Luteolin / Casp3 Cancer Research Results

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

-Note half-life 2–3 hours
BioAv low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
Pathways:
- induce ROS production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

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


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
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↑, LC3II↑, PD-1↓, STAT3↓, IL2↑, EMT↓, cachexia↓, BioAv↑, *Half-Life↝, *eff↑,
2923- LT,    Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells
- in-vitro, NA, NA
Apoptosis↑, TumCD↑, Casp12↑, Casp9↑, Casp3↑, ER Stress↑, CHOP↑, GRP78/BiP↑, GRP94↑, cl‑ATF6↑, p‑eIF2α↑, MMP↓, JNK↓, p38↑, ERK↑, Cyt‑c↑,
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, NA
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, NA - Review, AD, NA - Review, Park, NA
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↑, 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↑,
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↓, 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, NA
*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↓, MMP9↓, CXCR4↓, PI3K↓, Akt↓, ERK↓, TumAuto↑, LC3B-II↑, EMT↓, E-cadherin↑, N-cadherin↓, Wnt↓, ROS↑, NICD↓, p‑GSK‐3β↓, iNOS↓, COX2↓, 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↓,
2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
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↓, Hif1a↓, LC3II↑, Beclin-1↑,
4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, *antiOx↑, *neuroP↑, *BioAv↝, *BBB↑, *TNF-α↓, *IL1β↓, *IL6↓, *IL8↓, *IL33↓, *NF-kB↓, *BACE↓, *ROS↓, *SOD↑, *HO-1↑, *NRF2↑, *Casp3↓, *Casp9↑, *Bax:Bcl2↓, *UPR↑, *GRP78/BiP↑, *Aβ↓, *GSK‐3β↓, *tau↓, *CREB↑, *ATP↑, *cognitive↑, *BloodF↑, *BDNF↑, *TrkB↑, *memory↑, *PPARγ↑, *eff↑,
1064- LT,  Cisplatin,    Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells
- vitro+vivo, Lung, LNM35 - in-vitro, CRC, HT-29 - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Casp3↑, Casp7↑, HDAC↓,
2907- LT,    Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems
- in-vitro, Nor, NA
*ROS↓, *Casp9↓, *Casp3↓, *Bcl-2↑, *BAX↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *HO-1↑, *antiOx↑, *lipid-P↓, *p‑γH2AX↓, eff↑,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 2,   Catalase↑, 1,   CYP1A1↓, 1,   GPx↓, 1,   GSH↓, 2,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 1,   HO-1↓, 2,   HO-1↑, 1,   NQO1↓, 1,   NRF2↓, 3,   NRF2↑, 2,   ROS↓, 2,   ROS↑, 5,   SOD↓, 3,   SOD2↓, 1,   Trx1↑, 1,   VitC↓, 1,   VitE↓, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   BOK↑, 1,   CDC2↓, 2,   MMP↓, 3,   mtDam↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   cMyc↓, 1,   p‑cMyc↑, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   p‑Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 2,   BAD↑, 1,   BAX↑, 4,   Bcl-2↓, 5,   BID↑, 1,   Casp1↓, 1,   Casp12↑, 1,   cl‑Casp12↑, 1,   Casp3↑, 7,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 5,   cl‑Casp9↑, 1,   proCasp9↓, 1,   Cyt‑c↑, 4,   DR5↑, 4,   FADD↑, 1,   Fas↑, 2,   FasL↑, 1,   HGF/c-Met↓, 1,   hTERT/TERT↓, 3,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 1,   p‑JNK↑, 1,   MAPK↓, 2,   MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 2,   p‑MDM2↓, 1,   NAIP↓, 1,   NICD↓, 1,   p38↑, 1,   p‑p38↑, 2,   survivin↓, 1,   Telomerase↓, 2,   TumCD↑, 1,   YAP/TEAD↓, 1,  

Transcription & Epigenetics ⓘ

H3↓, 1,   H4↓, 1,   TET3↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

cl‑ATF6↑, 1,   CHOP↑, 2,   eIF2α↑, 1,   p‑eIF2α↑, 2,   ER Stress↑, 3,   GRP78/BiP↑, 1,   GRP94↑, 1,   PERK↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   BNIP3↑, 1,   LC3B-II↑, 1,   LC3II↑, 2,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 1,   P53↑, 3,   PARP↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 4,   CDK4↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   cFos↑, 1,   EMT↓, 4,   ERK↓, 1,   ERK↑, 1,   p‑ERK↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 3,   mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 2,   PI3K↓, 3,   p‑PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   p‑STAT6↓, 1,   TAZ↓, 1,   Wnt↓, 1,  

Migration ⓘ

AEG1↓, 1,   Akt2↓, 1,   AXL↓, 1,   Ca+2↑, 2,   Cdc42↓, 1,   CEA↓, 1,   CLDN1↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 3,   FAK↓, 2,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP2↓, 3,   MMP9↓, 2,   N-cadherin↓, 4,   Rac1↓, 1,   Rho↓, 1,   Snail↓, 2,   TET1↑, 2,   TIMP1↑, 1,   TIMP2↑, 1,   TumCP↓, 2,   Twist↓, 1,   Tyro3↓, 1,   Vim↓, 2,   Vim↑, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↑, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 3,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   COX2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL2↑, 1,   IL6↓, 2,   NF-kB↓, 4,   p‑NF-kB↑, 1,   p‑p65↓, 1,   PD-1↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 3,   eff↑, 1,   MDR1↓, 1,   RadioS↑, 3,   TET2↓, 1,  

Clinical Biomarkers ⓘ

AR↓, 2,   CEA↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   GutMicro↑, 1,   hTERT/TERT↓, 3,   IL6↓, 2,   NSE↓, 1,  

Functional Outcomes ⓘ

cachexia↓, 1,   cardioP↑, 1,   chemoP↑, 1,  
Total Targets: 198

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 3,   GPx↑, 2,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 2,   HO-1↑, 2,   lipid-P↓, 3,   NRF2↑, 2,   ROS↓, 4,   SOD↑, 5,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,   LDHA↑, 1,   PPARγ↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp3↓, 3,   Casp9↓, 1,   Casp9↑, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,  

DNA Damage & Repair ⓘ

p‑γH2AX↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

IL10↑, 1,   IL1β↓, 2,   IL33↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,   tau↓, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 2,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

BloodF↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   neuroP↑, 3,   toxicity↓, 1,  
Total Targets: 55

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
10 Luteolin
1 Radiotherapy/Radiation
1 Cisplatin
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#:42  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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