Database Query Results : Fisetin, ,

FIS, Fisetin: Click to Expand ⟱
Features:
Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes.

-Note half-life 3-4hrs
- Oral BioAv low (40-50%)
Pathways:
- induce ROS production in cancer cells, but also known to reduce it.
Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells
Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Does not appear to lower antioxidants in cancer cells
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CD133↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


Scientific Papers found: Click to Expand⟱
2854- FIS,    New Perspectives for Fisetin
- Review, Var, NA - Review, Stroke, NA
"highlight2" >Inflam↓, anti-inflammatory, chemopreventive, chemotherapeutic
"highlight2" >ChemoSen↑,
"highlight2" >chemoP↑,
"highlight2" >eff↑, fisetin significantly impairs carcinoma cell growth in the presence of ascorbic acid, which results in a 61% inhibition of cell growth, in 72 h; the treatment with ascorbic acid alone had no effect on cellular proliferation (Kandaswami et al., 1993)
"highlight2" >memory↑, enhancement of the long-term memory, antidepressant effects, inhibition of ischemic reperfusion injury and amelioration of behavioral deficits following a stroke
"highlight2" >neuroP↑,
"highlight2" >*Dose↑, Mayo Clinic has recently designed and begun a clinical trial aimed at the “Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults” (AFFIRM-LITE) with fisetin orally in doses up to 20 mg/kg of patient body weight
"highlight2" >BioAv↓, In view of poor solubility (10.45 μg/mL), relatively low oral bioavailability (44%) and rapid metabolism,
"highlight2" >BBB↑, fisetin in combination with other epigenetically active molecules which are able to cross the blood-aqueous and blood-retina barriers exhibit synergistic beneficial effects.

2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
"highlight2" >PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >p38↓,
"highlight2" >*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
"highlight2" >*neuroP↑,
"highlight2" >Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
"highlight2" >Bcl-2↓,
"highlight2" >Mcl-1↓,
"highlight2" >BAX↑,
"highlight2" >BIM↑,
"highlight2" >BAD↑,
"highlight2" >AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
"highlight2" >ACC↑,
"highlight2" >DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
"highlight2" >MMP↓,
"highlight2" >eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
"highlight2" >ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
"highlight2" >cl‑PARP↑, fisetin treatment resulted in PARP cleavage
"highlight2" >Cyt‑c↑, release of cyt. c
"highlight2" >Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
"highlight2" >P53↑, increased p53 protein levels
"highlight2" >p65↓, reduced phospho-p65 and Myc oncogene expression
"highlight2" >Myc↓,
"highlight2" >HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
"highlight2" >HSP27↓,
"highlight2" >COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
"highlight2" >Wnt↓,
"highlight2" >EGFR↓,
"highlight2" >NF-kB↓,
"highlight2" >TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
"highlight2" >CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
"highlight2" >CDK4↓,
"highlight2" >cycD1↓,
"highlight2" >cycA1↓,
"highlight2" >P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
"highlight2" >MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
"highlight2" >MMP9↓,
"highlight2" >TumMeta↓, Antimetastasis
"highlight2" >MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
"highlight2" >MMP3↓,
"highlight2" >MMP7↓,
"highlight2" >MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
"highlight2" >N-cadherin↓,
"highlight2" >Vim↓,
"highlight2" >Snail↓,
"highlight2" >Fibronectin↓,
"highlight2" >E-cadherin↑,
"highlight2" >uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
"highlight2" >ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
"highlight2" >EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
"highlight2" >Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
"highlight2" >Zeb1↓,
"highlight2" >cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
"highlight2" >cJun↓,
"highlight2" >EGF↓, Fisetin inhibited epidermal growth factor (EGF)
"highlight2" >angioG↓, Antiangiogenesis
"highlight2" >VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
"highlight2" >eNOS↓,
"highlight2" >*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
"highlight2" >HO-1↑,
"highlight2" >NRF2↓, Fisetin also triggered the suppression of Nrf2
"highlight2" >GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
"highlight2" >ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

2846- FIS,    Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity
- in-vitro, Nor, NA
"highlight2" >*cardioP↑, Fisetin enhances viability of rat cardiomyocytes following hypoxia/starvation – reoxygenation.
"highlight2" >*ROS↓, It inhibits apoptosis, decreases ROS generation and caspase activation and protects from DNA damage
"highlight2" >*Casp↓,
"highlight2" >*DNAdam↓,

2847- FIS,    Fisetin-induced cell death, apoptosis, and antimigratory effects in cholangiocarcinoma cells
- in-vitro, CCA, NA
"highlight2" >tumCV↓, Fisetin was significant in suppressing CCA cell viability and colony formation during the course of this experiment.
"highlight2" >ChemoSen↑, fisetin significantly potentiated the cisplatin-induced CCA cells death
"highlight2" >TumCMig↓, reduced the migration of cancer cells and demonstrated more pronounced effects on KKU-M452 cells
"highlight2" >ROS↑, fisetin prompted cell death and apoptosis in CCA cells by stimulating the generation of ROS in KKU-100 cells at a dosage of 50 μM
"highlight2" >TumCI↓, suppression of cell invasion and migration,prevention of angiogenesis
"highlight2" >angioG↓,
"highlight2" >CDK2↓, mechanisms including the suppression of cyclin-dependent kinases, the inhibition of PI3K/Akt/mTOR
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >EGFR↓, suppression of the EGFR pathway, the stimulation of the caspase cascade
"highlight2" >Casp↑,
"highlight2" >mTORC1↓, suppressing the mTORC1 and 2 signaling
"highlight2" >mTORC2↑,
"highlight2" >cycD1↓, decreasing the level of the cyclin D1 and cyclin E mRNA
"highlight2" >cycE↓,
"highlight2" >MMP2↓, Matrix metalloproteinases (MMP) 2 and MMP 9 gene expression and enzyme activity are suppressed
"highlight2" >MMP9↓,
"highlight2" >ER Stress↑, Moreover, fisetin also caused endoplasmic reticulum (ER) stress-induced production of mitochondrial ROS generation and Ca2+, with the involvement of MAPK signaling
"highlight2" >Ca+2↑,
"highlight2" >eff↓, The ROS scavenger molecule N-acetyl cysteine decreased fisetin-activated apoptosis in multiple myeloma and oral cancer cells

2848- FIS,    Fisetin alleviates cellular senescence through PTEN mediated inhibition of PKCδ-NOX1 pathway in vascular smooth muscle cells
- in-vitro, Nor, NA
"highlight2" >*ROS↓, Therefore, we hypothesized that the anti-aging effect of fisetin might involve regulation of the PKCδ-ROS production signaling pathway via PTEN activation in VSMC.
"highlight2" >*PTEN↑,
"highlight2" >*PKCδ↑, Fisetin-mediated PKCδ activation suppressed the inflammatory signaling pathway in human airway epithelial cells (Lee et al., 2018) and protected human umbilical vein endothelial cells from oxidative stress
"highlight2" >*Inflam↓,

2849- FIS,    Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
- in-vitro, Melanoma, U266
"highlight2" >TumCD↑, Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling
"highlight2" >TumCCA↑,
"highlight2" >Casp3↑, Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1L, and upregulation of Bax, Bim and Bad
"highlight2" >Bcl-2↓,
"highlight2" >Mcl-1↓,
"highlight2" >BAX↑,
"highlight2" >BIM↑,
"highlight2" >BAD↑,
"highlight2" >AMPK↑, Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of AKT and mTOR.
"highlight2" >ACC↑,
"highlight2" >p‑Akt↓,
"highlight2" >p‑mTOR↓,
"highlight2" >ROS↑, Fisetin also stimulated generation of ROS in U266 cells
"highlight2" >eff↓, Conversely, compound C or N-acetyl-l-cystein blocked fisetin-induced apoptosis

2850- FIS,    Fisetin regulates TPA-induced breast Cancer cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways
- in-vitro, BC, MCF-7
"highlight2" >TumCI↓, Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways.
"highlight2" >PKCδ↓,
"highlight2" >ROS↓,
"highlight2" >ERK↑,
"highlight2" >p38↓,
"highlight2" >NF-kB↓, reduced NF-κB activation
"highlight2" >MMP9↓, reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression.

2851- FIS,    Apoptosis induction in breast cancer cell lines by the dietary flavonoid fisetin
- in-vitro, BC, MDA-MB-468 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, BC, T47D - in-vitro, BC, SkBr3 - in-vitro, Nor, NA
"highlight2" >tumCV↓, Fisetin exhibited a dose- and time-dependent cytotoxic effect on breast cancer cell lines (e.g., 100 µM fisetin decreased MDA-MB-468 cell viability by 70% at 72h
"highlight2" >selectivity↑, In contrast, the viability of normal cells was not substantially affected by concentrations of fisetin that killed breast cancer cells.
"highlight2" >TumCCA↑, Fisetin-treated breast cancer cells showed cell cycle arrest (MDA-MB-468 cells arrested at G2/M phase; MDA-MB-231 cells arrested in S-phase) and death by apoptosis
"highlight2" >Apoptosis↑,
"highlight2" >ROS∅, fisetin did not cause ROS production in MDA-MB-468 or 231 cells, indicating that ROS do not contribute to the cytotoxic effect of fisetin

2852- FIS,    A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms
- Review, CRC, NA
"highlight2" >Risk↓, Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC)
"highlight2" >P53↑, increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction
"highlight2" >MDM2↓,
"highlight2" >COX2↓, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways
"highlight2" >Wnt↓,
"highlight2" >NF-kB↓,
"highlight2" >CDK2↓, regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels
"highlight2" >CDK4↓,
"highlight2" >p‑RB1↓,
"highlight2" >cycE↓,
"highlight2" >P21↑,
"highlight2" >NRF2↓, Pandey and Trigun revealed that fisetin induces apoptosis in CRC cells by inhibiting autophagy and suppressing Nrf2
"highlight2" >ROS↑, Furthermore, fisetin elevated ROS levels and downregulated Nrf2 expression, indicating Nrf2 suppression in fisetin-induced apoptosis in CRC cells.
"highlight2" >Casp8↑, fisetin treatment resulted in the upregulation of various molecular pathways, including cleaved caspase-8, Fas ligand, TRAIL, and DR5 levels, in the cancer cells
"highlight2" >Fas↑,
"highlight2" >TRAIL↑,
"highlight2" >DR5↑,
"highlight2" >MMP↓, Fisetin also caused mitochondrial membrane depolarization, leading to the release of Smac/DIABLO and cytochrome c
"highlight2" >Cyt‑c↑,
"highlight2" >selectivity↑, enhanced cellular uptake, and induction of apoptosis in cancer cells
"highlight2" >P450↝, Fisetin also affected the activities of cytochrome P450 (CYP450 3A4) and glutathione-S-transferase
"highlight2" >GSTs↝,
"highlight2" >RadioS↑, fisetin pretreatment heightened the radiosensitivity of p53-mutant HT29 human CRC cells
"highlight2" >Inflam↓, Fisetin suppresses inflammation in the colon and CRC
"highlight2" >β-catenin/ZEB1↓, fisetin in treating colon cancer, revealing its capability to effectively downregulate β-catenin and COX-2
"highlight2" >EGFR↓, fisetin decreased EGFR and NF-κB activation in HT29 cells
"highlight2" >TumCCA↑, It induces cell cycle arrest, disrupting the transition from the G1 to the S phase, as well as causing G2/M phase arrest
"highlight2" >ChemoSen↑, intervention with fisetin and 5-FU appeared to extend the lifespan of the experimental animals

2853- FIS,    Fisetin Inhibits Cell Proliferation and Induces Apoptosis via JAK/STAT3 Signaling Pathways in Human Thyroid TPC 1 Cancer Cells
- in-vitro, Thyroid, TPC-1
"highlight2" >Apoptosis↑, fisetin stimulated apoptosis, which confirmed through reduced cell viability, improved ROS generation, altered MMP and cell cycle phases in TPC-1 cells.
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >TumCCA↑,
"highlight2" >Casp3↑, fisetin up-regulated the expression of caspase (3, 8, and 9) expressions in TPC-1 cells.
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >JAK1↓, fisetin down-regulated the JAK 1 and STAT3 expression in TPC1 cells
"highlight2" >STAT3↓,

1113- FIS,    Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >EMT↓,
"highlight2" >E-cadherin↑, A549
"highlight2" >ZO-1↑, h1299
"highlight2" >Vim↓,
"highlight2" >N-cadherin↓,
"highlight2" >MMP2↓,
"highlight2" >CD44↓,
"highlight2" >CD133↓,
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >NF-kB↓,
"highlight2" >EGFR↓,
"highlight2" >STAT3↓,

2855- FIS,    Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells
- in-vitro, RCC, Caki-1
"highlight2" >TumCCA↑, Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation.
"highlight2" >cl‑PARP↑,
"highlight2" >Apoptosis↑,
"highlight2" >Casp↑,
"highlight2" >P53↑, fisetin induced p53 protein expression
"highlight2" >DR5↑, fisetin-induced DR5 expression.
"highlight2" >CHOP↑, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis.
"highlight2" >ROS↑,
"highlight2" >ER Stress↑, Fisetin induced expression of ER stress-related proteins, including CHOP and activating ATF4
"highlight2" >ATF4↑,
"highlight2" >XBP-1↑, fisetin also increased the spliced form of the X-box binding protein (XBP)-1 mRNA
"highlight2" >eff∅, In our study, NAC did not enhance fisetin-induced apoptosis, and the ROS scavenger, GEE, also had no effect on apoptosi

2856- FIS,    N -acetyl- L -cysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells
- in-vitro, Colon, COLO205
"highlight2" >eff↑, We now demonstrate that 10 and 20 mM NAC, non-toxic concentrations, can enhance fisetin (FIS)-mediated apoptosis in colon cancer cells COLO205.
"highlight2" >ROS↑, N -acetyl- L -cysteine (NAC) enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis
"highlight2" >tumCV↓, FIS at the concentrations of 60 and 120 mM inhibited the viability of COLO205 colon carcinoma cell
"highlight2" >Casp3↑, induction of caspase 3 activation and reduction of Bcl-2 protein in accordance with a decreased MMP were detected in NAC + FIS-treated COLO205 cells.
"highlight2" >Bcl-2↓,
"highlight2" >MMP↓,
"highlight2" >eff↑, Enhancement of apoptosis by NAC was also observed in HT-29, HCT-116, and HCT-15 cells under FIS treatment, and in CHR-treated COLO205 cells.

2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
"highlight2" >COX2↓, fisetin altered the expression of cyclooxygenase 2 (COX2) thereby suppressed the secretion of prostaglandin E2 ultimately resulting in the inhibition of epidermal growth factor receptor (EGFR) and NF-κB in human colon cancer cells HT29
"highlight2" >PGE2↓,
"highlight2" >EGFR↓,
"highlight2" >Wnt↓, fisetin treatment inhibited the stimulation of Wnt signaling pathway via downregulating the expression of β-catenin and Tcell factor (TCF) 4
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >TCF↑,
"highlight2" >Apoptosis↑, fisetin triggers apoptosis in U266 cells through multiple pathways: enhancing the activation of caspase-3 and PARP cleavage, decreasing the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1 L ),
"highlight2" >Casp3↑,
"highlight2" >cl‑PARP↑,
"highlight2" >Bcl-2↓,
"highlight2" >Mcl-1↓,
"highlight2" >BAX↑, ncreasing the expression of pro-apoptotic proteins (Bax, Bim, and Bad)
"highlight2" >BIM↑,
"highlight2" >BAD↑,
"highlight2" >Akt↓, decreasing the phosphorylation of AKT and mTOR and elevating the expression of acetyl CoA carboxylase (ACC
"highlight2" >mTOR↓,
"highlight2" >ACC↑,
"highlight2" >Cyt‑c↑, release the cytochrome c and Smac/Diablo into the cytosol
"highlight2" >Diablo↑,
"highlight2" >cl‑Casp8↑, fisetin exhibited an increased level of cleaved caspase-8, Fas/Fas ligand, death receptor 5/TRAIL, and p53 levels in HCT-116 cells
"highlight2" >Fas↑,
"highlight2" >DR5↑,
"highlight2" >TRAIL↑,
"highlight2" >Securin↓, Securin gets degraded on exposure to fisetin in colon cancer cells.
"highlight2" >CDC2↓, fisetin decreased the expression of cell division cycle proteins (CDC2 and CDC25C)
"highlight2" >CDC25↓,
"highlight2" >HSP70/HSPA5↓, Fisetin induced apoptosis as a result of the downregulation of HSP70 and BAG3 and the inhibition of Bcl-2, Bcl-x L and Mcl-1. T
"highlight2" >CDK2↓, AGS 0, 25, 50, 75 μM – 24 and 48 h ↓CDK2, ↓CDK4, ↓cyclin D1, ↑casapse-3 cleavage
"highlight2" >CDK4↓,
"highlight2" >cycD1↓,
"highlight2" >MMP2↓, A549 0, 1, 5, 10 μM- 24 and 48 hr: ↓MMP-2, ↓u-PA, ↓NF- κB, ↓c-Fos, ↓c-Jun
"highlight2" >uPA↓,
"highlight2" >NF-kB↓,
"highlight2" >cFos↓,
"highlight2" >cJun↓,
"highlight2" >MEK↓, ↓ MEK1/2 and ERK1/2 phosphorylation, ↓N-cadherin, ↓vimentin, ↓snail, ↓fibronectin, ↑E-cadherin, ↑desmoglein
"highlight2" >p‑ERK↓,
"highlight2" >N-cadherin↓,
"highlight2" >Vim↓,
"highlight2" >Snail↓,
"highlight2" >Fibronectin↓,
"highlight2" >E-cadherin↓,
"highlight2" >NF-kB↑, increased expression of NF-κB p65 leading to apoptosis was due to ROS generation on exposure to fisetin
"highlight2" >ROS↑,
"highlight2" >DNAdam↑, increased ROS triggered cell death through PARP cleavage, DNA damage and mitochondrial membrane depolarization.
"highlight2" >MMP↓,
"highlight2" >CHOP↑, Though fisetin upregulated CHOP expression and increased the production of ROS, these events fail to induce apoptosis in Caki cells.
"highlight2" >eff↑, 50 μM fisetin + 1 mM melatonin Sk-mel-28 Enhances anti-tumour activity [54] 20 μM fisetin + 1 mM melatonin MeWo Enhances anti-tumour activity [54] 10 μM fisetin + 0.1 μM melatonin A549 Induces autophagic cell death
"highlight2" >ChemoSen↑, 20 μM fisetin + 5 μM sorafenib A375, SK-MEL-28 Suppresses invasion and metastasis [44] 40 μM fisetin + 10 μM cisplatin A549, A549-CR Enhances apoptosis

2858- FIS,    Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines
- in-vitro, BC, 4T1
"highlight2" >HO-1↑, fisetin increased HO-1 mRNA and protein expressions
"highlight2" >NRF2↑, fisetin also elevated Nrf2 expression in nuclear fraction
"highlight2" >MMP2↓, fisetin decreased MMP-2 and MMP-9 enzyme activity and gene expression in both protein and mRNA levels.
"highlight2" >MMP9↓,

2859- FIS,    The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways
- in-vitro, Liver, HepG2 - NA, Colon, Caco-2
"highlight2" >TumCG↓, fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines.
"highlight2" >other↝, activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.
"highlight2" >Casp3↑, Fisetin caused significant increase in activation of caspase 3/7 compared to untreated control
"highlight2" >Casp7↑,
"highlight2" >PGE2↓, Fisetin inhibits PGE2 production
"highlight2" >GSTs↓, GST enzyme activity assay has been carried out. The results showed that fisetin induced enzyme inhibition in a dose dependent manner
"highlight2" >Wnt↓, inhibiting Wnt/EGFR/NF-kB and COX-2 signaling pathways
"highlight2" >EGFR↓,
"highlight2" >NF-kB↓,
"highlight2" >COX2↓,
"highlight2" >P53↑, induction of p53 and p21
"highlight2" >P21↑,
"highlight2" >P450↓, Fisetin also was able to inhibit cyctochrome P450 (CYP450 3A4) and glutatihione -S-transferase activity

2860- FIS,    Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways
- in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3 - in-vitro, Nor, hTERT-HPNE - in-vivo, NA, NA
"highlight2" >AMPK↑, We found that the AMPK/mTOR signaling pathway was enhanced after fisetin treatment
"highlight2" >mTOR↑,
"highlight2" >UPR↑, RNA-seq analysis revealed that the unfolded protein response pathway, which is activated by ER stress, was enriched
"highlight2" >ER Stress↑, Fisetin induced ER stress in pancreatic cancer cells
"highlight2" >selectivity↑, results showed that fisetin was less cytotoxic to normal cells compared with pancreatic cancer cells
"highlight2" >TumCP↓, fisetin inhibited the proliferation of PANC-1 cells
"highlight2" >PERK↑, expression of PERK, ATF4, and ATF6 were also upregulated by fisetin
"highlight2" >ATF4↑,
"highlight2" >ATF6↑,

2861- FIS,    The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress
- Review, Nor, NA - Review, Stroke, NA - Review, Park, NA
"highlight2" >*antiOx↑, Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS
"highlight2" >*ROS↓, The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders.
"highlight2" >*neuroP↑,
"highlight2" >*NO↑, inhibits NO production.
"highlight2" >BioAv↝, oral bioavailability of fisetin was reported 7.8 and 31.7% for oral doses of 100 and 200 mg/kg, respectively
"highlight2" >*BBB↑, BBB permeability, fisetin can also affect hippocampal synaptic plasticity indirectly through the peripheral system
"highlight2" >*toxicity↑, Furthermore, it did not show signs of toxicity at doses up to 2 g/kg in an acute toxicity study with no toxicity in the histopathological analysis of the heart, lungs, kidneys, liver, stomach, intestines, spleen and reproductive organs
"highlight2" >*eff↑, potential benefits against neurological health complications and neurodegenerative diseases like AD, PD. HD, ALS, vascular dementia, schizophrenia, stroke, depression, diabetic neuropathy and traumatic brain injury
"highlight2" >*GSH↑, direct antioxidant activity in addition to increasing intracellular antioxidants such as glutathione
"highlight2" >*SOD↑, fig 2
"highlight2" >*Aβ↓,
"highlight2" >*12LOX↓,
"highlight2" >*COX2↓,
"highlight2" >*Catalase↑, Fisetin treatment prevented behavioral deficits, increased brain antioxidant, superoxide dismutase, catalase, reduced glutathione, and BDNF
"highlight2" >*Inflam↓, decreased serum homocysteine, and pro-inflammatory biomarkers (TNF-α, IL-6), lipid peroxidation
"highlight2" >*TNF-α↓,
"highlight2" >*IL6↑,
"highlight2" >*lipid-P↓,
"highlight2" >NF-kB↓, suppressed the up-regulation of NF-κB, and IDO-1 genes expression, and decreased the rise of IL-1β levels.
"highlight2" >IL1β↓,
"highlight2" >NRF2↑, fisetin treatment also restored the downregulation of Nrf-2, HO-1, and ChAT genes expression and BDNF levels in the hippocampus, suggesting its protective effect against oxidative stress
"highlight2" >HO-1↑,
"highlight2" >GSTs↑, Fisetin also restored the AlCl3-induced reduction in the levels of SOD, CAT, GST, and GSH in a study that analysed the effect of this compound on AlCl3-induced reactive gliosis and neuronal inflammation in the brain of mice
"highlight2" >cognitive↑, Fisetin improves neurodegenerative disease-associated dementia, cognitive functions and behavioral abnormalities along with increasing age
"highlight2" >*BDNF↑, Fisetin also increases BDNF activity to prevent neurodegeneration

2862- FIS,    Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rat
- in-vivo, Diabetic, NA
"highlight2" >*BG↓, Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin
"highlight2" >*NF-kB↓,
"highlight2" >*IL1β↓,
"highlight2" >*NO↓,
"highlight2" >*Insulin↑,
"highlight2" >*SOD↑, Furthermore, the levels of activities of enzymatic antioxidants such as SOD, CAT, GPx, and GST were significantly improved in fisetin treated diabetic rats.
"highlight2" >*Catalase↑,
"highlight2" >*GPx↑,
"highlight2" >*GSTs↑,

2843- FIS,    Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential
- Review, Var, NA
"highlight2" >NRF2↑, fisetin increased the protein level and accumulation Nrf2 and down regulated the protein levels of Keap1
"highlight2" >Keap1↓,
"highlight2" >ChemoSen↑, In vitro studies showed that fisetin and quercetin could also act against chemotherapeutic resistance in several cancers
"highlight2" >BioAv↓, Fisetin has low aqueous solubility and bioavailability
"highlight2" >Cyt‑c↑, release of cytochrome c from mitochondria, caspase-3 and caspase-9 mRNA and protein expression, and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels, were found to be regulated in the fisetin-treated cancer cell line
"highlight2" >Casp3↑,
"highlight2" >Casp9↑,
"highlight2" >BAX↑,
"highlight2" >tumCV↓, fisetin at 5–80 µM significantly reduced the viability of A431 human epidermoid carcinoma cells by the release of cytochrome c,
"highlight2" >Mcl-1↓, reducing the anti-apoptotic protein expression of Bcl-2, Bcl-xL, and Mcl-1 along with elevation of pro-apoptotic protein expression (Bax, Bak, and Bad) and caspase cleavage and poly-ADP-ribose polymerase (PARP) protein
"highlight2" >cl‑PARP↑,
"highlight2" >IGF-1↓, fisetin promoted caspase-8 and cytochrome c expression, possibly by impeding the aberrant activation of insulin growth factor receptor 1 and Akt
"highlight2" >Akt↓,
"highlight2" >CDK6↓, fisetin binds with CDK6, which in turn blocks its activity with an inhibitory concentration (IC50) at a concentration of 0.85 μM
"highlight2" >TumCCA↑, fisetin is identified as a regulator of cell cycle checkpoints, leading to cell arrest through CDK inhibition in HL60 cells and astrocyte cells over the G0/G1, S, and G2/M phases
"highlight2" >P53?, exhibiting elevated levels of p53
"highlight2" >cycD1↓, 10–60 μM fisetin concentration, prostate cancer cells PC3, LNCaP, and CWR22Ry1 had decreased cellular viability and decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
"highlight2" >cycE↓,
"highlight2" >CDK2↓, decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,
"highlight2" >MMP2↓, fisetin displayed tumor inhibitory effects by blocking MMP-2 and MMP-9 at mRNA and protein levels in prostate PC-3 cells
"highlight2" >MMP9↓,
"highlight2" >MMP1↓, Similarly, fisetin can also inhibit MMP-1, MMP-9, MMP-7, MMP-3, and MMP-14 gene expression linked with ECM remodeling in human umbilical vascular endothelial cells (HUVECs) and HT-1080 fibrosarcoma cells [9
"highlight2" >MMP7↓,
"highlight2" >MMP3↓,
"highlight2" >VEGF↓, fisetin in a concentration-dependent manner (10–50 μM concentration) significantly inhibited regular serum, growth-enhancing supplement, and vascular endothelial growth factor (VEGF)
"highlight2" >PI3K↓, fisetin inhibited PI3K expression and phosphorylation of Akt
"highlight2" >mTOR↓, fisetin treatment activated the apoptotic process through inhibiting both PI3K and mammalian target of rapamycin (mTOR) signaling pathways
"highlight2" >COX2↓, fisetin resulted in activation of apoptosis and inhibition of COX-2 and the Wnt/EGFR/NF-kB pathway
"highlight2" >Wnt↓,
"highlight2" >EGFR↓,
"highlight2" >NF-kB↓,
"highlight2" >ERK↓, Fisetin is one of the flavonoids that has been found to suppress ERK1/2 signaling in human gastric (SGC7901), hepatic (HepG2), colorectal (Caco-2)
"highlight2" >ROS↑, fisetin induced ROS generation and suppressed ERK through its phosphorylation
"highlight2" >angioG↓, fisetin-induced anti-angiogenesis led to reduced VEGF and epidermal growth factor receptor (EGFR) expression
"highlight2" >TNF-α↓, Fisetin suppressed IL-1β-mediated expression of inducible nitric oxide synthase, nitric oxide, interleukin-6, tumor necrotic factor-α, prostaglandin E2, cyclooxygenase-2 (iNOS, NO, IL-6, TNF-α, PGE2, and COX-2),
"highlight2" >PGE2↓,
"highlight2" >iNOS↓,
"highlight2" >NO↓,
"highlight2" >IL6↓,
"highlight2" >HSP70/HSPA5↝, fisetin-mediated inhibition of cellular proliferation by HSP70 and HSP27 regulation
"highlight2" >HSP27↝,

949- FIS,  ATAGJ,  Cisplatin,    Ai-Tong-An-Gao-Ji and Fisetin Inhibit Tumor Cell Growth in Rat CIBP Models by Inhibiting the AKT/HIF-1α Signaling Pathway
- in-vivo, BC, Walker256 - in-vitro, BC, Walker256
"highlight2" >Akt↓,
"highlight2" >Hif1a↓,
"highlight2" >p‑Akt↓,

2824- FIS,    Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics
- Review, Var, NA
"highlight2" >*antiOx↑, Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, i.e., antioxidant, anti-inflammatory, antiangiogenic, and anticancer properties.
"highlight2" >*Inflam↓,
"highlight2" >angioG↓,
"highlight2" >BioAv↓, poor bioavailability associated with its extreme hydrophobicity hampers its clinical utility
"highlight2" >BioAv↑, The issues related to fisetin delivery can be addressed by adapting to the developmental aspects of nanomedicines, such as formulating it into lipid or polymer-based systems, including nanocochleates and liposomes
"highlight2" >TumCP↓, fisetin also inhibits tumor proliferation by repressing tumor mass multiplication, invasion, migration, and autophagy.
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >*neuroP↑, figure 2
"highlight2" >EMT↓, It affects the cell cycle and thereby cell proliferation, microtubule assembly, cell migration and invasion, epithelial to mesenchymal transition (EMT), and cell death
"highlight2" >ROS↑, cell death caused by fisetin is possibly due to the induction of apoptosis by fisetin or other signaling molecules and reactive oxygen species (ROS)
"highlight2" >selectivity↑, Without influencing the growth of normal cells, fisetin has the capability to hinder the formation of colonies and inhibit the multiplication of cancer cells.
"highlight2" >EGFR↓, fisetin restricts the multiplication of EGFR 2-overexpressing SK-BR-3 breast tumor masses
"highlight2" >NF-kB↓, fisetin inhibits cancer metastasis by reducing the expressions of nuclear factor-kB (NF-kB)-modulated metastatic proteins in a variety of tumor cell types, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP)
"highlight2" >VEGF↓,
"highlight2" >MMP9↓,
"highlight2" >MMP↓, rupturing the plasma membrane, depolarizing mitochondria, cleaving PARP, and activating caspase-7, -8, and -9.
"highlight2" >cl‑PARP↑,
"highlight2" >Casp7↑,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >*ROS↓, Fisetin is a bioactive flavonol molecule that can easily penetrate the cell membrane due to its hydrophobic nature [51,52], reducing the generation of inflammatory cytokines and reactive oxygen species (ROS) in microglial cells, (normal cells)
"highlight2" >uPA↓, Perhaps fisetin lowers angiogenesis, consequently suppressing tumor multiplication by urokinase plasminogen activator (uPA) inhibition
"highlight2" >MMP1↓, powerful matrix metalloproteinase (MMP)-1 inhibitor
"highlight2" >Wnt↓, Fisetin works on several cellular pathways, such as Wnt, Akt-PI3K, and ERK, as an inhibitor
"highlight2" >Akt↓,
"highlight2" >PI3K↓,
"highlight2" >ERK↓,
"highlight2" >Half-Life↝, Fisetin exhibits a very short terminal half-life of approximately 3 hrs in its free form. This half-life is found to be less than that of its metabolites

2825- FIS,    Exploring the molecular targets of dietary flavonoid fisetin in cancer
- Review, Var, NA
"highlight2" >*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
"highlight2" >*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
"highlight2" >*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
"highlight2" >*p‑cMyc↑,
"highlight2" >*NRF2↑,
"highlight2" >*GSH↑,
"highlight2" >*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
"highlight2" >mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
"highlight2" >cycD1↓,
"highlight2" >cycE↓,
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,
"highlight2" >P21↑,
"highlight2" >p27↑,
"highlight2" >JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
"highlight2" >NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
"highlight2" >cFos↓,
"highlight2" >cJun↓,
"highlight2" >E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
"highlight2" >Vim↓,
"highlight2" >N-cadherin↓,
"highlight2" >EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
"highlight2" >MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
"highlight2" >Cyt‑c↑,
"highlight2" >Diablo↑,
"highlight2" >Casp↑,
"highlight2" >cl‑PARP↑,
"highlight2" >P53↑, fisetin with induction of p53 protein
"highlight2" >COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
"highlight2" >PGE2↓,
"highlight2" >HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
"highlight2" >HSP27↓,
"highlight2" >DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
"highlight2" >Casp3↑,
"highlight2" >Casp9↑,
"highlight2" >ROS↑, This was associated with production of intracellular ROS
"highlight2" >AMPK↑, Fisetin induced AMPK signaling
"highlight2" >NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
"highlight2" >Ca+2↑,
"highlight2" >mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
"highlight2" >p70S6↓,
"highlight2" >ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
"highlight2" >ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
"highlight2" >IRE1↑,
"highlight2" >ATF4↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
"highlight2" >eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
"highlight2" >eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
"highlight2" >RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
"highlight2" >ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
"highlight2" >Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h.

2826- FIS,    Fisetin induces apoptosis in breast cancer MDA-MB-453 cells through degradation of HER2/neu and via the PI3K/Akt pathway
- in-vitro, BC, MDA-MB-453
"highlight2" >Apoptosis↑, fisetin induced apoptosis of these cells by various mechanisms, such as inactivation of the receptor, induction of proteasomal degradation, decreasing its half-life, decreasing enolase phosphorylation, and alteration of PI3K/AKT
"highlight2" >p‑ENO1↓,
"highlight2" >DNAdam↑, displaying DNA fragmentation pattern
"highlight2" >PI3K↑, Fisetin increased PI3K activity at 10 uM, which gradually declines on treatment with higher concentrations (25 or 50 uM)
"highlight2" >p‑Akt↑, Fisetin (10 uM) increased phosphorylation of Akt in MDA-MB-453 cells greater than control. Higher concentrations of fisetin (25 or 50 uM) gradually decreased the phosphorylation of Akt.
"highlight2" >HER2/EBBR2↓, fisetin induced HER2 depletion

2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
"highlight2" >*antiOx↑, effective antioxidant, anti-inflammatory
"highlight2" >*Inflam↓,
"highlight2" >neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
"highlight2" >hepatoP↑,
"highlight2" >RenoP↑,
"highlight2" >cycD1↓, Figure 3
"highlight2" >TumCCA↑,
"highlight2" >MMPs↓,
"highlight2" >VEGF↓,
"highlight2" >MAPK↓,
"highlight2" >NF-kB↓,
"highlight2" >angioG↓,
"highlight2" >Beclin-1↑,
"highlight2" >LC3s↑,
"highlight2" >ATG5↑,
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,
"highlight2" >Casp↑,
"highlight2" >TNF-α↓,
"highlight2" >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,
"highlight2" >MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
"highlight2" >mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
"highlight2" >cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
"highlight2" >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
"highlight2" >CDK4↓,
"highlight2" >Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
"highlight2" >Diablo↑,
"highlight2" >DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
"highlight2" >Fas↑,
"highlight2" >PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
"highlight2" >Ki-67↓,
"highlight2" >p‑H3↓,
"highlight2" >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.
"highlight2" >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.
"highlight2" >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
"highlight2" >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
"highlight2" >CDC2↓,
"highlight2" >CHK1↑,
"highlight2" >Chk2↑,
"highlight2" >ATM↑,
"highlight2" >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
"highlight2" >RAS↓,
"highlight2" >p‑p38↓,
"highlight2" >Rho↓,
"highlight2" >uPA↓,
"highlight2" >MMP7↓,
"highlight2" >MMP13↓,
"highlight2" >GSK‐3β↑,
"highlight2" >E-cadherin↑,
"highlight2" >survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
"highlight2" >VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
"highlight2" >IAP2↓, The downregulation of cIAP-2 by fisetin
"highlight2" >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
"highlight2" >JAK1↓,
"highlight2" >mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
"highlight2" >mTORC2↓,
"highlight2" >NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

2828- FIS,    Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review
- Review, Var, NA
"highlight2" >*neuroP↑, As a hydrophobic agent, FIS readily penetrates cell membranes and accumulates in cells to exert neuroprotective, neurotrophic and antioxidant effects
"highlight2" >*antiOx↑,
"highlight2" >*Inflam↓, FIS treatment may include alleviating inflammation, cell apoptosis and oxidative stress
"highlight2" >RenoP↑, alleviates cell apoptosis and inflammation in acute kidney injury
"highlight2" >COX2↓, FIS induces apoptosis in various tumor cells by, for example, inhibiting cyclooxygenase-2, inhibiting the Wnt/EGFR/NF-κB pathway, activating the caspase-3 cascade
"highlight2" >Wnt↓,
"highlight2" >EGFR↓,
"highlight2" >NF-kB↓,
"highlight2" >Casp3↑,
"highlight2" >Ca+2↑, activating the caspase-3 and Ca2+ dependent endonuclease, and activating the caspase-8/caspase-3 dependent pathway via ERK1/2.
"highlight2" >Casp8↑,
"highlight2" >TumCCA↑, FIS controls the cell cycle and inhibits cyclin-dependent kinases (CDKs) in human cancer cell lines,
"highlight2" >CDK1↓,
"highlight2" >PI3K↓, by inhibition of PI3K/Akt/mTOR signaling [20], mitogen-activated protein kinases (MAPK) [21], and nuclear transcription factor (NF-κB)
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >MAPK↓,
"highlight2" >*P53↓, FIS inhibits aging by reducing p53, p21 and p16 expression in mouse and human tissues
"highlight2" >*P21↓,
"highlight2" >*p16↓,
"highlight2" >mTORC1↓, FIS induces autophagic cell death by inhibiting both the mTORC1 and mTORC2 pathways
"highlight2" >mTORC2↓,
"highlight2" >P53↑, FIS significantly increases the expression of p53 and p21 proteins and lowers the levels of cyclin D1 [27,28], cyclin A, CDK4 and CDK2, thus contributing to cell-cycle arrest.
"highlight2" >P21↑,
"highlight2" >cycD1↓,
"highlight2" >cycA1↓,
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >BAX↑, FIS also increases Bax [27,28] and Bak [27] protein expression, but reduces the levels of Bcl-2 [27,28], Bcl-xL [27] and PCNA [28], and then starts the mitochondrial apoptotic pathway.
"highlight2" >Bcl-2↓,
"highlight2" >PCNA↓,
"highlight2" >HER2/EBBR2↓, FIS reduces HER2 tyrosine phosphorylation in a dose-dependent manner and aids in proteasomal degradation of HER2 rather than lysosomal degradation
"highlight2" >Cyt‑c↑, FIS cells causes destabilization of the mitochondrial membrane and an increase in cytochrome c levels, which is consistent with the loss of mitochondrial membrane integrity.
"highlight2" >MMP↓,
"highlight2" >cl‑Casp9↑,
"highlight2" >MMP2↓, FIS reduces the enzymatic activity of both MMP-2 and MMP-9.
"highlight2" >MMP9↓,
"highlight2" >cl‑PARP↑, cell membrane, mitochondrial depolarization, activation of caspase-7, -8 and -9, and cleavage of PARP
"highlight2" >uPA↓, interestingly, the promoter activity of the uPA gene is suppressed by FIS
"highlight2" >DR4↑, induces upregulation of DR4 and DR5 death receptor expression in a dose-dependent manner
"highlight2" >DR5↑,
"highlight2" >ROS↓, FIS induces an increase in intracellular Ca2+ but reduces the production of ROS in WEHI-3 cells (myelomonocytic leukemia)
"highlight2" >AIF↑, It also increases the levels of caspase-3 and AIF mRNA, but also increases necrosis markers including RIP3 and PARP1
"highlight2" >CDC25↓, FIS reduces the expression of cdc25a, but increases the expression of p-p53, Chk1, p21 and p27, which may lead to a G0/G1 arrest.
"highlight2" >Dose↑, FIS in concentrations from 0 to 10 μM does not affect cell viability; however, its use at concentrations of 20–40 μM significantly reduces the viability of lung cancer cells
"highlight2" >CHOP↑, CaKi : FIS induces upregulation of CHOP expression and ROS production
"highlight2" >ROS↑, NCI-H460 :FIS increases the ER stress signaling FIS increases the level of mitochondrial ROS FIS induces mitochondrial Ca2+ overloading and ER stress FIS induced ER stress-mediated cell death via activation of the MAPK pathway
"highlight2" >cMyc↓, FIS influences proliferation related genes such as cyclin D1, c-myc and cyclooxygenase (COX)-2 by downregulating them.
"highlight2" >cardioP↑, cardioprotective activity

2829- FIS,    Fisetin: An anticancer perspective
- Review, Var, NA
"highlight2" >TumCP↓, Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage
"highlight2" >TumCI↓,
"highlight2" >TumCCA↑,
"highlight2" >TumCG↓,
"highlight2" >Apoptosis↑,
"highlight2" >cl‑PARP↑,
"highlight2" >PKCδ↓, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin
"highlight2" >ROS↓,
"highlight2" >ERK↓,
"highlight2" >NF-kB↓,
"highlight2" >survivin↓,
"highlight2" >ROS↑, In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis
"highlight2" >PI3K↓, Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >MAPK↓, phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively,
"highlight2" >p38↓,
"highlight2" >HER2/EBBR2↓, (HER2)/neu‐overexpressing breast cancer cell lines. Fisetin caused induction through inactivating the receptor, inducing the degradation of the proteasomes, reducing its half‐life
"highlight2" >EMT↓, In addition, mutation of epithelial‐to‐mesenchymal transition (EMT)
"highlight2" >PTEN↑, up‐regulation of expression of PTEN mRNA and protein were reported after fisetin treatment
"highlight2" >HO-1↑, In breast cancer cells (4T1 and JC cells), fisetin increased HO‐1 mRNA and protein expressions, elevated Nrf2 expression
"highlight2" >NRF2↑,
"highlight2" >MMP2↓, fisetin reduced MMP‐2 and MMP‐9 enzyme activity and gene expression for both mRNA levels and protein
"highlight2" >MMP9↓,
"highlight2" >MMP↓, fisetin treatment further led to permeabilization of mitochondrial membrane, activation of caspase‐8 and caspase‐9, as well as the cleavage of poly(ADP‐ribose) polymerase 1
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >TRAILR↑, enhanced the levels of TRAIL‐R1
"highlight2" >Cyt‑c↑, mitochondrial releasing of cytochrome c into cytosol, up‐regulation and down‐regulation of X‐linked inhibitor of apoptosis protein
"highlight2" >XIAP↓,
"highlight2" >P53↑, fisetin also enhanced the protein p53 levels
"highlight2" >CDK2↓, lowered cell number, the activities of CDK‐2,4)
"highlight2" >CDK4↓,
"highlight2" >CDC25↓, it also decreased cell division cycle protein levels (CDC)2 and CDC25C, and CDC2 activity (Lu et al., 2005)
"highlight2" >CDC2↓,
"highlight2" >VEGF↓, down‐regulating the expressions of p‐ERK1/2, vascular endothelial growth factor receptor 1(VEGFR1), p38, and pJNK, respectively
"highlight2" >DNAdam↑, Fisetin (80 microM) showed dose‐dependently caused DNA fragmentation, induced cellular swelling and apoptotic death, and showed characteristics of apoptosis.
"highlight2" >TET1↓, lowered the TET1 expression levels
"highlight2" >CHOP↑, caused up‐regulation of (C/EBP) homologous protein (CHOP) expression and reactive oxygen species production,
"highlight2" >CD44↓, down‐regulation of CD44 and CD133 markers
"highlight2" >CD133↓,
"highlight2" >uPA↓, down‐regulation of levels of matrix metalloproteinase‐2 (MMP‐2), urokinase‐type plasminogen activator (uPA),

2830- FIS,    Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent
- Review, Var, NA
"highlight2" >TumCG↓, suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration.
"highlight2" >angioG↓,
"highlight2" >*ROS↓,
"highlight2" >TumCMig↓,
"highlight2" >VEGF↓, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1.
"highlight2" >MAPK↑, including the activation of MAPK. activation of MAPK is crucial for mediating cancer cell proliferation, apoptosis, and invasion
"highlight2" >NF-kB↓, ability of fisetin to suppress NF-κB activity has been demonstrated in various diseases
"highlight2" >PI3K↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT
"highlight2" >Akt↓,
"highlight2" >mTOR↓, Fisetin has been shown to be effective against PI3K expression, AKT phosphorylation, and mTOR activation in various cancer cells,
"highlight2" >NRF2↑, effects of fisetin on the activation of Nrf2 and upregulation of HO-1 have been demonstrated in various diseases
"highlight2" >HO-1↑,
"highlight2" >ROS↓, Liver cancer Resist proliferation, migration and invasion, induce apoptosis, attenuate ROS and inflammation
"highlight2" >Inflam↓,
"highlight2" >ER Stress↑, Oral cancer Induce apoptosis and autophagy, promote ER stress and ROS, suppress proliferation
"highlight2" >ROS↑, Multiple studies have demonstrated that fisetin has the ability to induce apoptosis in cancer cells, and various mechanisms are involved, including the activation of MAPK, NF-κB, p53, and the generation of reactive oxygen species (ROS)
"highlight2" >TumCP↓,
"highlight2" >ChemoSen↑, Breast cancer Promote apoptosis and invasion and metastasis, enhance chemotherapeutic effects
"highlight2" >PTEN↑,
"highlight2" >P53↑, activation of MAPK, NF-κB, p53,
"highlight2" >Casp3↑,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >COX2↓, fisetin inhibits COX2 expression
"highlight2" >Wnt↓, regulating a number of important angiogenesis-related factors in cancer cells, such as VEGF, MMP2/9, eNOS, wingless and Wnt-signaling.
"highlight2" >EGFR↓,
"highlight2" >Mcl-1↓,
"highlight2" >survivin↓, fisetin interferes with NF-κB signaling, resulting in the reduction of survivin, TRAF1, Bcl-xl, Bcl-2, and IAP1/2 levels, ultimately inhibiting apoptosis
"highlight2" >IAP1↓,
"highlight2" >IAP2↓,
"highlight2" >PGE2↓, fisetin inhibits COX2 expression, leading to the down-regulation of PGE2 secretion and inactivation of β-catenin, thereby inducing apoptosis
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >DR5↑, fisetin markedly induces apoptosis in renal carcinoma through increased expression of DR5, which is regulated by p53.
"highlight2" >MMP2↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT and JNK pathways, resulting in the suppression of MMP-2 and MMP-9 expression
"highlight2" >MMP9↓,
"highlight2" >FAK↓, fisetin can inhibit cell migration and reduce focal adhesion kinase (FAK) phosphorylation levels
"highlight2" >uPA↓, fisetin significantly suppresses the invasion of U-2 cells by decreasing the expression of NF-κB, urokinase-type plasminogen activator (uPA), FAK, and MMP-2/9
"highlight2" >EMT↓, Fisetin has been shown to have the ability to reverse EMT, thereby inhibiting the invasion and migration of cancer cells
"highlight2" >ERK↓, fisetin has the ability to suppress ERK1/2 activation and activate JNK/p38 pathways
"highlight2" >JNK↑,
"highlight2" >p38↑,
"highlight2" >PKCδ↓, fisetin reduces the expression of MMP-9 by inhibiting PKCα/ROS/ERK1/2 and p38 MAPK activation
"highlight2" >BioAv↓, low water solubility of fisetin poses a significant challenge for its administration, which can limit its biological effects
"highlight2" >BioAv↑, Compared to free fisetin, fisetin nanoemulsion has demonstrated a 3.9-fold increase in the generation of reactive oxygen species (ROS) and induction of apoptosis, highlighting its enhanced efficacy
"highlight2" >BioAv↑, Liposomal encapsulation has shown potential in enhancing the anticancer therapeutic effects of fisetin

2831- FIS,    Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy
- Review, Var, NA
"highlight2" >TumCG↓, Fisetin has shown the ability to suppress tumor growth and metastasis by modulating critical signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK.
"highlight2" >ER Stress↑, It induces apoptosis in cancer cells through mitochondrial and endoplasmic reticulum stress responses and demonstrates antioxidative properties by reducing reactive oxygen species.
"highlight2" >antiOx↓,
"highlight2" >ROS↓,
"highlight2" >ChemoSen↑, Additionally, fisetin enhances the efficacy of conventional chemotherapies, indicating its role as a potential adjuvant in cancer treatment.

2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
"highlight2" >MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
"highlight2" >mtDam↑,
"highlight2" >Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
"highlight2" >Diablo↑,
"highlight2" >Casp↑,
"highlight2" >cl‑PARP↑,
"highlight2" >Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
"highlight2" >BIM↑,
"highlight2" >Bcl-xL↓,
"highlight2" >Bcl-2↓,
"highlight2" >P53↑, fisetin through the activation of p53
"highlight2" >ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
"highlight2" >AMPK↑,
"highlight2" >Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
"highlight2" >Casp3↑,
"highlight2" >BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
"highlight2" >AIF↑,
"highlight2" >Akt↓, The inhibition of the Akt/mTOR/MAPK/
"highlight2" >mTOR↓,
"highlight2" >MAPK↓,
"highlight2" >Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
"highlight2" >P21↑,
"highlight2" >p27↑,
"highlight2" >cycD1↓,
"highlight2" >cycE↓,
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,
"highlight2" >TumMeta↓, reduces PC-3 cells' capacity for metastasis
"highlight2" >uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
"highlight2" >E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
"highlight2" >Vim↓,
"highlight2" >EMT↓,
"highlight2" >Twist↓,
"highlight2" >DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
"highlight2" >ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
"highlight2" >COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
"highlight2" >PGE2↓,
"highlight2" >HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
"highlight2" >cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
"highlight2" >cJun↓,
"highlight2" >AP-1↓,
"highlight2" >Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
"highlight2" >NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
"highlight2" >IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
"highlight2" >ER Stress↑,
"highlight2" >ATF4↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
"highlight2" >MMP9↓,
"highlight2" >TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
"highlight2" >MMP7↓,
"highlight2" >RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
"highlight2" >TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
"highlight2" >TOP2↓,

2833- FIS,  SNP,    Glucose-capped fisetin silver nanoparticles induced cytotoxicity and ferroptosis in breast cancer cells: A molecular perspective
- in-vitro, BC, MDA-MB-231
"highlight2" >MMP↓, MDA-MB-231 cells treated with glucose-capped fisetin silver nanoparticles showed signs of apoptosis, decreased mitochondrial membrane potential, and elevated Reactive oxygen species (ROS) production.
"highlight2" >ROS↑,
"highlight2" >NRF2↑, upregulation of SLC7A11, SLC40A1, NRF2F, NOX2, and NOX5 genes that are associated with various crucial cellular events
"highlight2" >NOX↑,
"highlight2" >selectivity↑, Glucose nanoparticles selectively deliver cytotoxic agents to cancer cells by targeting the glucose transporters overexpressed in cancer cells, resulting in minimal toxicity to healthy tissues

2838- FIS,    Fisetin induces apoptosis in colorectal cancer cells by suppressing autophagy and down-regulating nuclear factor erythroid 2-related factor 2 (Nrf2)
"highlight2" >cl‑Casp3↑, enhanced signals for the cleaved caspase 3 and nuclear PARP-1 in those fisetin-treated cells
"highlight2" >cl‑PARP↑,
"highlight2" >MMP↓, This was consistent with the collapse of mitochondrial membrane potential and release of cytochrome c
"highlight2" >Cyt‑c↑,
"highlight2" >ROS↑, fisetin-treated cells showed increased ROS level
"highlight2" >NRF2↓, and a significant decline in nuclear Nrf2 immunosignal versus recovery in nuclear Nrf2 due to the treatment with curcumin and resveratrol (Nrf2 activators) and thus, suggesting a role of Nrf2 suppression in fisetin-mediated apoptosis in SW-480 cells.

2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
"highlight2" >DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
"highlight2" >ROS↑,
"highlight2" >Apoptosis↑,
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,
"highlight2" >cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
"highlight2" >cl‑Casp3↑,
"highlight2" >Cyt‑c↑, leading to cytochrome-c release
"highlight2" >lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
"highlight2" >TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
"highlight2" >TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >uPA↓,
"highlight2" >ERK↓,
"highlight2" >MMP9↓,
"highlight2" >NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
"highlight2" >cFos↓,
"highlight2" >cJun↓,
"highlight2" >AP-1↓,
"highlight2" >TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
"highlight2" >AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
"highlight2" >mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
"highlight2" >mTORC2↓,
"highlight2" >TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
"highlight2" >EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
"highlight2" >TGF-β↓,
"highlight2" >EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
"highlight2" >P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
"highlight2" >PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
"highlight2" >Akt↓,
"highlight2" >mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
"highlight2" >eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
"highlight2" >ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
"highlight2" >ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
"highlight2" >IRE1↑,
"highlight2" >ATF4↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
"highlight2" >CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
"highlight2" >CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
"highlight2" >cycE↓,
"highlight2" >cycD1↓,
"highlight2" >P21↑,
"highlight2" >COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
"highlight2" >Wnt↓,
"highlight2" >EGFR↓,
"highlight2" >β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
"highlight2" >TCF-4↓,
"highlight2" >MMP7↓,
"highlight2" >RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
"highlight2" >eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells

2840- FIS,    Fisetin-induced cell death, apoptosis, and antimigratory effects in cholangiocarcinoma cells
- NA, CCA, NA
"highlight2" >ROS↑, The mechanism of cell death and apoptosis was measured by reactive oxygen species (ROS) generation
"highlight2" >TumCMig↓, Fisetin may inhibit cholangiocarcinoma (CCA) cell migration and proliferation;
"highlight2" >TumCP↓,

2841- FIS,    Fisetin, an Anti-Inflammatory Agent, Overcomes Radioresistance by Activating the PERK-ATF4-CHOP Axis in Liver Cancer
- in-vitro, Nor, RAW264.7 - in-vitro, Liver, HepG2 - in-vitro, Liver, Hep3B - in-vitro, Liver, HUH7
"highlight2" >*Inflam↓, fisetin reduced the LPS-induced production of pro-inflammation markers, such as TNF-α, IL-1β, and IL-6, demonstrating the anti-inflammatory effects of fisetin
"highlight2" >*TNF-α↓,
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >Apoptosis↓, fisetin induced apoptotic cell death and ER stress through intracellular calcium (Ca2+) release, the PERK-ATF4-CHOP signaling pathway, and induction of GRP78 exosomes.
"highlight2" >ER Stress↑,
"highlight2" >Ca+2↑,
"highlight2" >PERK↑, inducing the GRP78-PERK-ATF4-CHOP pathway in fisetin-treated radioresistant liver cancer cells.
"highlight2" >ATF4↑, fisetin treatment of HepG2 and Hep3B cells resulted in the upregulation of ATF4 and CHOP in a time-dependent manner
"highlight2" >CHOP↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >tumCV↓, fisetin decreased the cell viability and increased LDH activity in HepG2, Hep3B, and Huh7 cells in a concentration-dependent manner
"highlight2" >LDH↑,
"highlight2" >Casp3↑, caspase-3 activity was significantly enhanced
"highlight2" >cl‑Casp3↑, fisetin treatment significantly increased the pro-apoptotic markers, including cleaved caspase-3, caspase-8, and caspase-9
"highlight2" >cl‑Casp8↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >p‑eIF2α↑, fisetin treatment increased CHOP, p-eIF2α, ATF4, p-PERK, and GRP78 levels
"highlight2" >RadioS↑, Radiation Combined with Fisetin Overcomes Radioresistance

2842- FIS,    Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells
- in-vitro, GC, AGS
"highlight2" >TumCCA↑, Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells.
"highlight2" >CDK2↓,
"highlight2" >P53↑,
"highlight2" >selectivity↑, observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin
"highlight2" >MMP↓, Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells
"highlight2" >DNAdam↑, DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP
"highlight2" >cl‑PARP↑,
"highlight2" >mt-ROS↑, showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion
"highlight2" >eff↓, Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage
"highlight2" >survivin↓, We observed a decrease in the levels of survivin by fisetin in gastric cancer cells which further strengthens our results that fisetin decreases antiapoptotic proteins to promote apoptosis.

2844- FIS,    Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells
- in-vitro, OS, U2OS
"highlight2" >tumCV↓, Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by signifi-cantly inducing the expression of Caspases- 3,-8 and -9 and pro-apoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2
"highlight2" >Apoptosis↑,
"highlight2" >Casp3↑,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >BAX↑,
"highlight2" >BAD↑,
"highlight2" >Bcl-2↓,
"highlight2" >Bcl-xL↓,
"highlight2" >PI3K↓, inhibited PI3K/Akt pathway and ERK1/2,
"highlight2" >Akt↓,
"highlight2" >ERK↓,
"highlight2" >p‑JNK↑, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38
"highlight2" >p‑cJun↑,
"highlight2" >p‑p38↑,
"highlight2" >ROS↑, Fisetin-induced ROS generation and decrease in mitochondrial membrane potential
"highlight2" >MMP↓, noticeable decline of mitochondrial transmembrane potential (ΔΨm) in a dose-dependent manner
"highlight2" >mTORC1↓, fisetin at various concentrations (20-100 μM) caused a significant (p<0.05) decrease in the level of p-Akt and mTORC1 (an important effector protein of Akt), while up-regulated PTEN.
"highlight2" >PTEN↑,
"highlight2" >p‑GSK‐3β↓, Level of phosphorylated glycogensynthase kinase 3ǃ (GSK3ǃ), (a serine/threonine kinase) and cyclin D1 were potentially decreased by fisetin which is in line with raised non-phosphorylated levels of GSK3ǃ
"highlight2" >GSK‐3β↑,
"highlight2" >NF-kB↓, Down-regualtion of NF-κB along with significant up-regulations in IκB upon fisetin treatment correlates with the down-regulation of p-Akt levels.
"highlight2" >IKKα↑,
"highlight2" >Cyt‑c↑, activates the efflux of cytochrome C

3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
"highlight2" >ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
"highlight2" >TumCCA↓, inhibition of the cell cycle;
"highlight2" >HSPs↓, inhibition of heat shock proteins;
"highlight2" >RAS↓, inhibition of Ras protein expression.
"highlight2" >ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
"highlight2" >Ca+2↑,
"highlight2" >MMP↓,
"highlight2" >Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
"highlight2" >Endon↑,
"highlight2" >MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
"highlight2" >MMP2↓,
"highlight2" >MMP7↓,
"highlight2" >MMP-10↓,
"highlight2" >VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
"highlight2" >NF-kB↓,
"highlight2" >p65↓,
"highlight2" >iNOS↓,
"highlight2" >COX2↓,
"highlight2" >uPA↓,
"highlight2" >PI3K↓,
"highlight2" >FAK↓,
"highlight2" >MEK↓,
"highlight2" >ERK↓,
"highlight2" >JNK↓,
"highlight2" >p38↓,
"highlight2" >cJun↓,
"highlight2" >FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 38

Results for Effect on Cancer/Diseased Cells:
ACC↑,3,   AIF↑,2,   Akt↓,13,   p‑Akt↓,2,   p‑Akt↑,1,   AMPK↑,5,   angioG↓,6,   antiOx↓,1,   AP-1↓,2,   Apoptosis↓,1,   Apoptosis↑,8,   AR↓,1,   ATF4↓,1,   ATF4↑,6,   ATF6↑,1,   ATG5↑,1,   ATM↑,1,   BAD↑,4,   Bak↑,1,   BAX↑,8,   BBB↑,1,   Bcl-2↓,9,   Bcl-xL↓,2,   Beclin-1↑,1,   BID↑,1,   BIM↑,4,   BioAv↓,4,   BioAv↑,3,   BioAv↝,1,   Ca+2↑,6,   cardioP↑,1,   Casp↑,5,   Casp3↑,13,   cl‑Casp3↑,3,   Casp7↑,2,   Casp8↑,7,   cl‑Casp8↑,2,   Casp9↑,8,   cl‑Casp9↑,3,   CD133↓,2,   CD44↓,2,   CDC2↓,3,   CDC25↓,4,   CDK1↓,1,   CDK2↓,12,   CDK4↓,10,   CDK6↓,4,   cFos↓,5,   chemoP↑,2,   ChemoSen↑,10,   CHK1↑,1,   Chk2↑,1,   CHOP↑,5,   cJun↓,6,   p‑cJun↑,1,   cMyc↓,1,   cognitive↑,1,   COX2↓,11,   cycA1↓,2,   cycD1↓,9,   cycE↓,6,   Cyt‑c↑,13,   Diablo↑,5,   DNAdam↑,8,   Dose↑,1,   Dose↝,1,   DR4↑,1,   DR5↑,6,   E-cadherin↓,1,   E-cadherin↑,5,   eff↓,3,   eff↑,10,   eff∅,1,   EGF↓,2,   EGFR↓,11,   p‑eIF2α↑,1,   EMT↓,8,   Endon↑,1,   p‑ENO1↓,1,   eNOS↓,1,   ER Stress↑,9,   ERK↓,7,   ERK↑,1,   p‑ERK↓,1,   FAK↓,2,   Fas↑,3,   Fibronectin↓,2,   FOXO3↑,1,   GRP78/BiP↑,4,   GSK‐3β↑,2,   p‑GSK‐3β↓,1,   GSTs↓,2,   GSTs↑,1,   GSTs↝,1,   p‑H3↓,1,   Half-Life↓,1,   Half-Life↝,2,   hepatoP↑,1,   HER2/EBBR2↓,3,   Hif1a↓,1,   HO-1↑,5,   HSF1↓,1,   HSP27↓,2,   HSP27↝,1,   HSP70/HSPA5↓,3,   HSP70/HSPA5↝,1,   HSPs↓,1,   IAP1↓,1,   IAP2↓,2,   IGF-1↓,1,   IKKα↑,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,3,   iNOS↓,2,   IRE1↑,3,   JAK1↓,2,   JNK↓,1,   JNK↑,2,   p‑JNK↑,1,   Keap1↓,1,   Ki-67↓,1,   LC3s↑,1,   LDH↑,1,   lipid-P↓,1,   MAPK↓,4,   MAPK↑,1,   Mcl-1↓,6,   MDM2↓,1,   MEK↓,2,   memory↑,1,   MET↓,1,   MMP↓,16,   MMP-10↓,1,   MMP1↓,3,   MMP13↓,1,   MMP2↓,12,   MMP3↓,2,   MMP7↓,6,   MMP9↓,13,   MMPs↓,1,   mtDam↑,1,   mTOR↓,10,   mTOR↑,1,   p‑mTOR↓,1,   mTORC1↓,6,   mTORC2↓,3,   mTORC2↑,1,   Myc↓,1,   N-cadherin↓,4,   neuroP↑,2,   NF-kB↓,18,   NF-kB↑,1,   NO↓,1,   NO↑,1,   NOX↑,1,   NRF2↓,3,   NRF2↑,7,   other↝,1,   P-gp↓,1,   P21↑,7,   p27↑,2,   p38↓,4,   p38↑,1,   p‑p38↓,1,   p‑p38↑,1,   P450↓,1,   P450↝,1,   P53?,1,   P53↑,10,   p65↓,2,   p70S6↓,1,   cl‑PARP↑,12,   PCK1↓,1,   PCNA↓,2,   PERK↑,2,   PGE2↓,6,   PI3K↓,11,   PI3K↑,1,   PKCδ↓,3,   PTEN↑,3,   RadioS↑,5,   RAS↓,2,   p‑RB1↓,1,   RenoP↑,2,   Rho↓,1,   Risk↓,1,   ROCK1↑,1,   ROS↓,8,   ROS↑,21,   ROS∅,1,   mt-ROS↑,2,   Securin↓,1,   selectivity↑,6,   Snail↓,2,   STAT3↓,3,   survivin↓,4,   TCF↑,1,   TCF-4↓,2,   TET1↓,1,   TGF-β↓,1,   TNF-α↓,2,   TOP1↓,1,   TOP2↓,1,   TRAIL↑,2,   TRAILR↑,1,   TSC2↑,1,   TumCA↓,1,   TumCCA↓,1,   TumCCA↑,14,   TumCD↑,1,   TumCG↓,5,   TumCI↓,6,   TumCMig↓,6,   TumCP↓,5,   tumCV↓,6,   TumMeta↓,2,   Twist↓,2,   uPA↓,11,   UPR↑,1,   VEGF↓,7,   VEGFR2↓,1,   Vim↓,5,   Wnt↓,10,   XBP-1↑,1,   XIAP↓,1,   Zeb1↓,1,   ZO-1↑,1,   β-catenin/ZEB1↓,6,  
Total Targets: 229

Results for Effect on Normal Cells:
12LOX↓,1,   antiOx↓,1,   antiOx↑,5,   Aβ↓,1,   BBB↑,1,   BDNF↑,1,   BG↓,1,   cardioP↑,1,   Casp↓,1,   Catalase↑,2,   p‑cMyc↑,1,   COX2↓,1,   DNAdam↓,1,   Dose↑,1,   eff↑,1,   ERK↑,1,   GPx↑,1,   GSH↑,2,   GSTs↑,1,   HO-1↑,1,   IL1β↓,2,   IL6↓,1,   IL6↑,1,   Inflam↓,7,   Insulin↑,1,   lipid-P↓,1,   neuroP↑,4,   NF-kB↓,1,   NO↓,1,   NO↑,1,   NRF2↑,2,   p16↓,1,   P21↓,1,   P53↓,1,   PKCδ↑,1,   PTEN↑,1,   ROS↓,5,   SOD↑,2,   TNF-α↓,2,   toxicity↑,1,  
Total Targets: 40

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:78  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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