18↓, 1, IL1β↓, 6, IL2↓, 1, IL33↓, 1, IL4↓, 1, IL5↓, 1, IL6↓, 5, IL8↓, 1, Inflam↓, 12, MCP1/CCL2↓, 1, NeuroI↓, 1, NF-kB↓, 4, NLRP3↓, 3, PGE2↓, 2, RANTES↓, 1, TLR4↓, 1, TNF-α↓, 7,

Cellular Microenvironment(tgid=17) ⓘ

GFAP↓, 1,

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↓, 1, AChE↓, 4, BDNF↑, 3, ChAT↑, 1, PSD95↑, 2, SNAP25↑, 2, TPH1↓, 1, TrkB↑, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 6, Aβ42↓, 4, BACE/β-secretase↓, 4, IDE↑, 1, tau↓, 1, p‑tau↓, 1,

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARα↑, 1, PPARγ↑, 2,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 6, BioAv↑, 3, BioAv↝, 1, eff↑, 4, GSTA1↑, 1, Half-Life↝, 2, Synergy↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1, BloodF↑, 1, IL6↓, 5, IRes↓, 1,

Functional Outcomes(tgid=23) ⓘ

antiAll↑, 3, AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 2, cognitive↑, 5, hepatoP↑, 3, Learn↑, 2, memory↑, 6, motorD↑, 2, Mucositis↓, 2, neuroP↑, 10, OS↑, 1, RenoP↑, 2, Stroke↓, 1, toxicity↓, 3,

Infection & Microbiome(tgid=24) ⓘ

AntiBio↑, 1, GutMicro↑, 2, Sepsis↓, 1,
Total Targets: 168

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species

46 Luteolin
2 Radiotherapy/Radiation
1 Baicalein
1 Mung Bean Sprouts
1 Myricetin
1 Kaempferol
1 Quercetin
1 Apigenin (mainly Parsley)
1 Chrysin

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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Luteolin / ROS Cancer Research Results

Common Dietary and Plant Sources of Luteolin

Luteolin — Cancer Mechanisms

Luteolin — Alzheimer’s Disease Mechanisms

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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