P450 Cancer Research Results

P450, cytochrome P450 (CYP) family: Click to Expand ⟱
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The cytochrome P450 (CYP) family includes many isoenzymes that play key roles in metabolizing endogenous substances (like hormones) and xenobiotics (including drugs and toxins). Changes in the expression of these enzymes in various cancers can affect carcinogen activation, drug metabolism, and overall tumor biology, influencing both cancer risk and prognosis.

CYP1B1
– Frequently overexpressed in several cancers including breast, ovarian, prostate, and colorectal cancers.
– Its expression is often low in normal tissues, making it a potential target for selective cancer therapies.

2. CYP3A4 and CYP3A5
These enzymes are highly expressed in the liver, but their expression is also observed in extrahepatic tissues.
– In cancer, CYP3A enzymes can be variably expressed; for instance, CYP3A4 may be upregulated in some liver cancers but downregulated in others.

3. CYP2E1
– CYP2E1 is expressed in the liver and extrahepatic tissues.
– Elevated CYP2E1 activity can lead to increased production of reactive oxygen species (ROS), contributing to DNA damage and cancer progression.

4. CYP19A1 (Aromatase)
– Aromatase converts androgens to estrogens and is expressed in adipose tissue as well as in certain tumors such as breast cancer.
– Its local expression in breast tumors can increase estrogen levels, promoting hormone-dependent tumor growth.

5. CYP2C Family (e.g., CYP2C8, CYP2C9, CYP2C19)
– These enzymes are involved in metabolizing various drugs and are expressed in the liver and intestines.
– Their expression levels can be altered in different tumor types, potentially affecting drug metabolism.

CYP450 enzymes are a large family with diverse roles in cancer biology.
• Their expression in cancers (e.g., CYP1B1, CYP3A4/5, CYP2E1, CYP19A1) has been linked to both the development and progression of tumors, as well as influencing responses to therapy.
Scientific Papers found: Click to Expand⟱
2852- FIS,    A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms
- Review, CRC, NA
Risk↓, Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC)
P53↑, increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction
MDM2↓,
COX2/PTGS2↓, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways
Wnt↓,
NF-kB↓,
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
CDK4↓,
p‑RB1↓,
cycE/CCNE↓,
P21↑,
NRF2↓, Pandey and Trigun revealed that fisetin induces apoptosis in CRC cells by inhibiting autophagy and suppressing Nrf2
ROS↑, Furthermore, fisetin elevated ROS levels and downregulated Nrf2 expression, indicating Nrf2 suppression in fisetin-induced apoptosis in CRC cells.
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
Fas↑,
TRAIL↑,
DR5↑,
MMP↓, Fisetin also caused mitochondrial membrane depolarization, leading to the release of Smac/DIABLO and cytochrome c
Cyt‑c↑,
selectivity↑, enhanced cellular uptake, and induction of apoptosis in cancer cells
P450↝, Fisetin also affected the activities of cytochrome P450 (CYP450 3A4) and glutathione-S-transferase
GSTs↝,
RadioS↑, fisetin pretreatment heightened the radiosensitivity of p53-mutant HT29 human CRC cells
Inflam↓, Fisetin suppresses inflammation in the colon and CRC
β-catenin/ZEB1↓, fisetin in treating colon cancer, revealing its capability to effectively downregulate β-catenin and COX-2
EGFR↓, fisetin decreased EGFR and NF-κB activation in HT29 cells
TumCCA↑, It induces cell cycle arrest, disrupting the transition from the G1 to the S phase, as well as causing G2/M phase arrest
ChemoSen↑, intervention with fisetin and 5-FU appeared to extend the lifespan of the experimental animals

7606- I3C,    Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol
- Human, Nor, NA
P450↝, Indole-3-carbinol (I3C), obtained from cruciferous vegetables (e.g., cabbage, broccoli, etc.), is a known inducer of oxidative P-450 metabolism in animals.
2/16-OHE1↑, estradiol 2-hydroxylation before and after exposure to I3C. In a group of 12 healthy volunteers, the average extent of reaction increased by approximately 50% during this short exposure

8080- KAE,    Hepatoprotective Effect of Kaempferol—A Review
- Review, Nor, NA
*hepatoP↑, Kaempferol, a naturally occurring flavonoid, has demonstrated significant hepatoprotective effects in preclinical models
*SIRT1↑, This substance activates the SIRT1/AMPK signalling pathway, improves mitochondrial function, inhibits proinflammatory cytokine production via TLR4/NF-κB suppression and attenuates hepatic stellate cell activation by modulating the TGF-β/Smad pathwa
*AMPK↑,
*TLR4↓,
*NF-kB↓,
*GutMicro↑, kaempferol regulates the composition of the gut microbiota, thus improving bile acid metabolism and alleviating steatosis and fibrosis.
*Dose↝, The most significant amounts of kaempferol can be found in vegetables such as kale, spinach, onions, or beverages, especially black or green tea infusions
*BioAv↓, the bioavailability of the various chemical forms of oral kaempferol is low and has been calculated to be around 2%
*BioAv↑, However, there are some modern approaches (nanoparticles, structural modifications, chimeric molecules) that could certainly be exploited to improve kaempferol bioavailability [
*CYP2E1↓, including SIRT1 activation, CYP2E1 inhibition, TLR4/NF-κB suppression and ALK5/Smad pathway interference
*lipidLev↓, Reduction of Hepatic Lipid Accumulation
*COX2/PTGS2↓, Kaempferol can also suppress the production and expression of COX-2, IL-1β, TNF-α, and IL-6 mRNA, which play key roles in inflammation
*IL1β↓,
*TNF-α↓,
*IL6↓,
*NO↓, reduces the levels of NO and PGE2 while lowering iNOS mRNA expression in cases of acute liver injury.
*PGE2↓,
*iNOS↓,
*SOD↑, increased SOD activity and decreased MDA levels in the liver were observed when compared with the haemorrhagic shock group.
*MDA↓,
*ROS↓, inhibit CYP2E1 at both the expression and activity levels, consequently leading to a reduction in ROS levels and liver damage.
*AST↓, The significant decrease in serum AST and ALT levels is due to this inhibitory effect.
*ALAT↓,
*GSH↑, The induction of reactive antioxidant enzymes (GSH and SOD) by this compound
*SOD↑,
*Cyt‑c↓, inhibiting hepatocyte apoptosis through the reduction of apoptosis-related proteins, including cytochrome c, Bax, Bcl-2, caspases:3, 8 and 9
*BAX↓,
*Casp3↓,
*Casp8↓,
*Casp9↓,
*COL1↓, Kaempferol has been shown to be capable of inhibiting type I collagen expression in HSCs and reducing collagen density in liver tissue
*p‑SMAD2↓, reducing the phosphorylation of Smad2 and Smad3 by the serine/threonine kinase, attenuating α-SMA production, and inhibiting TGF-β-stimulated HSCs
*p‑SMAD3↑,
*α-SMA↓,
*TGF-β↓,
*P450↝, Kaempferol interacts with cytochrome P450 enzymes, including CYP3A4, which is key to drug metabolism.
*P-gp/ABCB1↓, It has been demonstrated that kaempferol is capable of inhibiting P-gp, which may consequently result in an enhancement of the bioavailability of drugs that are P-gp substrates.
*BioEnh↑,


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

2/16-OHE1↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

GSTs↝, 1,   NRF2↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,  

Cell Death(tgid=5) ⓘ

Casp8↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   MDM2↓, 1,   TRAIL↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycE/CCNE↓, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 1,  

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

Wnt↓, 1,  

Migration(tgid=13) ⓘ

β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   P450↝, 2,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,  

Functional Outcomes(tgid=23) ⓘ

Risk↓, 1,  
Total Targets: 30

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

CYP2E1↓, 1,   GSH↑, 1,   MDA↓, 1,   ROS↓, 1,   SOD↑, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   AMPK↑, 1,   lipidLev↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

BAX↓, 1,   Casp3↓, 1,   Casp8↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   iNOS↓, 1,  

Migration(tgid=13) ⓘ

COL1↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↑, 1,   TGF-β↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL1β↓, 1,   IL6↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioEnh↑, 1,   Dose↝, 1,   P450↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

hepatoP↑, 1,  
Total Targets: 39

Scientific Paper Hit Count for: P450, cytochrome P450 (CYP) family
1 Fisetin
1 Indole-3-carbinol
1 Kaempferol
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

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