HO-1 Cancer Research Results

HO-1, HMOX1: Click to Expand ⟱

Source:

Type:

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

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

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

-Curcumin Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.

Scientific Papers found: Click to Expand⟱

256-

AL,

doxoR,

Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

NRF2↓,
HO-1↓,
p‑Akt↓,

1235-

ALA,

Cisplatin,

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway

in-vitro,

Nor,

HEI-OC1

20μM cisplatin, 0-2mM(ALA)

ex-vivo,

NA,

ROS↑, production of reactive oxygen species (ROS) by cisplatin is one of the major mechanisms of cisplatin-induced cytotoxicity
HO-1↓, due to Cisplatin only
*toxicity↓, LA was safe at concentrations up to 0.5 mM in HEI-OC1 cells (normal)
chemoP↑, had a protective effect against cisplatin-induced cytotoxicity
*ROS↓, Intracellular ROS production in HEI-OC1(normal) cells was rapidly increased by cisplatin for up to 48 h. However, treatment with LA significantly reduced the production of ROS
*HO-1↑, and increased the expression of the antioxidant proteins HO-1 and SOD1
*SOD1↑,
*NRF2↑, antioxidant activity of LA was through the activation of the NRF2/HO-1 antioxidant pathway

4992-

ART/DHA,

Dihydroartemisinin Increases the Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via the Nrf2/HO-1 Anti-Oxidant Signaling Pathway

in-vitro,

AML,

HL-60

Apoptosis↑, The combination of Ara-C and DHA synergistically promoted the apoptosis and differentiation of HL-60 cells
Diff↑,
ROS↓, Mechanistically, synergistic cytotoxic effects of Ara-C/DHA on HL-60 cells may be mediated by decreasing intracellular ROS levels
HO-1↓, However, DHA only caused the down-regulation of HO-1, whereas the expression level of nuclear Nrf2 was unaffected.
NRF2∅,

4993-

ART/DHA,

Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway

vitro+vivo,

GC,

Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
HO-1↓,
PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
Akt↓,
TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

2296-

Ba,

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms

Review,

Var,

CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

5536-

BBM,

Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers

Review,

Var,

JAK↝, In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers.
STAT3↓, Berbamine physically interacted with STAT3 and inhibited its activation [8].
p‑CaMKII ↓, An orally administered, bioactive small molecule analog of berbamine, tosyl chloride-berbamine (TCB), considerably reduced phosphorylated levels of CaMKIIγ
TGF-β↑, berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression.
Smad1↑,
ChemoSen↑, Berbamine enhanced the chemosensitivity of gefitinib against PANC-1 and MIA PaCa-2 cancer cells [8].
RadioS↑, Moreover, berbamine and radiation effectively induced a regression of the tumors in mice subcutaneously injected with FaDu cells [10].
TumCI↓, berbamine-GMO-TPGS nanoparticles showed superior cellular toxicity, as well as an inhibition of migration and invasion in metastatic breast cancer MDA-MB-231,
TumCMig↓,
ROS↑, Berbamine increased the intracellular ROS levels via the downregulation of antioxidative genes such as NRF2, SOD2, GPX-1 and HO-1.
NRF2↓,
SOD2↓,
GPx1↓,
HO-1↓,

5551-

BBM,

Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis

vitro+vivo,

Bladder,

tumCV↓, our results showed that berbamine inhibited cell viability, colony formation, and proliferation.
TumCP↓,
TumCCA↑, Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression
P21↑,
p27↑,
cycD1/CCND1↓, as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression.
cycA1/CCNA1↓,
CDK2↓,
EMT↓, In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis.
TumMeta↓,
p65↓, Mechanistically, the expression of P65, P-P65, and P-IκBα was decreased upon berbamine treatment
p‑p65↓,
IKKα↓,
NF-kB↑, berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-κB pathway.
ROS↑, More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1.
NRF2↓,
HO-1↓,
SOD2↓,
GPx1↓,
Bax:Bcl2↑, increase in the ratio of Bax/Bcl-2.
TumVol↓, berbamine successfully inhibited tumor growth and blocked the NF-κB pathway in our xenograft model

1392-

BBR,

Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress

in-vitro,

GC,

AGS

2.5, 5, 10, 20, 40 µM

in-vitro,

GC,

MKN45

TumCG↓,
TumCMig↓,
ROS↑, intracellular
MDA↑, intracellular
SOD↓, intracellular
NRF2↓,
HO-1↓,
Hif1a↓,
EMT↓,
Snail↓,
Vim↓,

1390-

BBR,

Rad,

Berberine Inhibited Radioresistant Effects and Enhanced Anti-Tumor Effects in the Irradiated-Human Prostate Cancer Cells

in-vitro,

Pca,

PC3

RadioS↑, cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone
Apoptosis↑,
ROS↑, ROS generation was elevated by berberine with or without irradiation.
eff↑, antioxidant NAC inhibited berberine and radiation-induced cell death.
BAX↑,
Casp3↑,
P53↑,
p38↑,
JNK↑,
Bcl-2↓,
ERK↓,
HO-1↓,

2756-

BetA,

Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway

in-vitro,

HCC,

HUH7

10 μM was selected as a low dose (BETL group), 20 μM as a medium dose (BETM group) and 40 μM as a high dose (BETH group)

in-vitro,

HCC,

H1299

TumCP↓, betulinic acid could suppress proliferation and migration of hepatoma cells, raised ROS level and inhibited antioxidation level in cells
ROS↑,
antiOx↓,
TumCG↓, These findings indicate that betulinic acid has the capacity to significantly impede hepatoma cells growth and migration
TumCMig↓,
NRF2↓, The expression of antioxidant proteins Nrf2, GPX4 and HO-1 was also considerably lower in the BETM and BETH groups than in the Control group
GPx4↓,
HO-1↓,
NCOA4↑, suggesting that betulinic acid activates ferritinophagy by boosting NCOA4 expression and FTH1 degradation.
FTH1↓, betulinic acid groups (10 mg/kg, 20 mg/kg, and 40 mg/kg) greatly boosted LC3II and NCOA4 expressions and suppressed FTH1
Ferritin↑, In summation, betulinic acid decreases antioxidation in tumour tissues from nude mice, inhibits ferritin expression, enhances the expression of ferritinophagy-associated protein, activates ferritinophagy, and initiates ferroptosis in tumour cells.
Ferroptosis↑,
GSH↓, In comparison to the Control group, the betulinic acid groups (10 mg/kg, 20 mg/kg and 40 mg/kg) reduced dramatically GSH and hydroxyl radical inhibition capacity in serum, considerably increased serum Fe2+), and decreased dramatically serum MDA
MDA↓,

5690-

BJ,

BRU,

Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica

Review,

Var,

NRF2↓, Brusatol is a potent Nrf2 inhibitor for future cancer treatment.
TumCG↓, Brusatol exhibits significant tumor inhibition in multiple cancers.
ChemoSen↑, also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents
ROS↑, Graphical Abstract
NF-kB↓,
Akt↓,
mTOR↓,
TumCCA↑,
Apoptosis↑,
PARP↑,
Casp↑,
P53↓,
Bcl-2↓,
PI3K↓,
JAK2↓,
EMT↓,
p27↑,
ROCK1↓,
MMP2↓,
MMP9↓,
NRF2↓, which is the reason why brusatol is called an Nrf2 inhibitor [15]. Brusatol is a potent Nrf2 inhibitor
AntiTum↑, Brusatol shows significant antitumor effects in vitro and in vivo
HO-1↓, Moreover, brusatol inhibited the expression of Nrf2 downstream genes, such as HO-1 [19], [31], [32], NQO1 [43], [44], VEGF [45], and AKR1C1 [46].
NQO1↓,
VEGF↓,
MRP1↓, brusatol reduced both the mRNA and protein levels of NQO1, HO-1, MDR1, and MRP5
RadioS↑, Improvement of sensitivity to radiotherapy and phototherapy
PhotoS↑,
toxicity↝, the toxicity of brusatol is a problem that can not be ignored.

5680-

BML,

Anticancer properties of bromelain: State-of-the-art and recent trends

Review,

Var,

*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju

6017-

CGA,

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment

Review,

Var,

AntiCan↑, Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms.
*chemoP↑, CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively.
TNF-α↓, CGA reduces inflammation levels in renal tissues by down-regulating tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2),
COX2↓,
IL6↓, Moreover, CGA exhibits a protective effect against 5-FU-induced ovarian tissue damage, reducing Interleukin 6 (IL-6) levels;
eff↑, CGA suppresses the expression of Programmed Cell Death Ligand 1 (PD-L1) on cancer cells, boosting the antitumor effect of the anti-PD-1 antibody and enhancing anticancer immunotherapy
PD-L1↓,
*cognitive↓, CGA, have shown promise in preventing cognitive dysfunction and suppressing amyloid β plaques
*Aβ↓,
*TAC↑, hyperlipidemic patients who ingested 200 mL of Mate tea (12.5 mg/mL) daily experienced a significant increase in serum total antioxidant status and the enzymatic activity of superoxide dismutase (SOD),
*SOD↑,
*eff↑, In blueberry jam production, the high-temperature processing of blueberries with sucrose promoted the formation of 11 CGA derivatives
*eff↑, roasting process (170 to 200 °C/10 to 30 min) of coffee beans promotes CGA transformation to four chlorogenic acid lactones
ChemoSen↑, CGA was found to increase the sensitivity of hepatocellular carcinoma cells to 5-FU treatment
tumCV↓, CGA was shown to collaborate by significantly reducing cell viability and growth through induction of apoptosis, attributed to inhibition of extracellular signal-regulated kinases (ERKs)
Apoptosis↑,
ERK↓,
chemoP↑, Protective Role of Chlorogenic Acid against Toxicity Induced by Chemotherapy
*GPx↑, figure4
*GSTs↑,
*GSH↑,
*SOD↑,
*Catalase↑,
*ROS↓,
*lipid-P↓,
*MDA↓,
*Casp3↓,
*HO-1↓,
cardioP↑, reported the cardioprotective effect of CGA against doxorubicin-induced cardiotoxicity in female Swiss albino mice.
radioP↑, The radioprotective potential of CGA against γ-radiation-induced chromosomal damage in male albino Swiss mice was initially demonstrated in 1993.

6010-

CGA,

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

Review,

Nor,

*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

2590-

CHr,

Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell lines via mediating the ERK/Nrf2 signaling pathway

in-vitro,

GBM,

T98G

in-vitro,

GBM,

U251

in-vitro,

GBM,

U87MG

TumCP↓, Chrysin inhibited the proliferation, migration, and invasion capacity of glioblastoma cells in dose- and time-dependent manners.
TumCMig↓,
TumCI↓,
NRF2↓, chrysin deactivated the Nrf2 signaling pathway by decreasing the translocation of Nrf2 into the nucleus
HO-1↓, suppressing the expression of hemeoxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1
NADPH↓,
ERK↓, Chrysin treatment downregulates the Nrf2 pathway via inhibition of ERK signaling

2591-

CHr,

doxoR,

Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway

in-vitro,

HCC,

Bel-7402

NRF2↓, chrysin is a potent Nrf2 inhibitor which sensitizes BEL-7402/ADM cells to ADM
ChemoSen↑, chrysin may be an effective adjuvant sensitizer to reduce anticancer drug resistance by down-regulating Nrf2 signaling pathway.
HO-1↓, Consequently, expression of Nrf2-downstream genes HO-1, AKR1B10, and MRP5 were reduced

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

1410-

CUR,

Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway

vitro+vivo,

OS,

MG63

tumCV↓,
Apoptosis↑,
TumCG↓,
NRF2↓, after treatment with curcumin, Nrf2 and GPX4 levels were significantly decreased
GPx4↓,
HO-1↓,
xCT↓, SLC7A11
ROS↑, our results revealed that after treatment with curcumin, ROS and MDA levels were significantly increased while GSH levels were decreased
MDA↑,
GSH↓,

1863-

dietFMD,

Chemo,

Effect of fasting on cancer: A narrative review of scientific evidence

Review,

Var,

eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

1847-

dietFMD,

VitC,

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers

in-vitro,

PC,

PANC1

vitamin C (≥0.3 mM)

TumCG↓, Fasting-mimicking diets delay tumor progression
ChemoSen↑, sensitize a wide range of tumors to chemotherapy
eff↑, vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1
HO-1↓, FMD reverses the effect of vitamin C on HO-1(downregulating HO-1)
Ferritin↓,
Iron↑, consequently increasing reactive iron, oxygen species, and cell death
ROS↑, Vitamin C’s pro-oxidant action is strictly dependent on metal-ion redox chemistry. In particular, free iron was shown to be a key player in vitamin C-induced cytotoxic effects
TumCD↑,
IGF-1↓, effects on the insulin-like growth factor 1 (IGF-1)
eff↓, When cancer cells were grown under STS conditions before and during treatment, vitamin C-mediated toxicity was strongly enhanced
eff↓, Conversely, KRAS-wild-type CRC (SW48, HT29), prostate cancer (PC-3), ovarian cancer (COV362) cell lines and a normal colon cell line (CCD841CoN) were resistant to vitamin C when used both as a single agent and in combination with STS

1846-

dietFMD,

VitC,

A fasting-mimicking diet and vitamin C: turning anti-aging strategies against cancer

Study,

Var,

TumCG↓, FMDs delay tumor progression
ChemoSen↑, potentiate chemotherapy efficacy
ChemoSideEff↓, while protecting healthy tissues from chemo-associated side effects in different cancer models
ROS↑, presence of metals, and particularly iron, high dose of vitamin C exerts a pro-oxidant action by generating hydrogen peroxide and hydroxyl radicals via Fenton chemistry
Fenton↑,
H2O2↑,
eff↑, we show that FMD cycles potentiate high-dose vitamin C anti-cancer effects in a range of cancer types
HO-1↓, KRAS-mutant cancer cells respond to vitamin C treatment by up-regulating HO-1, and consequently limiting vitamin C pro-oxidant action. FMD is able to revert HO-1 up-regulation
DNAdam↑, increase in free reactive iron and oxygen species causing DNA damage and cell death
eff↑, we found that the nontoxic FMD + vitamin C combination therapy is as effective as oxaliplatin + vitamin C in delaying tumor progression while the triple FMD, vitamin C and chemotherapy combination treatment is the most effective.

1859-

dietFMD,

Chemo,

Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity

in-vitro,

BC,

4T1

in-vivo,

Melanoma,

B16-BL6

mice

CLP↑, combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells (CLP) and cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma
CD8+↑,
TumCG↓,
HO-1↓, In breast tumors, this effect is partially mediated by the down-regulation of the stress-responsive enzyme heme oxygenase-1 (HO-1)
TILs↑, FMD in combination with doxorubicin (DXR) promotes accumulation of tumor-infiltrating lymphocytes (TILs) in the tumor bed

1626-

dietSTF,

dietFMD,

When less may be more: calorie restriction and response to cancer therapy

Review,

Var,

CRM↑,
ChemoSen↑, CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies.
RadioS↑,
eff↑, CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies.
eff↑, Intermittent fasting has been shown to enhance treatment with both chemotherapy and radiation therapy.
IGF-1↓, Exposure to an energy restricted diet results in reduced systemic glucose and growth factors such as IGF-1
TumCG↓, reduction of IGF-1 levels in CR results in decreased tumor growth and progression
AMPK↑, CR also induces activation of AMP-activated protein kinase (AMPK), (working in opposition to IGF-1)
eff↑, Recent research in our lab showed that combining autophagy inhibition with a CR regimen reduced tumor growth more than either treatment alone [20].
ChemoSen↑, Short-term fasting has been shown to improve chemotherapeutic treatment with etoposide [40], mitoxantrone, oxaliplatin [41], cisplatin, cyclophosphamide, and doxorubicin [42] in transgenic and transplant mouse models
RadioS↑, Alternate day fasting has also been shown to improve the radiosensitivity of mammary tumors in mice
ROS↑, improve the radiosensitivity: likely due to enhanced oxidative stress and DNA damage during short-term fasting on cancer cells.
DNAdam↑,
eff↑, fasting-mimicking diet, in which mice are fed the same amount of food as control mice, albeit with a severely reduced caloric density, showed a similar reduction in tumor growth as short-term starvation
HO-1↓, fasting-mimicking diet were associated with increased autophagy in the cancer cells and reduced heme oxygenase-1 (HO-1) in the microenvironment

4990-

Dipy,

Characterization of dipyridamole as a novel ferroptosis inhibitor and its therapeutic potential in acute respiratory distress syndrome management

in-vivo,

Nor,

*Ferroptosis↓, These findings provide compelling evidence that DIPY inhibits ferroptosis in pulmonary epithelial and endothelial cells by modulating the SOD1/CREB1/HMOX1 signaling axis and suggest DIPY as a promising therapeutic strategy for ARDS treatment.
*HO-1↓, effectively mitigated ferroptosis and pulmonary damage in both mouse models and hAOs, primarily by downregulating heme oxygenase 1 (HMOX1).
SOD1↑, DIPY binds to and activates superoxide dismutase 1 (SOD1), which in turn inhibits the CREB1/HMOX1 pathway, thereby suppressing ferroptosis.

5007-

DSF,

Cu,

Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma

vitro+vivo,

Oral,

AntiTum↑, Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers.
TumCP↓, DSF/Cu reduced the proliferation and clonogenicity of OSCC cells.
Ferroptosis↑, DSF/Cu also induced ferroptosis
Iron↑, Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death.
lipid-P↑,
NRF2↓, DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1.
HO-1↓,

1605-

EA,

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Review,

Var,

*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1621-

EA,

The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art

Review,

Var,

AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

3214-

EGCG,

EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway

in-vitro,

Nor,

MRC-5

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HEK293

in-vitro,

BC,

MDA-MB-231

in-vitro,

CRC,

HCT116

mTOR↓, In contrast, EGCG treatment in HeLa cells led to AMPK-induced mTOR inactivation
AMPK↑, via AMPK activation,
selectivity↑, EGCG was previously reported to differentially induce ROS production in normal and cancer cells, resulting in the preferential perturbation of the redox homeostasis of cancer cells via increased ROS levels, especially H2O2, in cancer cells
ROS↑,
selectivity↑, EGCG-induced selective death of cancer cells is accomplished by the positive and negative regulation of the p62-KEAP1-NRF2-HO-1 antioxidant survival pathway between normal cells and cancer cells, respectively,
HO-1↓, HO-1 expression decreased significantly with increasing EGCG concentration in all six different cancer cells
*NRF2↑, According to our findings, EGCG increased the protein level of NRF2 in normal cells but decreased them in cancer cells even though its mRNA levels were more or less equal in both cell types
NRF2↓,
*HO-1↑, upregulates HO-1 through the prolonged stability of NRF2 in MRC5 cells, whereas it downregulates HO-1 through the increased degradation of NRF2 by ubiquitination in HeLa and HCT116 cells.

2514-

H2,

Hydrogen: A Novel Option in Human Disease Treatment

Review,

NA,

*Inflam↓, Anti-Inflammatory Effect of H2
*IL1β↓, decrease the overexpression of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α
*IL6↓,
*IL8↓,
*IL10↓,
*TNF-α↓,
*ROS↓, . H2 can also downregulate ROS directly or as a regulator of a gas-mediated signal.
*HO-1↓, H2 can enhance the expression of the heme oxygenase-1 (HO-1) antioxidant by activating nuclear factor erythroid 2-related factor 2 (Nrf-2), an upstream regulating molecule of HO-1
*NRF2↑,
*ER Stress↓, hydrogen inhalation significantly reduced the ER stress-related protein and alleviated tissue damage in myocardial I/R injury a
H2O2↑, H2-induced ROS production can also be observed in cancer cells.

1633-

HCA,

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway

in-vivo,

NA,

mice, Lung ischemia-reperfusion injury (LIRI)

in-vitro,

Nor,

HUVECs

*other↓, HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion
*Inflam↓,
*MDA↓, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels
*ROS↓,
*Iron↓, while decreasing iron content and increasing superoxide dismutase (SOD)
*SOD↓,
*Hif1a↓, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro.
*HO-1↓,

2894-

HNK,

Pharmacological features, health benefits and clinical implications of honokiol

Review,

Var,

Review,

AD,

*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp↓, The expres- sion of P-gp at mRNA and protein levels is reduced in HNK treatment on human MDR and MCF-7/ADR breast cancer cell lines

2587-

LT,

Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs

in-vitro,

Lung,

A549

1-20uM

NRF2↓, luteolin elicited a dramatic reduction in Nrf2 at both the mRNA and the protein levels, leading to decreased Nrf2 binding to AREs, down-regulation of ARE-driven genes, and depletion of reduced glutathione.
GSH↓,
ChemoSen↑, luteolin significantly sensitized A549 cells to the anticancer drugs oxaliplatin, bleomycin, and doxorubicin.
HO-1↓, ↓HO-1

2588-

LT,

Chemo,

Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway

in-vitro,

CRC,

HCT116

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

2589-

LT,

Chemo,

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

in-vitro,

BC,

MDA-MB-231

1 to 2 μM) of luteolin for 48 h

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

2927-

LT,

Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells

in-vitro,

Cerv,

HeLa

 5, 10, and 20 µM of luteolin for 48 h

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

2914-

LT,

Therapeutic Potential of Luteolin on Cancer

Review,

Var,

3–50 µM in vitro

*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2↓,
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/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
MDR1↓,

2919-

LT,

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

Review,

Var,

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

1204-

MET,

Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

MDA↑,
ROS↑,
Iron↑, iron ions
GSH↓,
T-SOD↓,
Catalase↓,
GPx4↓,
xCT↓,
NRF2↓,
HO-1↓,

1770-

PG,

Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation

in-vitro,

Lung,

antiOx↑, Propyl gallate (PG) is a synthetic phenolic compound that possess a potent anti-oxidant and anti-inflammatory activities.
Inflam↓,
HO-1↓, PG dose-dependently diminished HO-1 protein levels without changing its mRNA levels and consequently decreased HO-1 activity
eff↑, PG also significantly enhanced the sensitivity of NSCLC cells to cisplatin-induced apoptosis, and this effect was attenuated by overexpression of HO-1.
ChemoSen↑, PG exerted its chemosensitization effect by down-regulating HO-1 protein expression through a TRC8 (translocation in renal carcinoma, chromosome 8)-mediated ubiquitin-proteasome pathway

3077-

RES,

Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways

in-vitro,

Chon,

HTB94

MMP2↓, We found that resveratrol significantly inhibited MMP-2 and MMP-9, and induced the expression of type II collagen and sex-determining region Y-box (SOX)-9 and the production of sulfated proteoglycans in HTB94 chondrosarcoma cells.
MMP9↓,
SOX9↑,
MMPs↓,
p‑p38↑, Phosphorylation of p38 was increased and phosphorylation of c-Jun N-terminal kinase (JNK) was inhibited by resveratrol
p‑JNK↓,
NF-kB↓, Moreover, resveratrol reduced lung adenocarcinoma cell metastasis by suppressing heme oxygenase (HO)-1-mediated nuclear factor (NF)-κB pathway activation and subsequently downregulated the expression of MMPs.
HO-1↓, Resveratrol inhibited the transcription-activator function of HO-1 and subsequently MMP-2 and MMP-9 expression in human lung cancer cells as well.

4908-

Sal,

Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling

in-vitro,

Pca,

PC3

0, 2, 5, 10, 20 and 50 µM

in-vitro,

Pca,

DU145

tumCV↓, salinomycin inhibited the viability and induced the apoptosis of PC-3 and DU145 cells in a dose-dependent manner
ROS↑, salinomycin increased the production of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and the lipid peroxidation.
lipid-P↑,
UPR↑, salinomycin induced the activation of unfolded protein response and endoplasmic reticulum stress in DU145 and PC-3 cells
ER Stress↑,
NRF2↓, salinomycin significantly downregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone dehydrogenase 1
NADPH↓,
HO-1↓,
SOD↓, and decreased the activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in PC-3 and DU145 cells.
Catalase↓,
GPx↓,
eff↓, Nrf2 activator, tert-butylhydroquinone, significantly reversed the therapeutic effects of salinomycin by stimulating the Nrf2 pathway and increasing the activity of antioxidant enzymes.
TumCP↓, proliferation of PC-3 and DU145 cells was significantly decreased following treatment with salinomycin (2-50 µM

4726-

Se,

Oxy,

Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma

in-vivo,

HCC,

tumor-bearing mice

eff↝, Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory.
NRF2↓, We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2
p‑p38↑, and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis
Apoptosis↑,
eff↑, These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways
TumVol↓, The results showed that hyperoxia could improve the efficacy of Na2SeO3 and CysSeSeCys in the treatment of HCC, enhance the death rate of HepG2 cells, and further reduce the tumor volume in mice
other↝, These results also suggest that the anticancer mechanism of selenium compounds may be different in different oxygen environments.
toxicity↓, staining results of the liver and kidney of mice showed that the selenium compound combined with oxygen therapy did not show toxicity or side effects on normal organs
Dose↝, therapeutic effect reached the level of the 5 mg/kg selenium compound treatment group
NRF2↝, The results showed that in the 1 % O2 environment, the two selenium compounds promoted the expression of Nrf2, and the Nrf2 level gradually decreased with increasing oxygen concentration.
HO-1↓, The expression of HO-1, CAT and SOD also showed a decreasing trend with increasing oxygen concentration
Catalase↓,
SOD↓,
e-pH↓, The results showed that the extracellular pH value decreased after treatment with selenium compounds for 48 h
pH∅, However, there was no significant change in extracellular pH value in the selenium compound treatment group compared with the oxygen alone group
MAPK↑, Selenium combined with oxygen therapy accelerates cell apoptosis by activating the MAPK signaling pathway
eff↑, In summary, oxygen can significantly enhance the antihepatocellular carcinoma effect of selenium compounds

2132-

TQ,

Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis

in-vivo,

Nor,

10 and 20 mg/kg p.o.) for 28 days

Lung fibrosis was induced in rats

*Weight∅, BM administration resulted in a significant weight loss, which was ameliorated by TQ treatment.
*antiOx↑, BMILF was associated with a reduction in the antioxidant mechanisms and increased lipid peroxidation (abnormalities were diminished with TQ treatment)
*lipid-P↓,
*MMP7↓, elevated levels of inflammatory cytokines, MMP-7 expression, apoptotic markers (caspase 3, Bax, and Bcl-2), and fibrotic changes including TGF-β and hydroxyproline levels in lung tissues were evident. These abnormalities were diminished with TQ
*Casp3↓,
*BAX↓,
*TGF-β↓,
*Diff↑, differential cell count in BALF was significantly improved in rats treated with TQ
*NRF2↓, TQ also produced a dose-dependent reduction in the expressions of Nrf2, Ho-1 and TGF-β. (ai:once TQ reduces oxidative damage, the demand for high Nrf2 activity drops)
*HO-1↓,
*NF-kB↓, NF-jB protein expression has been significantly and dose dependently decreased in TQ treated groups (10 and 20 mg/kg bw)
*IκB↑, IkBa has been significantly and dose dependently increase in TQ treated groups (10 and 20 mg/kg bw).

3108-

VitC,

QC,

The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells

in-vitro,

BC,

MDA-MB-231

in-vitro,

Lung,

A549

NRF2↓, significant decrease in the expression of Nrf2 mRNA and protein levels following the treatment of breast cancer cells with VC and Q
HO-1↓, In the MDA-MB 231 and MCF-7 cell lines, HO1 was significantly suppressed following treatment with VC and Q
ROS↑, It was demonstrated that ROS levels significantly increased in tumor cells treated with VC and Q.
NRF2⇅, it was demonstrated that treatment of MDA-MB 231 cells with 25 µM Q increased the expression of Nrf2, while 50 and 75 µM Q decreased the mRNA levels of Nrf2.

2275-

VitK2,

Delivery of the reduced form of vitamin K2(20) to NIH/3T3 cells partially protects against rotenone induced cell death

in-vitro,

Nor,

NIH-3T3

0-3 µM

MK-4, vitamin K2(20)), a safe drug for osteoporosis

*MMP↓, MK-4 and MKH derivatives suppressed cell death, the decline in mitochondrial membrane potential (MMP), excessive reactive oxygen species (ROS) production, and a decrease in intrinsic coenzyme Q9 (CoQ9) induced by rotenone (ROT, complex I inhibitor).
*ROS↓, MK-4 and MKH derivatives suppress ROT-induced ROS
*HO-1↓, MK-4 and MKH derivatives suppress ROT-induced heme oxygenase-1 expression. HO-1 protein expression was clearly increased by ROT

Showing Research Papers: 1 to 45 of 45

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 45

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 2,
Total Targets: 360

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 3, Ferroptosis↓, 1, GPx↑, 3, GSH↑, 3, GSTs↑, 2, HDL↑, 1, HO-1↓, 7, HO-1↑, 2, Iron↓, 1, Keap1↓, 1, Keap1↑, 1, lipid-P↓, 3, MDA↓, 3, NRF2↓, 1, NRF2↑, 5, ROS↓, 8, SIRT3↑, 1, SOD↓, 1, SOD↑, 4, SOD1↑, 2, TAC↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↓, 1, PGC-1α↑, 1,

Core Metabolism/Glycolysis ⓘ

glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 1, PPARγ↑, 1,

Cell Death ⓘ

BAX↓, 1, Casp3↓, 5, Casp9↓, 1, Fas↓, 1, Ferroptosis↓, 1, HGF/c-Met↑, 1, iNOS↓, 2, MAPK↓, 1,

Transcription & Epigenetics ⓘ

other↓, 1,

Protein Folding & ER Stress ⓘ

CHOP↑, 1, ER Stress↓, 1, GRP78/BiP↑, 1, GRP94↑, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1, ERK↓, 1, p‑ERK↑, 1,

Migration ⓘ

AntiAg↑, 1, MMP7↓, 1, Rho↓, 1, TGF-β↓, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IL10↓, 1, IL10↑, 1, IL1β↓, 3, IL6↓, 1, IL8↓, 1, Inflam↓, 4, IκB↑, 1, NF-kB↓, 4, TLR4↓, 2, TNF-α↓, 3,

Protein Aggregation ⓘ

AGEs↓, 1, Aβ↓, 2,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

AST↓, 1, IL6↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, chemoP↑, 1, cognitive↓, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 2, Pain↓, 1, RenoP↑, 1, toxicity↓, 2, Weight∅, 1, Wound Healing↑, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1, Diar↓, 1,
Total Targets: 84

Scientific Paper Hit Count for: HO-1, HMOX1

6 Luteolin
5 diet FMD Fasting Mimicking Diet
4 Chemotherapy
3 Chrysin
3 Vitamin C (Ascorbic Acid)
2 doxorubicin
2 Artemisinin
2 Berbamine
2 Berberine
2 Chlorogenic acid
2 Ellagic acid
1 Allicin (mainly Garlic)
1 Alpha-Lipoic-Acid
1 Cisplatin
1 Baicalein
1 Radiotherapy/Radiation
1 Betulinic acid
1 Brucea javanica
1 brusatol
1 Bromelain
1 Curcumin
1 diet Short Term Fasting
1 Dipyridamole
1 Disulfiram
1 Copper and Cu NanoParticles
1 EGCG (Epigallocatechin Gallate)
1 Hydrogen Gas
1 HydroxyCitric Acid
1 Honokiol
1 Metformin
1 Propyl gallate
1 Resveratrol
1 salinomycin
1 Selenium
1 Oxygen, Hyperbaric
1 Thymoquinone
1 Quercetin
1 Vitamin K2

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#:%  Target#:597  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HO-1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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