condition found tbRes List
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


TOP1, Topoisomerase I: Click to Expand ⟱
Source:
Type:
Topoisomerase I (TOP1) is an essential nuclear enzyme involved in relieving DNA supercoiling during replication and transcription.
• Elevated TOP1 expression has been observed in several tumor types, such as colorectal, ovarian, breast, and lung cancers.
• Increased TOP1 levels may correlate with higher proliferation rates, as actively dividing tumor cells require efficient relief of DNA.

• In some cancers, high TOP1 expression has been associated with aggressive tumor behavior, higher grade, and potentially poorer clinical outcomes. This may be due in part to increased proliferation and/or a greater propensity for genomic instability.
• In other contexts, TOP1 expression might indicate sensitivity to TOP1-targeted therapies. For example, tumors with high TOP1 activity may respond better to chemotherapeutic agents (e.g., irinotecan) that target the enzyme, potentially improving outcomes when appropriate treatment is administered.

TOP1 is a critical enzyme in maintaining DNA integrity whose expression in cancers can reflect tumor proliferation and genomic instability. While high TOP1 expression is often associated with aggressive tumor behavior and poorer prognosis in several cancer types, it also has therapeutic relevance because tumors with elevated TOP1 may be more sensitive to TOP1 inhibitors.
Scientific Papers found: Click to Expand⟱
2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
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)
Diablo↑,
Casp↑,
cl‑PARP↑,
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.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
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
P21↑,
p27↑,
cycD1↓,
cycE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
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.
Vim↓,
EMT↓,
Twist↓,
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
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
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
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   Akt↓,1,   AMPK↑,1,   AP-1↓,1,   ATF4↑,1,   Bak↑,1,   Bcl-2↓,1,   Bcl-xL↓,1,   BID↑,1,   BIM↑,1,   Casp↑,1,   Casp3↑,1,   Casp9↑,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   cFos↓,1,   cJun↓,1,   COX2↓,1,   cycD1↓,1,   cycE↓,1,   Cyt‑c↑,1,   Diablo↑,1,   DNAdam↑,1,   E-cadherin↑,1,   EMT↓,1,   ER Stress↑,1,   GRP78/BiP↑,1,   HSF1↓,1,   IRE1↑,1,   MAPK↓,1,   Mcl-1↓,1,   MMP↓,1,   MMP2↓,1,   MMP7↓,1,   MMP9↓,1,   mtDam↑,1,   mTOR↓,1,   NF-kB↓,1,   P21↑,1,   p27↑,1,   P53↑,1,   cl‑PARP↑,1,   PGE2↓,1,   RadioS↑,1,   ROS↓,1,   ROS↑,1,   TCF-4↓,1,   TOP1↓,1,   TOP2↓,1,   TumCCA↑,1,   TumMeta↓,1,   Twist↓,1,   uPA↓,1,   Vim↓,1,   Wnt↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 57

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: TOP1, Topoisomerase I
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:78  Target#:1117  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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