CYP3A4 Cancer Research Results
CYP3A4, CYP3A4: Click to Expand ⟱
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CYP3A4 is the most abundant cytochrome P450 enzyme in the liver and is also expressed in extrahepatic tissues.
– It metabolizes a wide range of drugs and endogenous substrates, including hormones.
– In some studies, higher CYP3A4 expression has been correlated with poorer response to treatment and potentially worse survival.
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Scientific Papers found: Click to Expand⟱
*BioAv↓, We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range cu
Half-Life∅, elimination half-life (T1/2) averaging 2.52 ± 0.56h
*BioAv↓, bioavailability is in the region of 30%
Dose∅, Blood and urine samples were taken following a meal consisting of 2g parsley/kg body weight–which was equivalent to ∼17mg of apigenin -> 28–337nmol/L at 6–10h after consumption
eff↑, Apigenin and quercetin enhance their own and each other’s bioavailability by downregulating the activity of ABC transporters
CYP1A2↓, status of apigenin as an inhibitor of CYP1A2, CYP2C9 and CYP3A4
CYP2C9↓,
CYP3A4↓,
CYP3A4↓, Bufalin showed a modest but significant inhibition of CYP3A4 both in vitro and in vivo.
Apoptosis↑, Bufalin has been shown to induce apoptosis in human leukemia HL-60 cells and human tumor cells12, 13, 14, 15, 16, 17, 18.
AntiTum↑, In conclusion, the present study demonstrates that bufalin, which has been reported to exhibit significant anti-tumor activity12, 13, 14, 15, 16, 17, 18,
Dose↝, Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localised or locally advanced) nonmetastatic prostate cancer.
BioAv↑, Bicalutamide is slowly and saturably absorbed, but absorption is unaffected by food.
Half-Life↑, It has a long plasma elimination half-life (1 week) and accumulates about 10-fold in plasma during daily administration.
CYP3A4↓, In vitro data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a lesser extent, CYP2C9, 2C19 and 2D6.
PSA↓, Bicalutamide produces a dose-related decrease in prostate-specific antigen (PSA) at dosages < or = 150 mg/day.
P450↓, Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents
CYP3A4↓, B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%).
CYP2C9↓,
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*eff↑, L-borneol has better potential in cerebrovascular diseases.
*eff↑, D-borneol exhibits better antitumour sensitizing effects than L-borneol.
*toxicity↝, Synthetic borneol is less safe. Synthetic borneol is widely used because of its advantages of low cost and easy availability.
*Inflam↓, It has anti-inflammatory, analgesic, antipyretic, antibacterial, neuroprotective, and permeation-promoting effects.
*Bacteria↓,
*neuroP↑,
*Half-Life↝, oral administration. It reaches its highest concentration in 30 min, and its half-life is 18 h
*BBB↑, and can easily pass through the BBB and blood–ocular barrier (BOB).
*BioEnh↑, Borneol can promote the absorption and affect the distribution of other drugs, which is beneficial for reducing the dosage, prolonging the action time, and improving the curative effects of these drugs
*P-gp/ABCB1↓, inhibitory activity against P-gp is as follows: L-borneol > D-borneol ≈ synthetic borneol.
*CYP3A4↓, inhibition of intestinal CYP3A4 would improve the bioavailability of drugs.
*ROS↓, and reduce the rate of cerebral oedema and the volume of infarcts by inhibiting oxidative stress
*neuroP↑, neuroprotective effects of the three kinds of borneol are as follows: L-borneol > synthetic borneol > D-borneol
*CYP3A4↓, bergamottin—a substance thought to be able to irreversibly inhibit CYP 3A4 activity—in the juice.
AntiCan↑, This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity
toxicity↓, Due to its safety and efficacy, GBLs have become one of the most widely used herbs in Europe and the United States, with annual sales of related products reaching billions of dollars
ChemoSen↑, ginkgetin synergizes with chemotherapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects.
chemoP↑, In addition to standalone use, ginkgetin has synergistic effects with other drugs by enhancing drug efficacy and alleviating side effects.
TumCCA↑, mechanisms, including inducing cell cycle arrest, triggering programmed cell death, and preventing invasion and angiogenesis.
TumCD↑,
TumCI↓,
angioG↓,
Ferroptosis↑, figure 1
Imm↑, emerging evidence suggests that ginkgetin could enhance the body’s immunity and has an anti-tumor function
MOMP↑, ginkgetin triggered the intrinsic apoptosis pathway, demonstrated by increased mitochondrial outer membrane permeabilization (MOMP) and the release of Cytochrome c into the cytoplasm,
Cyt‑c↑,
Casp↑, which activated the caspase cascade and upregulated cleaved caspase-3, caspase-9, and PARP, ultimately leading to apoptosis [
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Apoptosis↑,
ROS↑, Moreover, ginkgetin mediated the activation of caspase cascade by the intracellular reactive oxygen species generated possibly through auto-oxidation of this biflavone, leading to apoptosis in OVCAR-3 cells
TumAuto↑, Ginkgetin induced autophagic cell death in non-small cell lung cancer (NSCLC) A549 cells
GPx4↓, Ginkgetin synergized with cisplatin to increase ferroptosis in NSCLC cells, which was confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio
xCT/SLC7A11↓,
RadioS↑, Similarly, when breast cancer cells generated radioresistance, ginkgetin promoted ferroptosis in 4T1 cells after radiotherapy by suppressing the Nrf2/HO-1 axis activity, elevating intracellular levels of reactive oxygen species (ROS) and ferrous ions
NRF2↓,
HO-1↓,
HSP90↓, MD simulations showed minimal fluctuations in the binding mode between ginkgetin and Hsp90, suggesting that ginkgetin may be an effective Hsp90 inhibitor
Dose↝, The IC50 values of ginkgetin treatment ranged from 0.58 to 150 μM, which varied due to differences in cell type, treatment time, number of plated cells, and treatment method.
Dose↝, For animal experiments, the concentration of administration ranged from 10 to 100 mg/kg, owing to different types of tumors and administration methods.
BioAv↓, Consequently, improving the bioavailability and water solubility of ginkgetin is an urgent issue that needs to be addressed
BioAv↝, In addition to considering administration routes such as intraperitoneal or intravenous injection, improvements can be made through innovative dosage form design and advanced drug delivery platforms
CYP3A4↓, research has shown that ginkgetin exhibited significant inhibition activity towards CYP3A4, which is a pivotal enzyme in the metabolic processing of many commonly used drugs, and the IC50 value was evaluated as 0.106 ± 0.004 μM
*toxicity↑, Moreover, ginkgetin induced acute kidney injury in treated mice and the main pathological lesions were confirmed in the tubule, glomeruli, and interstitium injuries
*toxicity↝, ginkgetin displayed potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressing hUGT1A1), which ...plays a crucial role in the metabolic detoxification of endogenous toxicants (e.g., bilirubin) and a variety of clinical drugs
*CYP2C6↓, The licorice compounds isoliquiritigenin, licoricidin, licochalcone A, 18β-glycyrrhetinic acid, and glycycoumarin inhibited one or more members of the CYP2C family of enzymes.
*CYP3A4↓, Isoliquiritigenin, glabridin and licoricidin competitively inhibited CYP3A4
*P450↓, varying potential for drug-botanical interactions as inhibitors of cytochrome P450 isoforms.
*other↑, Each species of licorice displays a unique profile of constituents with potential for drug interactions.
Risk↓, strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer.
AntiCan↑, Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects.
TumCP↓, PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis
TumMeta↓,
ChemoSen↑, combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy
*BioAv↑, ITCs are released from glucosinolates by the action of the enzyme myrosinase. The enzyme myrosinase can be activated by cutting or chewing the vegetables, but heating can destroy its activity
*other↝, Although water cress and broccoli are known to be the richest source, PEITC can also be obtained from turnips and radish
*Dose↝, In a study conducted with human volunteers, approximately 2 to 6 mg of PEITC was found to be released by the consumption of one ounce of watercress
Dose↓, significant anti-cancer effects can be achieved at micromolar concentrations of PEITC.
*BioAv↑, PEITC is highly bioavailable after oral administration. A single dose of 10–100 μmol/kg PEITC in rats resulted in bioavailability ranging between 90–114%
*Dose↝, Furthermore, about 928.5±250nM peak plasma concentration of PEITC was achieved in human subjects, after the consumption of 100g watercress.
*Half-Life↝, time to reach peak plasma concentration was observed to be 2.6h±1.1h with a t1/2 4.9±1.1h
*toxicity↝, long term studies are required to establish the safety profile of PEITC, since regular intake of PEITC can cause its accumulation resulting in cumulative effects, which could be toxic.
GSH↓, The conjugation of PEITC with intracellular glutathione and the subsequent removal of the conjugate result in depletion of glutathione and alteration in redox homeostasis leading to oxidative stress
ROS↑, PEITC-mediated generation of reactive oxygen species (ROS) is known to be a general mechanism of action leading to cytotoxic effects, especially specific to cancer cells
CYP1A1↑, PEITC on one hand causes induction of CYP1A1 and CYP1A2; however, it inhibits activity of certain CytP450 enzymes, such as CYP2E1, CYP3A4 and CYP2A3
CYP1A2↑,
P450↓,
CYP2E1↑,
CYP3A4↓,
CYP2A3/CYP2A6↓,
*ROS↓, PEITC treatment caused a significant increase in the activities of ROS detoxifying enzymes such as glutathione peroxidase1, superoxide dismutase 1 and 2. This was also confirmed in human study where subjects were administered watercress, a major sour
*GPx1↑,
*SOD1↑,
*SOD2↑,
Akt↓, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types
EGFR↓, PEITC is also known to inhibit EGFR and HER2, which are important growth factors and regulators of Akt in different cancer models
HER2/EBBR2↓,
P53↑, PEITC-mediated activation of another tumor suppressor, p53 was observed in oral squamous cell carcinoma, causing G0/G1 phase arrest in multiple myeloma,
Telomerase↓, PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells
selectivity↑, generation of reactive oxygen species (ROS), which also has been shown to be the basis of selectivity of PEITC toward cancer cells leaving normal cells undamaged [
MMP↓, ROS generation by PEITC leads to mitochondrial deregulation and modulation of proteins like Bcl2, BID, BIM and BAX, causing the release of cytochrome c into cytosol leading to apoptosis
Cyt‑c↑,
Apoptosis↑,
DR4↑, induction of death receptors and Fas-mediated apoptosis
Fas↑,
XIAP↓, PEITC-mediated suppression of anti-apoptotic proteins like XIAP and survivin, which are up-regulated in cancer cells
survivin↓,
TumAuto↑, PEITC induces autophagic cell death in cancer cells
Hif1a↓, PEITC directly or indirectly suppresses HIF1α
angioG↓, is possible that PEITC can block angiogenesis by non-hypoxic mechanisms also.
MMPs↓, Various studies with PEITC have shown suppression of invasion through inhibition of matrix metalloproteinases along with anti-metastatic effects caused by suppression of ERK kinase activity and transcriptional activity of NFkB
ERK↓,
NF-kB↓,
EMT↓, PEITC was also known to inhibit processes, such as epithelial to mesenchymal transition (EMT), cell invasion and migration, which are essential pre-requisites for metastasis
TumCI↓,
TumCMig↓,
Glycolysis↓, reduced rates of glycolysis in PEITC-treated cells and depletion of ATP lead to death in prostate cancer cells
ATP↓,
selectivity↑, PEITC (5μM) treatment suppressed glycolysis in the cancer cells, but no changes were observed in normal cells.
*antiOx↑, the antioxidant effect is achieved at very low ITC levels in normal cells as shown in various animal models
Dose↝, At higher concentrations, ITCs may generate ROS by depleting antioxidant levels. PEITC is known to cause ROS generation, which is the major mechanism of toxicity in cancer cells
other↝, There is a continuous leakage of electrons from the electron transport chain (ETC), which is major source of ROS production. PEITC causes generation of endogenous ROS by disrupting mitochondrial respiratory chain
OCR↓, PEITC also inhibits mitochondrial complex III activity and reduces the oxygen consumption rate in prostate cancer cells
GSH↓, PEITC binds to GSH and causes its depletion in cancer cells leading to ROS-induced cell damage
ITGB1↓, PEITC was found to inhibit major integrins, such as ITGB1, ITGA2 and ITGA6 in prostate cancer cells
ITGB6↓,
ChemoSen↑, Using pre-clinical studies, improved outcomes were observed when the conventional agents, such as docetaxel, metformin, vinblastine, doxorubicin and HDAC inhibitors were combined with PEITC
TumCCA↑, arresting cell cycle in the G2/M and G1 phase
CYP1A1↓, Sulforaphane inhibits CYP1A1 and CYP3A4 and decease the activity of CYP3A4
CYP3A4↓,
Cyt‑c↑, release of cytochrome C from the mitochondria
Casp9↑,
Apoptosis↑,
ROS↑, generation of reactive oxygen species (ROS), and mitogen-activated protein kinases (MAPK)
MAPK↑,
P53↑, sulforaphane treatment increased p53 protein expression with associated increase in the protein levels of Bax
BAX↑,
ChemoSen↑, Combination therapies target multiple cell survival pathways, which results in synergism
HDAC↓, HDACi Histone deacetylase inhibition
GSH↓, fig 3
HO-1↑, They found that the protective effect of sulforaphane is mediated by the activation of the Keap1/Nrf2/ARE pathway, which consequently induce HO-1
Showing Research Papers: 1 to 10 of 10
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress(tgid=1) ⓘ
CYP1A1↓, 1, CYP1A1↑, 1, CYP2E1↑, 1, Ferroptosis↑, 1, GPx4↓, 1, GSH↓, 3, HO-1↓, 1, HO-1↑, 1, NRF2↓, 1, ROS↑, 3, xCT/SLC7A11↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 1, MMP↓, 1, OCR↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
CYP3A4↓, 7, Glycolysis↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 1, Apoptosis↑, 4, BAX↑, 1, Casp↑, 1, cl‑Casp3↑, 1, Casp9↑, 1, cl‑Casp9↑, 1, Cyt‑c↑, 3, DR4↑, 1, Fas↑, 1, Ferroptosis↑, 1, MAPK↑, 1, MOMP↑, 1, survivin↓, 1, Telomerase↓, 1, TumCD↑, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
HER2/EBBR2↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other↝, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
HSP90↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
TumAuto↑, 2,
DNA Damage & Repair(tgid=10) ⓘ
P53↑, 2, cl‑PARP↑, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
TumCCA↑, 2,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
EMT↓, 1, ERK↓, 1, HDAC↓, 1,
Migration(tgid=13) ⓘ
ITGB1↓, 1, ITGB6↓, 1, MMPs↓, 1, TumCI↓, 2, TumCMig↓, 1, TumCP↓, 1, TumMeta↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 2, EGFR↓, 1, Hif1a↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
Imm↑, 1, NF-kB↓, 1, PSA↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 1, BioAv↑, 1, BioAv↝, 1, ChemoSen↑, 4, CYP1A2↓, 1, CYP1A2↑, 1, CYP2A3/CYP2A6↓, 1, CYP2C9↓, 2, Dose↓, 1, Dose↝, 4, Dose∅, 1, eff↑, 1, Half-Life↑, 1, Half-Life∅, 1, P450↓, 2, RadioS↑, 1, selectivity↑, 2,
Clinical Biomarkers(tgid=22) ⓘ
EGFR↓, 1, HER2/EBBR2↓, 1, PSA↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 2, AntiTum↑, 1, chemoP↑, 1, Risk↓, 1, toxicity↓, 1,
Total Targets: 81
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 1, GPx1↑, 1, ROS↓, 2, SOD1↑, 1, SOD2↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
CYP2C6↓, 1, CYP3A4↓, 3,
Transcription & Epigenetics(tgid=7) ⓘ
other↑, 1, other↝, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 1, P-gp/ABCB1↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
Inflam↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 2, BioAv↑, 2, BioEnh↑, 1, Dose↝, 2, eff↑, 2, Half-Life↝, 2, P450↓, 1,
Functional Outcomes(tgid=23) ⓘ
neuroP↑, 2, toxicity↑, 1, toxicity↝, 3,
Infection & Microbiome(tgid=24) ⓘ
Bacteria↓, 1,
Total Targets: 23
Scientific Paper Hit Count for: CYP3A4, CYP3A4
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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