Beclin-1 Cancer Research Results

Beclin-1, Beclin-1 (BECN1 gene): Click to Expand ⟱

Source:

Type: Protein Coding gene

Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown.
A key biomarker of autophagy is Beclin-1. Beclin-1 stimulates LC3-I’s lipidation to produce LC3-II, which localizes to the autophagosome membrane to activate the development of autophagosomes.
-BECN1 = the official gene symbol (human gene name)
-Beclin-1 = the protein name encoded by the BECN1 gene

Scientific Papers found: Click to Expand⟱

5263-

3BP,

CET,

3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis

in-vitro,

CRC,

DLD1

NA,

HCT116

eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT/SLC7A11↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

5431-

AG,

Advances in research on the anti-tumor mechanism of Astragalus polysaccharides

Review,

Var,

AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT/SLC7A11↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp/ABCB1↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1/SREBF1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

400-

AgNPs,

MF,

Polyvinyl Alcohol Capped Silver Nanostructures for Fortified Apoptotic Potential Against Human Laryngeal Carcinoma Cells Hep-2 Using Extremely-Low Frequency Electromagnetic Field

in-vitro,

Laryn,

HEp2

50mT/30mins

3.29 0.4 mol/mL

6x improvement when LEMF added (50mT/15mins)

TumCP↓, especially in the G0/G1 and S phases.
Casp3↑,
P53↑,
Beclin-1↑,
TumAuto↑,
GSR↑, oxidative stress biomarker
ROS↑, oxidative stress biomarker
MDA↑, oxidative stress biomarker
ROS↑,
SIRT1↑,
Ca+2↑, induce apoptosis in osteoclasts by increasing intracellular and nucleus Ca2+ concentration
Endon↑, increases endonuclease activity
DNAdam↑,
Apoptosis↑,
NF-kB↓,

387-

AgNPs,

Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells

in-vitro,

Colon,

HT-29

33.45 μg/mL

Cyt‑c↑,
P53↑,
BAX↑,
Casp3↑,
Casp9↑,
Casp12↑,
Beclin-1↑,
CHOP/DDIT3↑,
LC3s↑, LC3-II
XBP-1↑,

250-

AL,

Allicin Induces p53-Mediated Autophagy in Hep G2 Human Liver Cancer Cells

in-vitro,

Liver,

HepG2

 35uM

P53↓, allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway
PI3K↓, decreased the levels of PI3K/mTOR, p-Bcl-2, Bcl-xL, and cytoplasmic p53 in Hep G2 cells.
mTOR↓,
Bcl-2↓,
AMPK↑,
TSC2↑,
Beclin-1↑, llicin increased the levels of Beclin-1, Bad, p-AMPK, TSC2, and Atg7
TumAuto↑, Allicin induced autophagy and increased the formation of autophagosomes and autophagolysosomes in Hep G2 cells.
tumCV↓, Allicin treatment at 35 uM decreased the viability of Hep G2 cells after 12 and 24 h significantly.
ATG7↑,
MMP↓, allicin treatment caused a decrease of MMP of Hep G2 cells and degradation of mitochondria

7396-

Amla,

Enhancing cognitive memory function using Phyllanthus emblica polysaccharides via modulating autophagy and reshaping the gut microbiota

in-vivo,

AD,

mice/rats

*Inflam↓, Phyllanthus emblica polysaccharides (PEP) exhibit anti-inflammatory, antioxidant, and gut microbiota-modulating properties in colitis and obese mice.
*antiOx↓,
*GutMicro↑,
*cognitive↑, In vivo results showed that PEP administration significantly alleviated cognitive decline by reducing neuroinflammatory cytokines (TNF-α, IL-6, and IL-1β) and MDA levels while increasing anti-inflammatory factors (IL-4 and IL-10) and antioxidants (S
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓,
*IL4↑,
*IL10↑,
*TAC↑,
*ATG5↑, Mechanistically, PEP upregulated autophagy-related proteins (Atg5, Beclin1, and LC3B) and LRP1 expression while downregulating AD-related proteins (BACE1, APP, Aβ, and phospho-TauSer404)
*Beclin-1↑,
*LC3B↑,
*LRP1↑,
*BACE/β-secretase↓,
*APP↓,
*Aβ↓,
*tau↓,

7393-

Amla,

Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors

vitro+vivo,

Ovarian,

OVCAR-3

mouse xenograft tumors.

in-vitro,

Ovarian,

SW626

TumCP↓, Amla extract (AE) has anti-proliferative effects on OC cells under both in vitro and in vivo conditions.
Beclin-1↑, AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions.
LC3B-II↑,
Hif1a↓, AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1α (HIF-1α) in OVCAR3 cells.
Dose↝, cell proliferation was significantly inhibited at AE concentrations ranging from 300–1000 µg/ml
TumAuto↑, AE induces autophagy in OVCAR3 and SW626 cells
angioG↓, AE inhibits angiogenesis-related genes in OVCAR3 cells
COL4A3↓, The expression of COL4A3, CXCL6, ECGF1, EFNB2, FGF2, IL1β, PDGFB, TNFRSF12A and HIF-1α were reduced to less than 40% of control levels (Figure 5D), with Hif-1α being inhibited to the greatest extent.
CXCL6/GCP-2↓,
TYMP/ECGF1↓,
IL1β↓,
PDGFRB↓,
ChemoSen↑, AE with cisplatin synergistically reduced cell proliferation in OVCAR3 cells
Dose↝, mice were fed orally with 10% sucrose (control) or 10% sucrose with AE (100 mg/kg body wt.) daily.

584-

Api,

Cisplatin,

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms

in-vivo,

Var,

Eighty Swiss albino male mice

Beclin-1↑, 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities
Casp3↑,
Casp9↑,
JNK↑,
Mcl-1↓, significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity
Ki-67↓, alleviated the histopathological changes with significant decrease of Ki-67 proliferation index

313-

Api,

Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells

in-vitro,

Thyroid,

BCPAP

 25 uM

LC3s↝, conversion of LC3 protein
p62↓,
ROS↑,
TumCCA↑, G2/M cell cycle arrest.
CDC25↓,
TumAuto↑,
Beclin-1↑,
AVOs↑,
DNAdam↑,

3383-

ART/DHA,

Dihydroartemisinin: A Potential Natural Anticancer Drug

Review,

Var,

TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2/KDR/Flk1↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2/PTGS2↓,
MMP9↓,

1528-

Ba,

Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma

in-vitro,

OS,

CAL27

1-100uM

Apoptosis↑,
ROS↑, baicalein triggered reactive oxygen species (ROS) generation in Cal27 cells
eff↓, Furthermore, N-acetyl-cysteine, a ROS scavenger, abrogated the effects of baicalein on ROS-dependent autophagy.
TumAuto↑, baicalein increased autophagy through the promotion of ROS signaling pathways in OSCC.
cl‑PARP↑,
Bax:Bcl2↑,
Beclin-1↑, enhancement of Beclin-1 and degradation of p62
p62↓,

5547-

BBM,

Berbamine exerts anticancer effects on human colon cancer cells via induction of autophagy and apoptosis, inhibition of cell migration and MEK/ERK signalling pathway

in-vitro,

CRC,

HT29

tumCV↓, Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells.
selectivity↑,
Casp3↑, Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio.
Casp9↑,
Bax:Bcl2↑,
ATG5↑, increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1.
Beclin-1↑,
TumCP↓, Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells.
MEK↓,
ERK↓,

2677-

BBR,

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring

in-vivo,

Diabetic,

Rats

*hepatoP↑, berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM)
*LC3II↑, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats.
*Beclin-1↑,
*AMPK↑,
*mTOR↑,
*ER Stress↓, It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation.
*CHOP/DDIT3↓,
*JNK↓,
*ROS↓,
*Inflam↓,
*BG↓, Oral supplementation of diabetic rats either by Lip-BBR or Vild, 10 mg/kg of each, significantly (p < 0.001) lowered the blood glucose levels of tested diabetic rats compared to the diabetic group.
*SOD↑, when the diabetic rats received Lip-BBR, the decrements were less pronounced compared to the diabetic group by 1.16 fold, 2.52 fold, and 67.57% for SOD, GPX, and CAT, respectively.
*GPx↑,
*Catalase↑,
*IL10↑, Treatment of the diabetic rats with Lip-BBR significantly (p < 0.001) elevated serum IL-10 levels by 37.01% compared with diabetic rats.
*IL6↓, Oral supplementation of Lip-BBR could markedly (p < 0.0001) reduce the elevated serum levels of IL-6 and TNF-α when it is used as a single treatment by 55.83% and 49.54%,
*TNF-α↓,
*ALAT↓, ALT, AST, and ALP in the diabetic group were significantly higher (p < 0.0001) by 88.95%, 81.64%, and 1.8 fold, respectively, compared with those in the control group, but this was reversed by the treatment with Lip-BBR
*AST↓,
*ALP↓,

3679-

BBR,

Berberine alleviates Alzheimer's disease by activating autophagy and inhibiting ferroptosis through the JNK-p38MAPK signaling pathway

in-vivo,

AD,

5xFAD mice

*Beclin-1↑, autophagy-related markers Beclin1 and LC3B were upregulated and P62 was downregulated after BBR treatment.
*LC3B↑,
*p62↓,
*ROS↓, ROS and lipid peroxide MDA decreased significantly after BBR treatment.
*lipid-P↓,
*MDA↓,
*Ferroptosis↓, expression levels of ferroptosis-related genes TFR1, ASCL4, DMT1, and IREB2 were decreased, while the expression levels of FTH1 and SLC7A11 increased after BBR treatment.
*TfR1/CD71↓,
*FTH1↑,
*memory↑, BBR treatment enhanced spatial memory impairment in 5xFAD mice.
*JNK↓, inhibited ferroptosis by inhibiting the JNK-P38MAPK signaling pathway.
*p38↓,
*Aβ↓, further reducing Aβ plaque deposition, inhibiting inflammatory response,
*Inflam↓,

4298-

BBR,

Berberine mitigates cognitive decline in an Alzheimer’s Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance

in-vivo,

AD,

in drinking water at 100 mg/kg/day, and lasted four months

3×Tg AD mice

*cognitive↑, Berberine could improve 3×Tg AD mice’s cognitive function
*p‑tau↓, Berberine could attenuate the hyperphosphorylation of tau
*GSK‐3β↓, attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A
*PP2A↑, inhibition of GSK3β or activation of PP2A attenuates tau hyperphosphorylation, thus, ameliorates cognitive impairment
*memory↑, Berberine-treated mice showed better performance in spatial learning and memory test
*Akt↑, Berberine decreases tau phosphorylation via activation of Akt and inhibition of GSK3β
*LC3II↑, both LC3-Ⅱ and Beclin-1 in the hippocampus of BBR-treated group were dramatically increased compared with the 3×Tg AD mice
*Beclin-1↑,

6510-

BCP,

CBD,

Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis

in-vivo,

Nor,

BC (30 mg/kg), CBD (15 mg/kg)

Rats

*MMP↓, BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides.
*ROS↑,
*BloodF↑, while improving blood flow
*Pain↓, CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats.
*antiOx↑,
*Inflam↓,
*AMPK↑, in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions
*SIRT3↑,
*NRF2↑,
*PINK1↑,
*PARK2↑,
*LC3B↑,
*Beclin-1↑,
*TFAM↑,
*NLRP3↓, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted
*NF-kB↓,
*COX2/PTGS2↓,
*p62↓,
*NP/CIPN↓, CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system.

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/PTGS2↓, 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

5678-

BML,

Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy

in-vivo,

CRC,

investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model.

AntiCan↑, Bromelain, an extract of pineapple, was shown to have anticancer effects
TumCG↓, bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models.
ROS↑, induced high levels of ROS and superoxide, plus autophagosome and lysosome formation.
Apoptosis↑, High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9
Endoglin↑,
Casp3↑,
Casp8↑,
Casp9↑,
ATG5↑, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment.
Beclin-1↑,
p62↑,
PARP↑, Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure.

5662-

BNL,

Rad,

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma

vitro+vivo,

GBM,

RadioS↑, We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo.
Beclin-1↑, coincided with increased expression of beclin-1 and LC3.
Hif1a↓, And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E.
mTORC1↓,
EIF4E↓,
TumAuto↑, Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.

739-

Bor,

Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells

in-vitro,

GBM,

U87MG

in-vitro,

Nor,

HMC3

this report calls HMC3 "normal cells"

TumCG↓,
TumCP↓,
TumCCA↑, remarkably reduced S phase in the U87-MG cells (opposite on normal cells)
PCBP1↓,
GSH↓,
GPx4↓,
Beclin-1↑,
MDA↑,
ACSL4↑,
Casp3↑,
Casp7↑,
Ferroptosis↑,
*toxicity↓, exhibited selectivity by having an opposite effect on normal cells (HMC3).

1580-

Citrate,

Citrate activates autophagic death of prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway

in-vitro,

Pca,

PC3

 (0-3 mM)

in-vivo,

PC,

50 mg/kg/day, i.p.)

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

WPMY-1

 (0-3 mM)

Apoptosis↑,
Ca+2↓, Ca2+-chelating property of citrate
Akt↓, downregulation CaMKII/AKT/mTOR pathway
mTOR↓,
selectivity↑, citrate (0-3 mM) did not affect the cell growth of normal prostate epithelial cells (WPMY-1).
TumCP↓, also verified that citrate significantly inhibited the proliferation of PCa cells (PC3 and LNCaP).
cl‑Casp3↑,
cl‑PARP↑, increased the levels of Cleaved caspase3 and Cleaved PARP in prostate cancer cells
LC3‑Ⅱ/LC3‑Ⅰ↑, ratio of LC3-II/I was markedly increased and the expression of p62 was significantly decreased after the treatment of citrate in PCa cells (PC3 and LNCaP).
p62↓,
ATG5↑, citrate also promoted the protein expression of Atg5, Atg7 and Beclin-1 in PCa cells (PC3 and LNCaP).
ATG7↑,
Beclin-1↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII ↓, citrate suppresses the activation of the CaMKI

4772-

CoQ10,

The anti-tumor activities of coenzyme Q0 through ROS-mediated autophagic cell death in human triple-negative breast cells

in-vitro,

BC,

MDA-MB-468

 IC50 values of 4.8, 7.6, and 20.6 µM

in-vitro,

BC,

MDA-MB-231

TumCP↓, Coenzyme Q0 (CoQ0) inhibits proliferation and colony formation in MDA-MB-468 and 231 cells.
Apoptosis↑, CoQ0 induced apoptosis associated with caspase-3 activation and PARP cleavage
Casp3↑,
cl‑PARP↑,
LC3II↑, CoQ0 induced autophagic cell death is accompanied by LC3-II accumulation and AVO formation
eff↓, Antioxidant NAC prevents CoQ0-induced apoptosis and autophagy.
TumCG↓, CoQ0 (Fig. 1A) suppressed TNBC and Hs578T cell growth, as well as dose-dependently reduced cell growth.
Bax:Bcl2↑, CoQ0 increases Bax/Bcl-2 and Beclin-1/Bcl-2 ratio in both TNBC cell lines
Beclin-1↑,
TumAuto↑, CoQ0 induces autophagy, which ultimately results in cell death TNBC cells
ROS↑, CoQ0 activates intracellular ROS generation in TNBC cells. TNBC cells treated with CoQ0 (5 or 7.5 µM for 0–120 min) showed substantially elevated ROS accumulation

4776-

CoQ10,

Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy

vitro+vivo,

Ovarian,

SKOV3

(SKOV-3) cells and xenografted nude mice

ROS↑, CoQ0 triggered intracellular ROS production, whereas antioxidant N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy
eff↓, whereas antioxidant NAC N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy
AntiCan↑, Furthermore, CoQ0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden
Apoptosis↑, Our findings emphasize that CoQ0 triggered ROS-mediated apoptosis and cytoprotective autophagy.
tumCV↓, CoQ0 inhibits viability and growth of human ovarian carcinoma cells
TumCG↓, CoQ0 suppresses tumor growth in SKOV-3 xenografted nude mice
TumCCA↑, CoQ0 induces G2/M cell-cycle arrest and reduces cell-cycle proteins in SKOV-3 cells
LC3s↑, CoQ0 promotes LC3 accumulation and AVOs formation in SKOV-3 cells
ERStress↑, CoQ0 triggers apoptotic death of SKOV-3 cells via mitochondrial and ER-stress signals
Beclin-1↑, CoQ0 increases Beclin-1/Bcl-2 and Bax/Bcl-2, and inhibits HER-2/neu/AKT/mTOR signalling in SKOV-3 cells
Bax:Bcl2↑,
HER2/EBBR2↓,
Akt↓,
mTOR↓,

1571-

Cu,

Copper in cancer: From pathogenesis to therapy

Review,

NA,

*toxicity↝, The toxicity of Cu overload is known to be due, in part, to the release of ROS via the Fenton or Haber-Weiss reaction, causing lipid, protein, DNA, and RNA damage
ROS↑, Cu-induced ROS can induce lipid peroxidation, which raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic.
lipid-P↓,
HNE↑, raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic
MAPK↑, Cu exposure causes an elevation in intracellular ROS levels, which then stimulates the MAPK signaling pathway, increasing JNK/SAPK and p38 homologous activity and phosphorylation levels
JNK↑, Cu-induced ROS continuously activate JNK, promote the production of the AP-1 transcription factor, increase Beclin 1 and Atg7 production, and cause autophagy and apoptosis in tumor cells
AP-1↑,
Beclin-1↑,
ATG7↑,
TumAuto↑,
Apoptosis↑,
HO-1↑, Fang and colleagues consistently found that Cu activates the ROS/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase-1 (NQO1) signaling cascade to induce autophagy
NQO1↑,
mt-ROS↑, Cu NPs induce complete autophagy by enhancing mitochondrial ROS production and inducing autophagy
Fenton↑, generating large amounts of ROS and oxygen via a Fenton-like reaction

471-

CUR,

Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells

in-vitro,

Ovarian,

SKOV3

5, 10, 20, 40 and 80 μM, 24, 48 and 72 h

in-vitro,

Ovarian,

A2780S

Apoptosis↑,
TumAuto↑,
p62↓,
p‑Akt↓,
p‑mTOR↓,
p‑P70S6K↓,
Casp9↑,
PARP↑,
ATG3↑,
Beclin-1↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,

463-

CUR,

Curcumin induces autophagic cell death in human thyroid cancer cells

in-vitro,

Thyroid,

10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h

in-vitro,

Thyroid,

FTC-133

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

8505C

TumAuto↑,
LC3II↑,
Beclin-1↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↑, p-ERK1/2
p62↓,
p‑PDK1↓,
p‑Akt↓,
p‑p70S6↓,
p‑PIK3R1↓,
p‑S6↓,
p‑4E-BP1↓,

404-

CUR,

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy

vitro+vivo,

Lung,

A549

mice

vitro+vivo,

Lung,

H1299

TumAuto↑,
TumCG↓,
TumCP↓,
Iron↑, iron overload
GSH↓, GSH depletion
lipid-P↑, accumulation of intracellular iron and lipid‐reactive oxygen species (ROS), lipid peroxidation
GPx↓, GPX4
mtDam↑, mitochondrial membrane rupture
autolysosome↑,
Beclin-1↑,
LC3s↑,
p62↓,
Ferroptosis↑, via activating autophagy

435-

CUR,

Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway

in-vitro,

Lung,

A549

5, 10, 20 and 40 μM, 24, 48, 72 and 96 h

Apoptosis↑,
TumAuto↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
Beclin-1↑,
p62↓,
PI3K↓,
Akt↓,
mTOR↓,
p‑Akt↓,
p‑mTOR↓,

457-

CUR,

Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling

in-vitro,

GC,

SGC-7901

10, 20 and 40 μM, 24 h

in-vitro,

GC,

BGC-823

TumCP↓,
Apoptosis↑,
TumAuto↑,
P53↑,
PI3K↓,
P21↑,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
Bcl-xL↓,
LC3I↓, LC3I
BAX↑,
Beclin-1↑,
cl‑Casp3↑,
cl‑PARP↑,
LC3II↑,
ATG3↑,
ATG5↑,

448-

CUR,

Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation

in-vitro,

CRC,

HT-29

15, 20 and 25 μM, 48 h

Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

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.

6328-

DRE,

Hydroalcoholic extract of Taraxacum officinale induces apoptosis and autophagy in 4T1 breast cancer cells

in-vitro,

BC,

4T1

330.21, 262.38 and 145.90 µg mL-1 for 24, 48 and 72 hr, respectively.

TumCG↓, HADE inhibited cell growth and proliferation in a dose- and time-dependent manner.
TumCP↓,
Apoptosis↑, The HADE induced 4T1 breast cancer cell death via apoptosis and autophagy.
TumAuto↑,
DNAdam↑, DNA fragmentation was improved as the concentration of HADE increased.
BAX↑, The Bax, Bax/Bcl-2 ratio, p53, Beclin-1 and Atg-7 over-expression as well as Bcl-2 down-regulation were also evident in treated cancer cells.
Bax:Bcl2↑,
P53↑,
Beclin-1↑,
ATG7↑,
Bcl-2↓,
NO↓, The NO production in 4T1 cells was significantly (p < 0.05) decreased in all three concentrations of HADE after 24 hr incubation in a dose-dependent manner (

3205-

EGCG,

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas

Review,

Var,

Review,

AD,

Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP/DDIT3↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

1656-

FA,

Ferulic Acid: A Natural Phenol That Inhibits Neoplastic Events through Modulation of Oncogenic Signaling

Review,

Var,

tyrosinase↓,
CK2↓,
TumCP↓,
TumCMig↓,
FGF↓,
FGFR1↓,
PI3K↓,
Akt↓,
VEGF↓,
FGFR1↓,
FGFR2↓,
PDGF↓,
ALAT↓,
AST↓,
TumCCA↑, G0/G1 phase arrest
CDK2↓,
CDK4↓,
CDK6↓,
BAX↓,
Bcl-2↓,
MMP2↓,
MMP9↓,
P53↑,
PARP↑,
PUMA↑,
NOXA↑,
Casp3↑,
Casp9↑,
TIMP1↑,
lipid-P↑,
mtDam↑,
EMT↓,
Vim↓,
E-cadherin↓,
p‑STAT3↓,
COX2/PTGS2↓,
CDC25↓,
RadioS↑,
ROS↑,
DNAdam↑,
γH2AX↑,
PTEN↑,
LC3II↓,
Beclin-1↓,
SOD↓,
Catalase↓,
GPx↓,
Fas↑,
*BioAv↓, ferulic acid stability and limited solubility in aqueous media continue to be key obstacles to its bioavailability, preclinical efficacy, and clinical use.
cMyc↓,
Beclin-1↑, ferulic acid by elevating the levels of the apoptosis and autophagy biomarkers, including beclin-1, Light chain (LC3-I/LC3-II), PTEN-induced putative kinase 1 (PINK-1), and Parkin
LC3‑Ⅱ/LC3‑Ⅰ↓,

2827-

FIS,

The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment

Review,

Var,

*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2/KDR/Flk1↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2/BIRC3↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

6981-

Form,

Formononetin: a review of its source, pharmacology, drug combination, toxicity, derivatives, and drug delivery systems

Review,

Var,

Review,

AD,

Review,

PSA,

BioAv↝, FMN has only one phenolic hydroxyl group, so it is poorly soluble in water and easily soluble in organic solvents such as methanol, ethyl acetate, and ether.
*memory↑, It had been found that FMN, isolated from Sophora secundiflora, could improve memory problems by restoring the level of oxidative stress in brain tissues and modulating acetylcholinesterase activity. I
*ROS↓, findings suggest that FMN can inhibit oxidative stress in the liver and restore mitochondrial function
*AChE↓,
*NF-kB↓, FMN, the expression levels of the above three decreased and NF-κB activation was inhibited, which may be related to the release of FMN blocking kelch-like ECH-associated protein-1 (Keap1) and activating the nuclear factor erythroid 2-related factor 2
*Keap1↝,
*NRF2↑,
*Inflam↓, FMN exerted anti-neuroinflammatory effects by targeting peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and bidirectionally regulating NF-κB signaling pathway and Nrf2/Heme oxygenase-1 (HO-1) signaling pathway,
*PGC-1α↝,
*HO-1↓,
*p‑tau↓, thereby inhibiting tau protein hyperphosphorylation.
*cognitive↑, Significantly FMN improve cognitive dysfunction in mice caused by high-fat feeding
*BDNF↑, increased BDNF and 5-hydroxytryptamine (5-HT) levels, and mitigated the progression of depression in mice.
*5HT↑,
*Stroke↓, It could significantly reduce the level of inflammatory factors, increase the number of dendritic spines in neurons, and increase the expression of βIII-tubulin, growth-associated protein 43 (GAP-43), nerve growth factor (NGF) and BDNF.
*PARP1↓, FMN significantly reduced PARP1, PARG, apoptosis-inducing factor (AIF), cysteinyl aspartate-specific protease 3 (caspase-3) and p53 protein in rats with cerebral ischemia-reperfusion injury
*AIF↓,
*Casp3↓,
NP/CIPN↓, FMN had a favorable ameliorative effect on oxaliplatin-induced peripheral neuropathy and did not affect the chemotherapeutic function of oxaliplatin.
*neuroP↑, The neuroprotective mechanism of FMN is shown in Figure 2.
*NGF↑,
*TNF-α↓,
*IL1β↓,
*IL18↓,
*IL6↓,
*VCAM-1↓,
*pol-M2 MC↑,
*hepatoP↑, could reduce hepatotoxicity and improve liver function through inflammatory molecular pathways.
*AST↓, reduce serum AST, ALT, TNF-α and IL-1β levels. I
*ALAT↓,
*LC3II↑, the levels of LC3II, Beclin1, p62, cyclooxygenase-2 (COX2), COX4, MMP and adenosine triphosphate (ATP) were increased
*Beclin-1↑,
*p62↑,
*COX2/PTGS2↑,
*MMP↑,
*ATP↑,
*GSH↑, activity of antioxidant proteins glutathione (GSH), catalase (CAT), GSH-PX in the FMN treatment group recovered, and the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) decreased.
*Catalase↑,
*GPx↑,
*MDA↓,
*antiPs↑, it was found that the interferon (IFN) signaling pathway was inhibited, which could effectively reduce the expression of related inflammatory chemokines, and significantly improve the erythema, scales and thickness of skin lesions in the psoriasis m
*AntiDiabetic↑, FMN effectively mitigated alloxan-induced pancreatic β-cell and DNA damage, lowered blood glucose levels, and increased insulin content.
*glucose↓,
*Insulin↑,
*GutMicro↑, FMN could act as a prebiotic to regulate intestinal microbial flora, thereby improving host metabolism and preventing obesity
*Obesity↓,
COX2/PTGS2↓, FMN effectively inhibited the proliferation of KYSE170 and KYSE150 cells by significantly reducing the mRNA and protein expression levels of COX-2 and cyclin D1, while inducing G1 phase arrest.
cycD1/CCND1↓,
TumCCA↑,
EGFR↓, FMN binds to both WT and mutant EGFR, reducing EGFR kinase activity and inhibiting downstream signaling.
GSK‐3β↑, This, in turn, activated GSK-3β and decreased the expression of myeloid leukemia sequence 1 (Mcl-1), without causing significant toxicity to the vital organs of mice.
Mcl-1↓,
*toxicity↓,
TumCP↓, FMN inhibited the proliferation and growth of cervical cancer cells by inhibiting the expression of HIF-1-α and VEGF.
Hif1a↓,
VEGF↓,
ERK↓, can achieve antiproliferative and invasive effects through effective inhibition of the oncogenic ERK1/2 pathway and the Lamin A/C signaling pathway,
LAMs↓,
Cyt‑c↑, FMN, as a candidate anticancer drug, could release cytochrome C (cyto C) directly through the mitochondrial pathway and activate the cascade reaction of caspase-9, caspase-3 and PARP, which ultimately lead to FaDu cell death
Casp9↑,
Casp3↑,
PARP↑,
TumCD↑,
mitA↑, FMN inhibited mitosis by inactivating the BACH1/p53 signaling pathway, promoted the release of cyto C
BACH1↓,
P53↓,
ROS↑, FMN delivered ROS to mitochondria to release cyto C and activated caspase-3 and caspase-9 cascade reactions to induce apoptosis in MCF7 cells
PD-1↓, FMN has the potential to serve as a PD-1/PD-L1 inhibitor for clinical use
NF-kB↓, FMN mainly interfered with PD-L1 activation by inhibiting the STING-NF-κB signaling pathway
*Bacteria↓, possess other pharmacological activities, such as antibacterial, antiviral, and antiallergic
*AntiViral↑,
*mt-ROS?, FMN effectively reduced the accumulation of ROS and mitochondrial damage in hair cells by activating the PI3K/AKT-Nrf2 signaling pathway, restored the balance of GSH/GSSG.
*PI3K↓,
*chemoP↑, FMN was a potential therapeutic agent for cisplatin-induced ototoxicity.
ChemoSen↑, Therefore, combination therapy had better control effects on multiple targets and a lower risk of drug resistance, which had great application prospects for treating cancer.
eff↑, combination of FMN (30 μM) and sulforaphane (20 μM) exhibited a significant synergistic effect
*toxicity↓, Therefore, it was proved that FMN was safe and non-toxic and could be used for pharmacological and therapeutic purposes.
*BioAv↑, water solubility problem of FMN, succinylated FMN using Bacillus amyloliquefaciens FJ18 to form the compound FMN-7-O-β-D (6″-O-succinyl)-D-glucoside (FMP), which compared to FMN, the water solubility was increased more than 106-fold.
*BioAv↑, To solve those problems, structural modification and nano-delivery systems can be used as a promising solution
*eff↑, FMN can be combined with other treatments, such as immunotherapy, to enhance the therapeutic effect and improve the prognosis of patients;

6984-

Form,

Formononetin suppresses colitis-associated colon cancer by targeting lipid synthesis and mTORC2/Akt signaling

in-vitro,

Colon,

HCT116

Review,

IBD,

RAW264.7

*Inflam↓, Modern research highlights Formononetin (FN) for its significant anti-inflammatory and extensively studied anti-cancer properties;
AntiCan↑,
*NF-kB↓, FN can inhibit the activation of the NF-κB/MAPK signaling pathways in LPS-induced RAW264.7 cells, thereby exerting its anti-inflammatory effects.
*MAPK↓,
*colonLen↑, FN significantly enhanced the colon length and DAI score in mice, notably suppressed the production of inflammatory cytokines, and inhibited the NF-κB/MAPK signaling pathway, leading to an improvement in DSS-induced colitis.
TumCG↓, FN significantly inhibited CT-26 and HCT116 cell growth, reduced tumor growth rate, improved pathological damage in CAC mice, and inhibited inflammatory factor production, enhancing intestinal mucosa protection.
Apoptosis↑, FN promoted apoptosis of colon cancer cells by increasing autophagy proteins (LC3, Beclin-1) and apoptosis proteins (CL-Caspase3, Bax), while reducing Bcl-2 expression.
LC3II↑,
Beclin-1↑,
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
IGF-1↓, FN reduced IGF-1, ACLY, A-CoA, FAS, HSL, ATGL, and FFA levels, and increased GSK-3 levels
ACLY↓,
Acetyl-CoA↓,
Fas↓,
HSL/LIPE↓,
ATGL/PNPLA2↓,
FFA/NEFA↓,
GSK‐3β↑,
p‑mTOR↓, FN also inhibited the expression of P-mTOR, Rictor, P-Akt, ACLY, PDE3B, P-PKA, and P-HSL
Rictor↓,
p‑Akt↓,
PDE3B↓,
p‑PKA↓,
p‑HSL/LIPE↑,
TumAuto↑, FN significantly inhibits colon cancer cell growth and exerts anti-CAC effects by activating autophagy and apoptosis pathways and regulating lipid metabolism.

1962-

GamB,

HCQ,

Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species

in-vitro,

PC,

LC3II↑, Gambogic acid induced the expression of LC3-II and Beclin-1 proteins in pancreatic cancer cells, whereas the expression of P62 showed a decline.
Beclin-1↑,
p62↓,
MMP↓, gambogic acid reduced the mitochondrial membrane potential and promoted ROS production, which contributed to the activation of autophagy
ROS↑,
TumAuto⇅, up by GamB, down by HCQ
eff↑, inhibition of autophagy by chloroquine further reduced the mitochondrial membrane potential and increased the accumulation of ROS

1970-

GamB,

Gambogic acid-induced autophagy in nonsmall cell lung cancer NCI-H441 cells through a reactive oxygen species pathway

NA,

Lung,

NCI-H441

TumCG↓, NCI‑H441 is a human lung adenocarcinoma cell line that is widely used as a model system for studying pulmonary epithelial functions, particularly those of alveolar type II cells.
TumAuto↑, GA induced NCI-H441 cells autophagy
Beclin-1↑, upregulation of Beclin 1
LC3‑Ⅱ/LC3‑Ⅰ↑, conversion of LC3 I to LC3 II (autophagosome marker)
ROS↑, generated ROS
eff↓, ROS scavenger N-acetylcysteine reversed GA-induced autophagy and restored the cell survival, which indicated GA-induced autophagy in NCI-H441 cells through an ROS-dependent pathway.

7102-

GEN,

Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits

Review,

Var,

*antiOx↑, reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities
*Inflam↓,
*Bacteria↓,
*AntiViral↑,
*Dose↝, the most genistein-rich foods are those fermented (miso and natto), which contain 38.5-230 μg/g of genistein, due to the β-glycosyl bond cleavage of genistin (7-O-β-D-glucoside form of genistein, naturally occurring in plants) by microbes during the
*AntiDiabetic↑, figure 1
angioG↑, In the low concentration (0.001–1 μM), genistein induced angiogenesis by promoted tube formation.
Apoptosis↑, Neuroblastoma IMR-32 SK-N-BE2 ↑Apoptosis, ↓cell viability, ↑Myd88, ↑Beclin 1, ↑LC3 II, ↑TLR4, ↑autophagy, ↓mTOR, ↓p62
tumCV↓,
MyD88↑,
Beclin-1↑,
LC3II↑,
TLR4↑,
TumAuto↑,
mTOR↓,
p62↓,
TumCCA↑, SK-N-SH ↑Cell cycle arrest at phase G2/M, ↓proliferation, ↑Akt, ↑CHD5, ↑p53, ↓neuroblastoma growth, ↓tumor microvessel formation, ↓DNMT3b, ↑ERE, ↑luciferase, ↑MEK
TumCP↓,
Akt↑,
P53↑,
DNMT3B↓,
MEK↓,
hTERT/TERT↓, ↓hTERT, ↓VEGF, ↓NF-κB, ↓c-IAP2, ↓MDR, ↓N-Myc, ↓FGF2, ↓p-Ak
VEGF↓,
NF-kB↓,
IAP1↓,
MDR1↓,
p‑Akt↓,
eff↑, There is synergistic efficiency of genistein and sorafenib (SF) combined treatment in human malignant neuroblastoma SH-SY5Y (
ChemoSen↑, Genistein has no special effect on P-gp function, but it boosts up the intracellular accumulation of doxorubicin

2507-

H2,

Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis

in-vivo,

NA,

Sprague-Dawley rats

*RenoP↑, We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats.
*ROS↓,
*Apoptosis↓,
*ER Stress↓, endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated
*CHOP/DDIT3↓,
*Casp12↓,
*GRP78/BiP↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑, higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated.
*Beclin-1↑,
*p62↓,
*mTOR↓, Inhibition of mTOR may be involved in the upregulation of autophagy by H2

7365-

HibSad,

Insight into the molecular evidence supporting the remarkable chemotherapeutic potential of Hibiscus sabdariffa L

Review,

Var,

chemoPv↑, Both crude extracts and pure compounds of the plant were reported to induce chemoprevention, selective cytotoxicity, cell cycle arrest, apoptosis, autophagy and anti-metastasis effects in varied types of human cancer cells.
selectivity↑,
TumCCA↑,
Apoptosis↑,
TumAuto↑,
TumMeta↓,
ATG5↑, figure 3
Beclin-1↑,
LC3II↑,
MMP2↓,
MMP9↓,
CD31/PECAM-1↓,
VEGF↓,
uPA↓,
TIMP2↑,
NF-kB↓,
p38↑,
P53↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-2↓,
BAX↑,
Cyt‑c↑,
TNF-α↑,
Fas↑,
FasL↑,
JNK↑,
cJun↑,
angioG↓,
VEGFR2/KDR/Flk1↓,
PCNA↓,
CCN2/CTGF↓,
RAGE↓,

7353-

HibSad,

Hibiscus sabdariffa Leaf Polyphenolic Extract Induces Human Melanoma Cell Death, Apoptosis, and Autophagy

in-vitro,

Melanoma,

A375

cl‑Casp↑, Our results revealed that both HLP and ECG induced the caspases cleavages, Bcl-2 family proteins regulation, and Fas/FasL activation in A375 cells.
Bcl-2↓,
Fas↑,
FasL↑,
ATG5↑, HLP could increase the expressions of autophagy-related proteins autophagy-related gene 5 (ATG5), Beclin1, and light chain 3-II (LC3-II), and induce autophagic cell death in A375 cells.
Beclin-1↑,
LC3B-II↑,
TumAuto↑,

2865-

HNK,

Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma

in-vitro,

MB,

DAOY

vitro+vivo,

NA,

BioAv↓, poor water solubility of HNK results in its low bioavailability, thus limiting its wide use in clinical cancer treatments
BioAv↓, Liposomes can overcome this limitation, and liposomal HNK (Lip-HNK) has promising clinical applications in this aspect
TumCP↓, increased Lip-HNK concentration could inhibit the proliferation of DAOY and D283 cells, without exerting effects on the growth of non-tumor cells
selectivity↑,
P53↑, P53 and P21 proteins (inhibiting cell cycle progression) was increased
P21↑,
CDK4↓, Lip-HNK also downregulated the expression of CDK4 and cyclin D1
cycD1/CCND1↓,
mtDam↑, Lip-HNK caused apoptosis and death, which, in turn, led to the failure of mitochondrial membrane function
ROS↑, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
eff↓, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
Casp3↑, caspase-3 sectioned and the Bax protein level increased by Lip-HNK
BAX↑,
LC3II↑, LC3BII protein in the Lip-HNK-treated group was noticeably elevated
Beclin-1↑, Beclin-1 (BECN), Atg7 proteins, and LC3BII were dramatically upregulated in the Lip-HNK-treated cells
ATG7↑,
p62↑, Lip-HNK treatment remarkably increased p62 expression, which was dose-dependent
eff↑, Lip-HNK treatment (20 mg/kg) drastically inhibited tumor growth. The combined treatment of Lip-HNK, Chloroquine , and Carboplatin showed more superior antitumor effects
ChemoSen↑, Lip-HNK alone or combined with chemotherapy (Carboplatin or Etoposide) causes significant regression of orthotopic xenografts
*toxicity↓, We also found that Lip-HNK did not damage the liver and kidney

7855-

isoO,

Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells

in-vitro,

Liver,

HepG2

in-vitro,

Nor,

HL7702

TumAuto↑, ISO induced autophagy, which was correlated with the formation of autophagic vacuoles and the overexpression of Beclin-1 and LC3-II.
Beclin-1↑,
LC3II↑,
eff↓, Also, the reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine (NAC), the JNK inhibitor SP600125, and the p38 inhibitor SB203580 efficiently downregulated the levels of these proteins.
ROS↑, by ROS-related p53, PI3K/Akt, JNK, and p38 signaling pathways
Fas↑, ISO-induced apoptosis by activating the Fas receptor-mediated apoptotic pathway and suppressing the p53 and PI3K/Akt-dependent NF-κB signaling pathway,
P53↓,
PI3K↓,
Akt↓,
NF-kB↓,
Cyt‑c↑, with the subsequent increase in the release of cytochrome c, caspase-3 activation, and PARP cleavage.
Casp3↑,
cl‑PARP↑,

7794-

ISQ,

Isoquercitrin induces apoptosis and autophagy in hepatocellular carcinoma cells via AMPK/mTOR/p70S6K signaling pathway

in-vitro,

Liver,

HepG2

in-vitro,

Liver,

HUH7

tumCV↓, ISO exposure inhibited cell viability and colony growth, activated apoptotic pathway, and triggered dysregulated autophagy by activating the AMPK/mTOR/p70S6K pathway.
Apoptosis↑,
TumAuto↑, Isoquercitrin induces autophagy in HCC cells
AMPK↑,
TumCG↓, Isoquercitrin inhibits HCC cell growth
ATG5↑, dose-dependent increase in LC3, Atg5, and Beclin-1, and a decrease in p62/sequestosome-1 (p62) expression, in HepG2 and Huh7 cells treated with ISO for 48 h
Beclin-1↑,
p‑mTOR↓, As expected, ISO treatment led to dose-dependent activation of AMPK and decreased the phosphorylation of mTOR and its downstream substrate p70/p85S6 kinase (p70/p85S6K)
Casp3↑, ISO actions were characterized by up-regulation of active caspase-3 and cleaved PARP and increased Bax/Bcl-2 ratio, indicative of apoptosis, concomitant with enhanced LC3-II expression and p62 degradation, reflecting induction of autophagy
cl‑PARP↑,
Bax:Bcl2↑,
LC3II↑,
p62↓,

7893-

IVT,

Isovitexin (IV) induces apoptosis and autophagy in liver cancer cells through endoplasmic reticulum stress

vitro+vivo,

Liver,

TumCG↓, we showed that IV significantly suppressed the growth of liver cancer cells
Apoptosis↑, IV induced apoptosis by the mitochondrial apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria.
BAX↑,
cl‑Casp3↑,
cl‑PARP↑,
Cyt‑c↑,
TumAuto↑, IV resulted in autophagy in liver cancer cells, supported by the enhancement of LC3II, autophagy-related protein (Atg) 3, Atg5 and Beclin1.
LC3II↑,
ATG3↑,
ATG5↑,
Beclin-1↑,
ER Stress↑, IV was found to cause endoplasmic reticulum (ER) stress in liver cancer cells, along with the promotion of ER stress-related molecules, including inositol-requiring enzyme 1α (IRE1α), X-box-binding protein-1s (XBP-1s), C/EBP homologous protein (CHO
IRE1↑,
XBP-1↑,
CHOP/DDIT3↑,
GRP78/BiP↑, and glucose-regulated protein (GRP)-78
*chemoPv↑, IV could therefore be a strong candidate for liver cancer prevention.

5118-

JG,

Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells

in-vitro,

HCC,

HepG2

m-ROS↑, JG-induced ROS production caused oxidative damage to mitochondria and DNA
DNAdam↑,
Apoptosis↑, JG kills HepG2 cells through the induction of apoptosis.
TumAuto↑, JG triggers autophagy, which contributes to JG-induced cell death.
p38↑, The autophagic cell death was dependent on ROS generation and the activation of p38 MAPK and JNK pathways.
MAPK↑,
JNK↑,
MMP↓, closely related with loss of mitochondrial membrane potential,
LC3II↑, increased expressions of LC3-II and Beclin-1
Beclin-1↑,

1917-

JG,

Inhibition of human leukemia cells growth by juglone is mediated via autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion

in-vitro,

AML,

HL-60

0-80uM

selectivity↑, revealed significant, selective (less cytotoxicity towards normal cells) and dose-dependent inhibition of HL-60 leukemia cells
LC3I↑, significant increase in LC3-I and LC3-II
LC3II↑,
Beclin-1↑, slight increase in Beclin-I
ROS↑, Confocal microscopy revealed tremendous increase in ROS concentrations in a dose-dependent manner
tumCV↓,
Dose↝, ROS percentage was 8%, with 20 μM dose it was 25% and with 80 μM its highest value was observed. dose-dependent increase in ROS production
TumAuto↑, The growth inhibitory effects of juglone were mediated via autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion.

2921-

LT,

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

Review,

Nor,

*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1/SREBF1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP/DDIT3↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

Showing Research Papers: 1 to 50 of 64
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 64

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 1,
Total Targets: 315

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

colonLen↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 5, Catalase↑, 2, Ferroptosis↓, 1, GPx↑, 2, GSH↑, 2, HO-1↓, 1, HO-1↑, 1, Keap1↝, 1, lipid-P↓, 1, MDA↓, 4, MPO↓, 1, NQO1↑, 1, NRF2↑, 3, PARK2↑, 1, ROS↓, 6, ROS↑, 1, mt-ROS?, 1, SIRT3↑, 1, SOD↑, 2, TAC↑, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

FTH1↑, 1, TfR1/CD71↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↓, 1, ATP↑, 1, Insulin↑, 1, MMP↓, 1, MMP↑, 1, PGC-1α↝, 1, PINK1↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 3, AMPK↑, 3, glucose↓, 2, LDL↓, 1, PPARα↑, 1, SIRT1↑, 1, SREBP1/SREBF1↓, 1,

Cell Death(tgid=5) ⓘ

Akt↑, 1, Apoptosis↓, 1, BAX↓, 1, Casp1↓, 1, Casp12↓, 1, Casp3↓, 1, Cyt‑c↓, 1, Ferroptosis↓, 1, iNOS↓, 1, JNK↓, 2, MAPK↓, 1, p38↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

TFAM↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 3, ER Stress↓, 3, GRP78/BiP↓, 1,

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1, Beclin-1↑, 7, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, LC3B↑, 3, LC3II↑, 3, p62↓, 3, p62↑, 1,

DNA Damage & Repair(tgid=10) ⓘ

PARP1↓, 1,

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

GSK‐3β↓, 1, mTOR↓, 1, mTOR↑, 1, PI3K↓, 1,

Migration(tgid=13) ⓘ

APP↓, 1, Ca+2?, 1, LRP1↑, 1, TXNIP↓, 1, VCAM-1↓, 1, ZO-1↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1, COX2/PTGS2↑, 1, IFN-γ↓, 1, IL10↑, 2, IL18↓, 2, IL1β↓, 3, IL2↓, 1, IL4↑, 1, IL6↓, 4, Inflam↓, 11, pol-M2 MC↑, 1, NF-kB↓, 4, TLR4↓, 1, TNF-α↓, 3,

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↑, 1, AChE↓, 1, BDNF↑, 1, NGF↑, 1, tau↓, 1, p‑tau↓, 2,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2, BACE/β-secretase↓, 1, NLRP3↓, 2, PP2A↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 2, Dose↝, 1, eff↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 3, ALP↓, 1, AST↓, 3, BG↓, 1, BloodF↑, 1, GutMicro↑, 3, IL6↓, 4,

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 2, antiPs↑, 1, cardioP↑, 1, chemoP↑, 1, chemoPv↑, 1, cognitive↑, 3, hepatoP↑, 3, memory↑, 4, neuroP↑, 2, NP/CIPN↓, 1, Obesity↓, 1, Pain↓, 2, RenoP↑, 1, toxicity↓, 4, toxicity↝, 1, Wound Healing↑, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 2, Bacteria↓, 3, Diar↓, 1,
Total Targets: 128

Scientific Paper Hit Count for: Beclin-1, Beclin-1 (BECN1 gene)

6 Curcumin
3 Berberine
3 Luteolin
2 Silver-NanoParticles
2 Magnetic Fields
2 Phyllanthus emblica/Emblica officinalis/Amla / Indian Gooseberry
2 Apigenin (mainly Parsley)
2 Bromelain
2 Coenzyme Q10
2 Formononetin
2 Gambogic Acid
2 Hibiscus sabdariffa
2 Juglone
2 Thymoquinone
1 3-bromopyruvate
1 cetuximab
1 Astragalus
1 Allicin (mainly Garlic)
1 Cisplatin
1 Artemisinin
1 Baicalein
1 Berbamine
1 Beta-Caryophyllene
1 Cannabidiol
1 borneol
1 Radiotherapy/Radiation
1 Boron
1 Citric Acid
1 Copper and Cu NanoParticles
1 diet FMD Fasting Mimicking Diet
1 Chemotherapy
1 Dandelion Root
1 EGCG (Epigallocatechin Gallate)
1 Ferulic acid
1 Fisetin
1 hydroxychloroquine
1 Genistein (soy isoflavone)
1 Hydrogen Gas
1 Honokiol
1 isoorientin
1 isoquercitrin
1 Isovitexin
1 Magnetic Field Rotating
1 Phenylbutyrate
1 Parthenolide
1 Quercetin
1 Resveratrol
1 Silymarin (Milk Thistle) silibinin
1 Shikonin
1 Spermidine
1 Selenite (Sodium)
1 Urolithin

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#:30  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

Beclin-1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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