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


cMyc, cellular-MYC oncogene: Click to Expand ⟱
Source:
Type: oncogene
The MYC proto-oncogenes are among the most commonly activated proteins in human cancer. The oncogene c-myc, which is frequently over-expressed in cancer cells, is involved in the transactivation of most of the glycolytic enzymes including lactate dehydrogenase A (LDHA) and the glucose transporter GLUT1 [51,52]. Thus, c-myc activation is a likely candidate to promote the enhanced glucose uptake and lactate release in the proliferating cancer cell. The c-Myc oncogene is a ‘master regulator’ of both cellular growth and metabolism in transformed cells.
-C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A

Inhibitors (downregulate):
Curcumin
Resveratrol: downregulate c-Myc expression.
Epigallocatechin Gallate (EGCG)
Quercetin
Berberine: decrease c-Myc expression and repress its transcriptional activity.
Scientific Papers found: Click to Expand⟱
2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
ROS↑, induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells.
TumCCA↑,
TumCP↓,
angioG↓,
ER Stress↑, Luteolin induces mitochondrial dysfunction and activates the endoplasmic reticulum stress response in glioblastoma cells, which triggers the generation of intracellular reactive oxygen species (ROS)
mtDam↑,
PERK↑, activate the expression of stress-related proteins by mediating the phosphorylation of PERK, ATF4, eIF2α, and cleaved-caspase 12.
ATF4↑,
eIF2α↑,
cl‑Casp12↑,
EMT↓, Luteolin is known to reverse epithelial-to-mesenchymal transition (EMT), which is associated with the cancer cell progression and metastasis.
E-cadherin↑, upregulating the biomarker E-cadherin expression, followed by a significant downregulation of the N-cadherin and vimentin expression
N-cadherin↓,
Vim↓,
*neuroP↑, Furthermore, luteolin holds potential to improve the spinal damage and brain trauma caused by 1-methyl-4-phenylpyridinium due to its excellent neuroprotective properties.
NF-kB↓, downregulation and suppression of cellular pathways such as nuclear factor kappa B (NF-kB), phosphatidylinositol 3’-kinase (PI3K)/Akt, and X-linked inhibitor of apoptosis protein (XIAP)
PI3K↓,
Akt↑,
XIAP↓,
MMP↓, Furthermore, the membrane action potential of mitochondria depletes in the presence of luteolin, Ca2+ levels and Bax expression upregulate, the levels of caspase-3 and caspase-9 increase, while the downregulation of Bcl-2
Ca+2↑,
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
Cyt‑c↑, cause the cytosolic release of cytochrome c from mitochondria
IronCh↑, Luteolin serves as a good metal-chelating agent owing to the presence of dihydroxyl substituents on the aromatic ring framework
SOD↓, luteolin further triggered an early phase accumulation of ROS due to the suppression of the activity of cellular superoxide dismutase.
*ROS↓, Luteolin reportedly demonstrated an optimal 43.7% inhibition of the accumulation of ROS, 24.5% decrease in malondialdehyde levels, and 38.7% lowering of lactate dehydrogenase levels at a concentration of 30 µM
*LDHA↑,
*SOD↑, expression of superoxide dismutase ameliorated by 73.7%, while the activity of glutathione improved by 72.3% at the same concentration of luteolin
*GSH↑,
*BioAv↓, Poor bioavailability of luteolin limits its optimal therapeutic efficacy and bioactivity
Telomerase↓, MDA-MB-231 cells with luteolin led to dose dependent arrest of cell cycle in S phase by reducing the levels of telomerase and by inhibiting the phosphorylation of NF-kB inhibitor α along with its target gene c-Myc
cMyc↓,
hTERT↓, These events led to the suppression of the expression of human telomerase reverse transcriptase (hTERT) encoding for the catalytic subunit of telomerase
DR5↑, luteolin upregulated the expression of caspase cascades and death receptors, including DR5
Fas↑, expression of proapoptotic genes such as FAS, FADD, BAX, BAD, BOK, BID, TRADD upregulates, while the anti-apoptotic genes NAIP, BCL-2, and MCL-1 experience downregulation.
FADD↑,
BAD↑,
BOK↑,
BID↑,
NAIP↓,
Mcl-1↓,
CDK2↓, expression of cell cycle regulatory genes CDK2, CDKN2B, CCNE2, CDKN1A, and CDK4 decreased on incubation with luteolin
CDK4↓,
MAPK↓, expression of MAPK1, MAPK3, MAP3K5, MAPK14, PIK3C2A, PIK3C2B, AKT1, AKT2, and ELK1 downregulated
AKT1↓,
Akt2↓,
*Beclin-1↓, luteolin led to downregulation of the expression of hypoxia-inducible factor-1α and autophagy-associated proteins, Beclin 1, and LC3
Hif1a↓,
LC3II↑, LC3-II is upregulated following the luteolin treatment in p53 wild type HepG2 cells i
Beclin-1↑, Luteolin treatment reportedly increased the number of intracellular autophagosomes, as indicated by an increased expression of Beclin 1, and conversion of LC3B-I to LC3B-II in hepatocellular carcinoma SMMC-7721 cells.

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↓,
CycB↓,
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↓,
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↓,
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↓,
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↓,

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
Half-Life↝, However, after oral administration, luteolin showed relatively rapid absorption and slow elimination in rats, with a tmax (time to reach peak plasma level) of approximately 1.02 h and a t1/2 (elimination half-life) of 4.94 h, indicating that luteolin
TumCCA↑, luteolin could promote cell cycle arrest and apoptosis in HuH-7 cells
AKT1↓, Dramatic downregulation of components downstream of the AKT1-ASK2-ATF2 pathway (CycD, BCL2, CycA, etc.), the AKT1-NF-κB pathway (BCL-XL and MIP2) and the AKT1-GSK3β-β-catenin pathway (c-Myc and CCND1)
ATF2↓,
NF-kB↓,
GSK‐3β↓,
cMyc↓,
GSTs↓, expression change of NQO-1, GSTs, and TRXR1 indicated the increase in ROS
TrxR1↓,
ROS↑,

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
AEG1↓,1,   Akt↓,1,   Akt↑,1,   AKT1↓,2,   Akt2↓,1,   angioG↓,2,   Apoptosis↑,1,   AR↓,1,   ATF2↓,1,   ATF4↑,1,   BAD↑,1,   BAX↑,2,   Bcl-2↓,1,   Beclin-1↑,1,   BID↑,1,   BOK↑,1,   Ca+2↑,2,   cl‑Casp12↑,1,   Casp3↑,1,   cl‑Casp3↑,1,   cl‑Casp8↑,1,   Casp9↑,1,   cl‑Casp9↑,1,   CDC2↓,1,   CDK2↓,2,   CDK4↓,1,   ChemoSen↓,1,   ChemoSen↑,1,   cMyc↓,3,   p‑cMyc↑,1,   COX2↓,1,   CXCR4↓,1,   CycB↓,1,   cycD1↓,2,   Cyt‑c↑,1,   DNAdam↑,1,   DR5↑,2,   E-cadherin↑,2,   eIF2α↑,1,   EMT↓,2,   ER Stress↑,2,   ERK↓,1,   FADD↑,1,   Fas↑,1,   GSK‐3β↓,1,   p‑GSK‐3β↓,1,   GSTs↓,1,   Half-Life↝,1,   Hif1a↓,1,   HO-1↓,1,   hTERT↓,2,   IFN-γ↓,1,   iNOS↓,1,   IronCh↑,1,   JNK↑,1,   LC3B-II↑,1,   LC3II↑,1,   MAPK↓,1,   Mcl-1↓,1,   MDM2↓,1,   MDR1↓,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   mtDam↑,1,   N-cadherin↓,2,   NAIP↓,1,   NF-kB↓,3,   p‑NF-kB↑,1,   NICD↓,1,   NOTCH1↓,1,   NRF2↓,1,   NRF2↑,1,   P21↑,1,   P53↑,1,   cl‑PARP↑,1,   PERK↑,1,   PI3K↓,2,   RadioS↑,1,   RAS↓,1,   ROS↑,3,   SOD↓,1,   survivin↓,1,   TAZ↓,1,   Telomerase↓,2,   TIMP1↑,1,   TIMP2↑,1,   TrxR1↓,1,   TumAuto↑,1,   TumCCA↑,3,   TumCMig↓,1,   TumCP↓,2,   VEGF↓,1,   VEGFR2↓,1,   Vim↓,1,   Wnt↓,2,   XIAP↓,1,   YAP/TEAD↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 99

Results for Effect on Normal Cells:
antiOx↑,1,   Beclin-1↓,1,   BioAv↓,2,   BioAv↑,1,   GSH↑,1,   IronCh↑,1,   LDHA↑,1,   neuroP↑,1,   ROS↓,1,   SOD↑,1,   toxicity↓,1,  
Total Targets: 11

Scientific Paper Hit Count for: cMyc, cellular-MYC oncogene
4 Luteolin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:118  Target#:35  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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