condition found tbRes List
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.

*** ACTIVE WORK IN PROGRESS**

-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


FAK, FAK signaling: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
FAK (Focal Adhesion Kinase) is a non-receptor tyrosine kinase that plays a crucial role in cellular processes such as adhesion, migration, proliferation, and survival. It is primarily localized at focal adhesions, where it interacts with integrins and other signaling molecules. FAK promotes cell proliferation by activating signaling pathways such as the PI3K/Akt and MAPK/ERK pathways. These pathways are often upregulated in cancer cells, leading to uncontrolled growth.
Scientific Papers found: Click to Expand⟱
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↓, , by inactivating proteins; such as procaspase‐9, CDC2 and cyclin B or upregulation of caspase‐9 and caspase‐3, cytochrome C, cyclin A, CDK2, and APAF‐1, in turn inducing cell cycle
CDC2↓,
CycB↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1↑,
CDK2↓, inhibit CDK2 activity
APAF1↑,
TumCCA↑,
P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
VEGF↓,
Bcl-2↓,
Apoptosis↑,
p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
p‑EGFR↓,
p‑ERK↓,
p‑STAT3↓,
cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
SOD↓,
*BioAv↓, bioavailability of luteolin is very low. Due to the momentous first pass effect, only 4.10% was found to be available from dosage of 50 mg/kg intake of luteolin
*antiOx↓, luteolin classically exhibits antioxidant features
*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
*NO↓,
*GSTs↑, Luteolin may also have a role in protection and enhancement of endogenous antioxidants such as glutathione‐S‐transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
Akt↓,
CDK2↓, inhibit CDK2 activity
BNIP3↑, upregulation of BNIP3 gene
hTERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1↑, Activate beclin 1
TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
NF-kB↓,
IL1↓,
IL6↓,
EMT↓, Suppress EMT essentially notable in cancer metastasis
FAK↓, Block EGFR‐signaling pathway and FAK activity
E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
MDM2↓,
NOTCH↓, Inhibit NOTCH signaling
MAPK↑, Activate MAPK to inhibit tumor growt
Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
N-cadherin↓,
Snail↓,
MMP2↓, negatively regulated MMP2 and TWIST1
Twist↓,
MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
MMP↓,
*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
*MMP↑, Reverse mitochondrial membrane potential dissipation
*Aβ↓, Inhibit Aβ25‐35
*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
Trx1↑, luteolin against human bladder cancer cell line T24 was due to induction cell‐cycle arrest at G2/M, downregulation of p‐S6, suppression of cell survival, upregulation of p21 and TRX1, reduction in ROS levels.
ROS↓,
*NRF2↑, Luteolin reduced renal injury by inhibiting XO activity, modulating uric acid transporters, as well as activating Nrf2 HO‐1/NQO1 antioxidant pathways and renal SIRT1/6 cascade.
NRF2↓, Luteolin exerted anticancer effects in HT29 cells as it inhibits nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway
*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
GutMicro↑, Luteolin was also observed to modulate gut microbiota which reduce the number of tumors in case of colorectal cancer by enhancing the number of health‐related microbiota and reduced the microbiota related to inflammation

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↑,
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

2906- LT,    Luteolin, a flavonoid with potentials for cancer prevention and therapy
- Review, Var, NA
*Inflam↓, anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically
AntiCan↑,
antiOx⇅, With low Fe ion concentrations (< 50 μM), luteolin behaves as an antioxidant while high Fe concentrations (>100 μM) induce luteolin's pro-oxidative effect
Apoptosis↑, induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis.
TumCP↓,
TumMeta↓,
angioG↓,
PI3K↓, , luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP)
Akt↓,
NF-kB↓,
XIAP↓, luteolin inhibits PKC activity, which results in a decrease in the protein level of XIAP by ubiquitination and proteasomal degradation of this anti-apoptotic protein
P53↑, stimulating apoptosis pathways including those that induce the tumor suppressor p53
*ROS↓, Direct evidence showing luteolin as a ROS scavenger was obtained in cell-free systems
*GSTA1↑, Third, luteolin may exert its antioxidant effect by protecting or enhancing endogenous antioxidants such as glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*other↓, luteolin may chelate transition metal ions responsible for the generation of ROS and therefore inhibit lipooxygenase reaction, or suppress nontransition metal-dependent oxidation
ROS↑, Luteolin has been shown to induce ROS in untransformed and cancer cells
Dose↝, It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals
chemoP↑, may act as a chemopreventive agent to protect cells from various forms of oxidant stresses and thus prevent cancer development
NF-kB↓, We found that luteolin-induced oxidative stress causes suppression of the NF-κB pathway while it triggers JNK activation, which potentiates TNF-induced cytotoxicity in lung cancer cells
JNK↑,
p27↑, Table 1
P21↑,
DR5↑,
Casp↑,
Fas↑,
BAX↑,
MAPK↓,
CDK2↓,
IGF-1↓,
PDGF↓,
EGFR↓,
PKCδ↓,
TOP1↓,
TOP2↓,
Bcl-xL↓,
FASN↓,
VEGF↓,
VEGFR2↓,
MMP9↓,
Hif1a↓,
FAK↓,
MMP1↓,
Twist↓,
ERK↓,
P450↓, Recently, it was determined that luteolin potently inhibits human cytochrome P450 (CYP) 1 family enzymes such as CYP1A1, CYP1A2, and CYP1B1, thereby suppressing the mutagenic activation of carcinogens
CYP1A1↓,
CYP1A2↓,
TumCCA↑, Luteolin is able to arrest the cell cycle during the G1 phase in human gastric and prostate cancer, and in melanoma cells


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   Akt↓,2,   p‑Akt↓,2,   angioG↓,1,   AntiCan↑,1,   antiOx⇅,1,   APAF1↑,1,   Apoptosis↑,2,   AR↓,1,   ASC↓,1,   AXL↓,1,   BAX↑,2,   Bcl-2↓,2,   Bcl-xL↓,1,   Beclin-1↑,1,   BioAv↑,1,   BNIP3↑,1,   cachexia↓,1,   cardioP↑,1,   Casp↑,1,   Casp1↓,1,   Casp3↑,2,   Casp8↑,1,   Casp9↑,1,   proCasp9↓,1,   Catalase↓,2,   CD34↓,1,   CDC2↓,1,   Cdc42↓,1,   CDK2↓,3,   CEA↓,1,   cFos↑,1,   chemoP↑,2,   ChemoSen↑,2,   CHOP↑,1,   CLDN1↓,1,   cycA1↑,1,   CycB↓,1,   CYP1A1↓,2,   CYP1A2↓,1,   Cyt‑c↑,2,   Dose↝,1,   DR5↑,3,   E-cadherin↓,1,   E-cadherin↑,1,   EGFR↓,1,   EGFR↑,1,   p‑EGFR↓,1,   p‑eIF2α↑,1,   EMT↓,2,   ERK↓,1,   p‑ERK↓,1,   FAK↓,3,   Fas↑,2,   FasL↑,1,   FASN↓,1,   GPx↓,1,   GSH↓,2,   GSR↓,1,   GSTs↓,1,   GutMicro↑,1,   H3↓,1,   H4↓,1,   HDAC↓,1,   HGF/c-Met↓,1,   Hif1a↓,1,   HO-1↓,1,   hTERT↓,1,   ICAM-1↓,1,   IGF-1↓,1,   IKKα↓,1,   IL1↓,1,   IL2↑,1,   IL6↓,2,   ITGB1↓,1,   JNK↑,1,   p‑JNK↑,1,   LC3II↑,1,   MAPK↓,2,   MAPK↑,1,   MDM2↓,1,   p‑MDM2↓,1,   MET↓,1,   p‑MET↓,1,   MMP↓,1,   MMP1↓,1,   MMP2↓,2,   MMP9↓,2,   mTOR↓,1,   N-cadherin↓,2,   NF-kB↓,4,   NLRP3↓,1,   NOTCH↓,1,   NOTCH1↓,1,   NQO1↓,1,   NRF2↓,2,   NSE↓,1,   P21↑,1,   p27↑,1,   p‑p38↑,1,   P450↓,1,   P53↑,2,   p‑p65↓,1,   PARP↑,1,   PCNA↓,1,   PD-1↓,1,   PDGF↓,1,   PI3K↓,2,   p‑PI3K↓,1,   PKCδ↓,1,   PTEN↓,1,   Rac1↓,1,   RadioS↑,1,   Rho↓,1,   ROS↓,1,   ROS↑,3,   SIRT1↓,1,   Snail↓,2,   SOD↓,2,   SOD2↓,1,   p‑Src↓,1,   STAT3↓,1,   p‑STAT3↓,1,   p‑STAT6↓,1,   TNF-α↓,1,   TOP1↓,1,   TOP2↓,1,   Trx1↑,1,   TumCCA↑,2,   TumCP↓,1,   TumMeta↓,1,   Twist↓,2,   Tyro3↓,1,   VEGF↓,3,   VEGFR2↓,1,   Vim↓,1,   Vim↑,1,   VitC↓,1,   VitE↓,1,   XIAP↓,2,   ZO-1↑,1,   β-catenin/ZEB1↓,1,  
Total Targets: 142

Results for Effect on Normal Cells:
AChE↓,1,   antiOx↓,1,   Aβ↓,1,   BBB↑,1,   BioAv↓,1,   Casp3↓,1,   Catalase↑,3,   eff↑,1,   GPx↑,1,   GSH↑,1,   GSR↑,2,   GSTA1↑,1,   GSTs↑,2,   Half-Life↝,1,   IL10↑,1,   IL1β↓,1,   Inflam↓,1,   lipid-P↓,2,   MMP↑,1,   neuroP↑,1,   NO↓,1,   NRF2↑,1,   other↓,1,   ROS↓,2,   SOD↑,3,   TNF-α↓,1,  
Total Targets: 26

Scientific Paper Hit Count for: FAK, FAK signaling
3 Luteolin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:118  Target#:110  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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