COX1 Cancer Research Results
COX1, COX-1: Click to Expand ⟱
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COX‑1 is traditionally considered a constitutively expressed enzyme involved in “housekeeping” functions, while COX‑2 is more frequently studied in relation to cancer.
• The prognostic impact of COX‑1 may vary based on cancer subtype, stage, and interplay with other inflammatory mediators (e.g., COX‑2).
• Many studies assess combined cyclooxygenase profiles (COX‑1/COX‑2) rather than COX‑1 alone.
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Scientific Papers found: Click to Expand⟱
*COX1↓, believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes
*other?, believed that acetaminophen is metabolized to p-aminophenol, which crosses the blood-brain barrier and gets metabolized by fatty acid amide hydrolase to yield N-acylphenolamine (AM404).
*BBB↑,
TRPV1↑, by activating TRPV1 receptor, AM404 produced outward currents that were measured using whole-cell patch-clamp recordings and acted as a partial agonist in trigeminal neurons
AntiAg↑, The antithrombotic action of aspirin (acetylsalicylic acid) is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX)
COX1↓, Aspirin is an approximately 150- to 200-fold more potent inhibitor of the (constitutive) isoform of the platelet enzyme (COX-1) than the (inducible) isoform (COX-2)
eff↑, Aspirin is the "gold standard" antiplatelet agent for prevention of arterial thromboses.
TumMeta↓, The included studies demonstrated that aspirin suppresses metastatic dissemination across multiple cancer types through coordinated platelet-dependent and tumor-intrinsic mechanisms.
COX1↓, Aspirin consistently inhibited platelet aggregation and COX-1-dependent TXA2 production, disrupting platelet–tumor cell interactions, intravascular metastatic niche formation, and platelet-mediated immune suppression.
TXA2↓,
AntiAg↑, Beyond platelet effects, aspirin suppressed EMT, migration, and invasion through modulation of EMT transcriptional regulators and inflammatory signaling pathways.
EMT↓,
TumCMig↓,
TumCI↓,
AMPK↑, Additional mechanisms included activation of AMPK, inhibition of c-MYC signaling, regulation of redox-responsive pathways and impairment of anoikis resistance.
cMyc↓,
PGE2↓, Importantly, oral aspirin (20 mg/kg/day; human-equivalent ≈ 150 mg/day), administered before tumor cell injection, prevented platelet-induced metastatic enhancement and suppressed TXA2 and PGE2 production.
Dose↑, medium and high doses of aspirin reduced pulmonary metastatic burden by more than 50%, whereas low-dose aspirin was ineffective.
RadioS↑, Wang et al. [45] demonstrated that low-dose aspirin suppresses radiotherapy-induced release of immunosuppressive exosomes in breast cancer, restoring NK-cell proliferation and enhancing antitumor immunity in vivo.
PD-L1↓, Similarly, Xiao et al. [46] showed that aspirin epigenetically downregulates PD-L1 expression by inhibiting KAT5-dependent histone acetylation, thereby restoring T-cell activation
E-cadherin↑, Aspirin restored E-cadherin expression and suppressed EMT regulators, including Slug, vimentin, Twist, MMP-2, and MMP-9.
EMT↓,
Slug↓,
Vim↓,
Twist↓,
MMP2↓,
MMP9↓,
other↑, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology
Risk↓, Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use.
*toxicity↓, Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding.
other↑, In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence
*COX1↓, recent evidence highlights additional targets for aspirin in tackling cancer progression directly, irrespective of COX activity [3, 4]
TumCP↓, Such targets include energy metabolism involved in cancer proliferation, cancer associated inflammation [5] and platelet driven pro-carcinogenic activity [2].
DNArepair↑, beneficial effect of aspirin on colon cancer risk through an enhancement of DNA-repair mechanisms [2].
ChemoSen↑, ‘basic science’ basis to justify using aspirin as an adjunct to other pre-existing therapies (e.g., immunotherapy and cytotoxic chemotherapy) in the treatment of cancer progression and metastasis [2, 14].
other↓, Aspirin has been shown repeatedly to reduce thromboembolism, including in patients with cancer [15]
*cardioP↑, Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke.
*other↝, Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.
*COX1↓, irreversible acetylation of Ser530 in the enzyme prostaglandin G/H synthase-1 (commonly termed cyclooxygenase [COX]-1) and the consequent suppression of thromboxane (Tx) A2 (TxA2) formation.
*TXA2↓,
*COX1↓, Aspirin is the acetate ester of salicylic acid and acts by binding irreversibly to cyclooxygenase-1 and cyclooxygenases-2
*COX2↓,
*cardioP↑, Aspirin is consumed most often at low-doses for cardio-protection and at higher doses as an analgesic, antipyretic, and anti-inflammatory agents.
*BioAv↑, Orally ingested aspirin is absorbed rapidly and the peak concentration is reached in about 1 hour.
*BioAv↝, a rise in pH also increases the solubility of aspirin and thus the dissolution of the tablets and the presence of food delays absorption of aspirin.
*Half-Life↓, The elimination half-life of aspirin in plasma is about 20 min
Risk↓, Patients who received 100 mg daily of aspirin had reduced risks of colorectal cancer and gastric cancer and an increased risk of gastrointestinal bleeding [6].
*other↑, Low-dose of aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and pregnancy-rates in women undergoing in-vitro fertilization [19].
*AntiAg↑, antiplatelet effect of aspirin [13],
*COX2↓, The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidate
*COX1↓, The computational results confirmed that aspirin would be 10–100 times more potent against COX-1 than against COX-2,
*Inflam↓, esides its wide use in the treatment of inflammation, fever, and pain for over a century and its well-known benefit in the prevention/treatment of cardiovascular diseases,
*cardioP↑,
Risk↓, regular aspirin intake has recently been convincingly shown to reduce the overall risk of certain cancers. (1a-1e)
TumMeta↓, It has long been hypothesised that aspirin prevents cancer deaths by preventing metastasis.
TXA2↓, A recent study demonstrates this to be mediated through inhibition of Thromboxane A2 (TXA2) leading to reversal of suppression of T cell immunity.
*AntiAg↑, It was therefore hypothesised [3, 5] that aspirin prevents cancer metastasis, very likely through its anti-platelet action but the exact mechanism of action remained unclear.
COX1↓, anti-platelet activity through inhibition of cyclooxygenase-1 (COX-1) remains the main plausible mechanism.
Risk↓, dramatically reduced incidence of cancer in individuals taking daily low-dose aspirin [1–7],
*Inflam↓, Aspirin, like the vast majority of NSAIDs, is thought to exert its anti-inflammatory effects through inhibition of cyclooxygenase enzymes (COX enzymes) that regulate the production of prostaglandins.
*COX1↓,
*AntiAg↑, spirin acts to blunt a variety of pro-inflammatory responses, including the canonical inflammatory response [9–11], production of a defensive mucosal lining [12], and platelet aggregation [13, 14].
*Half-Life↓, The half-life of aspirin in the bloodstream was previously shown to be 13–19 min with a non-enzymatic hydrolysis rate of 0.023 min−1 at 37 °C in individuals given a single oral administration of aspirin.
*BioAv↑, Approximately 70% of aspirin reaches the peripheral circulation intact with maximum serum concentrations observed at 25 min after administration.
*AntiAg↑, 15R-PGs are novel products of aspirin therapy via acetylation of COX-2 and may contribute to its antiplatelet and other pharmacologic effects.
*COX1↓, Aspirin inhibits the cyclooxygenase (COX) enzymes via a unique mechanism
COX1↓, Here we show that inhibitors of cyclooxygenase 1 (COX-1), including aspirin, enhance immunity to cancer metastasis by releasing T cells from suppression by platelet-derived thromboxane A2 (TXA2).
TumMeta↓, Moreover, low-dose (75–300 mg) aspirin treatment is associated with a reduction in the rate of cancer death in individuals without metastasis at the time of cancer diagnosis
*Half-Life↓, Aspirin has a short half-life (around 20 min), such that only frequent high doses of aspirin can achieve sustained pharmacological inhibition of COX-1 and COX-2 in nucleated cells
*COX2↓, Aspirin can inhibit both COX-1 and COX-2
*TXA2↓, suppression by platelet-derived thromboxane A2 (TXA2).
Risk↓, emerging evidence suggests that aspirin may reduce the risk of certain cancers, particularly colorectal cancer (CRC).
COX1↓, Aspirin’s anticancer effects are primarily attributed to its cyclooxygenase (COX) enzyme inhibition, which decreases prostaglandin E2 (PGE2) levels and disrupts cancer-related signaling pathways.
PGE2↓,
Inflam↓, Aspirin is a versatile medication commonly used as an analgesic, anti-inflammatory, antipyretic, and antiplatelet agent [2,3].
*AntiAg↓,
PI3K↓, By irreversibly inhibiting COX-2, aspirin reduces PGE2 levels, thereby decreasing the activation of cancer-related signaling pathways such as PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) and ERK and promoting apoptosis in cancer cells
Akt↓,
Risk↓, For pancreatic cancer, aspirin for at least five years significantly reduces the risk of death, though this protective effect becomes apparent only after a five-year lag period [39].
TumMeta↓, regular aspirin use was associated with a reduced risk of cancer metastasis
COX1↓,
CTC↓,
*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)
*AntiAg↑, CAFA dose-dependently inhibited collagen-induced platelet aggregation and suppressed the production of TXA2, an aggregation-inducing autacoid associated with the strong inhibition of COX-1 in platelet microsomes exhibiting cytochrome C reductase acti
*TXA2↓, prevention of platelet aggregation-mediated thrombotic diseases.
*COX1↓,
*antiOx↑, CAPE possesses antimicrobial, antioxidant, anti-inflammatory, and cytotoxic properties.
*Inflam↓,
ChemoSen↑, CAPE is a versatile therapeutically active polyphenol and an effective adjuvant of chemotherapy for enhancing therapeutic efficacy and diminishing chemotherapy-induced toxicities.
chemoP↑, diminishing chemotherapy-induced toxicities.
COX1↓, inhibits the COX-1 and COX-2 activity
COX2↓,
selectivity↑, It has been reported that CAPE render antitumor features [43] devoid of causing cytotoxicity to normal cells [44].
NF-kB↓, CAPE inhibits the NF-κB factor
RadioS↑, ionizing radiation, the increased death of CAPE treated cells has been reported
*ROS↓, The evidences show that CAPE is potent antioxidant which can scavenge ROS and protect the cell membrane against lipid peroxidation
*lipid-P↓,
*NF-kB↓, inhibition of the activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
NF-kB↓, CAPE has been shown to block NF-κB activation in tumor
P53↑, CAPE enhances the expression of the tumor suppressor protein p53 in glioma cells
FOXO↑, CAPE also interferes with FOXO signaling by increasing the levels of the FOXO-1 downstream tumor suppressor in prostate cancer cells
Wnt↓, CAPE suppressed canonical Wnt signaling of prostate cancer cells, reducing their invasiveness
TumCI↓,
*HO-1↑, CAPE exerts its antioxidant effects through increased HO1 expression, mediated by Nrf-2
MMP9↓, CAPE has been shown to selectively inhibit human matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2)
MMP2↓,
COX1↓, CAPE has been shown to inhibit the in vitro activity of the cyclooxygenases COX-1 and COX-2
COX2↓,
5LO↓, CAPE has also been shown to inhibit arachidonate 5-lipoxygenase (5-LOX)
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*other↝, The most abundant and promising bioactive compound derived from the root of this plant is celastrol, also called tripterine, which possess a broad range of biological activities
*other↝, TW is generally used in the treatment of Crohn’s disease (CD) in China.
*CRP↓, Inflammatory parameters, including c-reactive protein (CRP), also decreased
*eff↝, Etanercept plus TW had an equivalent therapeutic effect to that of Etanercept plus MTX and were both well tolerated
*other↑, TW in human kidney transplantation (26). Rejection occurred in 4.1% of patients treated with TW versus 24.5% of control patients, showing efficacy in the prevention of renal allograph rejection
*CXCR4↓, celastrol decreases hypoxia-induced FLS invasion by inhibiting HIF-1α-mediated CXCR4 transcription
*IL1β↓, Authors have shown that it decreases the production of IL-1β, IL-6, IL-17, IL-18, and TNF by SIC cells harvested from arthritic rats
*IL6↓,
*IL17↓,
*IL18↓,
*TNF-α↓,
*MMP9↓, celastrol reduces MMP-9 production, which limits bone damage
*PGE2↓, celastrol suppresses LPS-induced expression of PEG2 via the downregulation of COX-1 and COX-2 activation
*COX1↓,
*COX2↓,
*PI3K↓, associated with a decrease in PI3K/Akt pathway
*Akt↓,
*other↑, Remarkably, this bone-protective property of celastrol in arthritic models is further supported by studies performed in cancer models
TumCCA↑, celastrol induces cell cycle arrest, apoptosis, and autophagy by the activation of reactive oxygen species (ROS)/c-Jun N-terminal kinases (JNK) signaling pathway
Apoptosis↑,
ROS↑,
JNK↑,
TumAuto↑, celastrol is still able to induce autophagy through HIF/BNIP3 activation
Hif1a↓, The inhibitory effect of celastrol on angiogenesis is mediated by the suppression of HIF-1α,
BNIP3↝,
HSP90↓, The inhibition of HSP90 by celastrol
Fas↑, activation of Fas/Fas ligand pathway in non-small-cell lung cancer
FasL↑,
ETC↓, inhibition of mitochondrial respiratory chain (MRC) complex I
VEGF↓, This inhibition of HIF-1α leads to the decrease of its target genes, such as the VEGF
angioG↓, Angiogenesis Inhibition
RadioS↑, celastrol can overcome tumor resistance to radiotherapy in prostate (129) and lung cancer cells
*neuroP↑, celastrol is a promising neuroprotective agent in animal models of neurodegenerative diseases, such as Parkinson disease (149), Huntington disease (149–151), Alzheimer disease
*HSP70/HSPA5↑, his induction of HSP70 by celastrol explains its beneficial effects not only in neurodegenerative disorders but also in inflammatory diseases.
*ROS↓, celastrol protects human dopaminergic cells from injury and apoptosis and prevents ROS generation and mitochondrial membrane potential loss
*MMP↑,
*Cyt‑c↓, It inhibits cytochrome c release, Bax/Bcl-2 alterations, caspase-9/3 activation, and p38 MAPK activation
*Casp3↓,
*Casp9↓,
*MAPK↓,
*Dose⇅, Authors discuss that it seems to have a narrow therapeutic window, and suggest that it may have a biphasic effect with protective properties at low concentrations and toxic effects at higher concentrations.
*HSPs↑, induces a set of HSPs (HSP27, 32, and 70) in rat cerebral cortical cultures, which are selectively impacted during the progression of this disease
BioAv↓, Due to this poor water solubility, celastrol has low bioavailability. oral administration of celastrol in rats results in ineffective absorption into the systemic circulation, with an absolute bioavailability of 17.06%
Dose↝, narrow therapeutic window of dose together with the occurrence of adverse effects. Our own data showed in vivo that the doses of 2.5 and 5 μg/g/day are effective and non-toxic in the treatment of arthritis in rats;
*AntiAg↑, Several studies have proved the beneficial role of curcumin on platelets . in-vivo study exhibited that curcumin inhibited platelet aggregation in monkeys
*antiOx↑, Curcumin exhibits promising antioxidant activity
*Inflam↓,
*12LOX↑, increased the production of 12-LOX
COX1↓, Curcuminoids have been demonstrated to inhibit cyclo-oxygenase and 12-lipoxygenase activities in human platelets, thus showing antioxidant activity
COX2↓, Its effectiveness in cancer is mediated by inhibition of COX-2, MMP-9, and NF-kB
MMP9↓,
NF-kB↓,
STAT3↓, EA inhibits STAT3 signaling
TumCP↓, EA inhibits cell proliferation, induces apoptosis
Apoptosis↑,
NF-kB↓, inhibiting nuclear factor-kappa B
EMT↓, suppressing epithelial–mesenchymal transition
RadioS↑, In liver cancer, EA exhibits radio-sensitizing effects
antiOx↑, As a potential antioxidant agent,
COX1↓, EA suppresses the expression of several factors, including COX1, COX2, c-myc, snail, and twist1
COX2↓,
cMyc↓,
Snail↓,
Twist↓,
MMP2↓, significantly decreased MMP-2 and MMP-9 expression and activity.
P90RSK↓,
CDK8↓, downregulate CDK8 expression and activity
PI3K↓, inactivating PI3K/Akt signaling
Akt↓,
TumCCA↑, promote cell cycle arrest
Casp8↑, ctivating caspase-8, and lowering proliferating cell nuclear antigen (PCNA) expression,
PCNA↓,
TGF-β↓,
Shh↓, suppression of the Akt, Shh, and Notch pathways, EA can prevent the growth, angiogenesis, and metastasis of pancreatic cancer
NOTCH↓,
IL6↓,
ALAT↓, decreasing liver injury biomarkers such as alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST)
ALP↓,
AST↓,
VEGF↓,
P21↑,
*toxicity∅, no toxicity was found for a 50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day
*Inflam↓, ncluding anti-inflammatory [10], anti-oxidant [11], anti-allergic [12], and anti-mutagenic [13] properties, as well as potential health advantages like gastroprotective [14], cardioprotective [15], neuroprotective [16, 17], and hepatoprotective [18,
*cardioP↑,
*neuroP↑,
*hepatoP↑,
ROS↑, Exposure to EAs induced apoptosis, accelerated cell cycle arrest, and elevated the generation of reactive oxygen intermediates [59].
*NRF2↓, As a potential antioxidant agent, it scavenges reactive oxygen species (ROS), and by upregulating of Nrf2,
*GSH↑, Moreover, EA increases reduced glutathione (GSH), which is critical for cellular defense against oxidative stress and liver damage,
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage
cardioP↑, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models
ROS↑,
AntiAg↑, EGCG can inhibit platelet aggregation induced by U46619, collagen, arachidonic acid, and toxic carotenoids and shear force-induced platelet adhesion dose-dependently by suppressing PLCγ2 and tyrosine phosphorylation
eff↑, What’s more, its combination with common antiplatelet therapeutic agents, aspirin (ASA), clopidogrel (CPD), and tiglitazarol (TCG), did not further inhibit platelet aggregation resulting in bleeding complications
COX1↓, EGCG inhibits platelet activation by inhibiting microsomal cyclooxygenase-1 activity in platelets
*SOD↑, increase in antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase, peroxiredoxin, and heme oxygenase-1
*GPx↑,
*Catalase↑,
*Prx↑,
*HO-1↑,
*Inflam↓, anti-inflammatory properties of propolis may be based on the following mechanisms:
*TNF-α↓, (1) suppression of the release of inflammatory cytokines, such as TNF-α and IL-1β;
*IL1β↓,
*IL4↑, (2) increase in production of anti-inflammatory cytokines such as IL-4 and IL-10;
*IL10↑,
*TLR4↓, (3) prevention of TLR4 activation;
*LOX1↓, (4) suppression of LOX, COX-1 and COX-2 gene expression
*COX1↓,
*COX2↓,
*NF-kB↓, (5) suppression of NF-κB and AP-1 activities;
*AP-1↓,
*ROS↓, CAPE treatment reduced ROS levels in the airway microenvironmen
*GSH↑, GSH level increased after CAPE treatment in an animal allergic asthma model
*TGF-β↓, significantly limiting secretion of eotaxin-1, TGF-β1, TNF-α, IL-4, IL-13, monocyte chemoattractant protein-1, IL-8, matrix metalloproteinase-9, and alpha-smooth muscle actin expression
*IL8↓,
*MMP9↓,
*α-SMA↓,
*MDA↓, (MDA) production and protein carbonyl (PC) levels significantly decreased
*IL6↓, Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 μg/ml.
*MMP13↓,
*PGE2↓, In particular, the production of PGE2 was significantly inhibited even at 10 μg/ml of piperine.
*AP-1↓, Piperine inhibited the migration of activator protein 1 (AP-1)
*Inflam↓, piperine significantly reduced the inflammatory area in the ankle joints
*5LO↓, piper species have shown in vitro inhibitory activity against the enzymes responsible for leukotriene and prostaglandin biosynthesis, 5-lipoxygenase and COX-1, respectively
*COX1↓,
*COX2↓, Piperine also inhibited both the protein and mRNA expression levels of IL6 and COX-2.
*ERK↓, suggested that piperine inhibition of the ERK1/2 signaling pathway blocked the migration of AP-1 into the nucleus.
*BioEnh↑, Piperine is also known to enhance the bioavailability of some drugs by inhibiting drug metabolism or by increasing absorption
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*antiOx↑, Black pepper (Piper Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential and gastro-protective modules
*ROS↓, The free-radical scavenging activity of black pepper and its active ingredients might be helpful in chemoprevention and controlling progression of tumor growth.
*chemoP↑,
TumCG↓,
*cognitive↑, piperine assist in cognitive brain functioning, boost nutrient's absorption and improve gastrointestinal functionality
*MMPs↓, They postulated that inhibition of interlukon, matrix metalloproteinase, prostaglandin E2, and activator protein 1 are possible routes for their said properties
*PGE2↓,
*AP-1↓,
*5LO↓, Piperine along with some other components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that
are responsible for leukotriene and prostaglandin biosynthesis.
*COX1↓,
*other↑, It is widely accepted that black pepper is instrumental to prevent and cure gastrointestinal problems. The black pepper enhances the production of hydrochloric acid from stomach thus improving digestion through stimulation of histamine H2 recepto
*other↑, black pepper has diaphoretic (promotes sweating), and diuretic (promotes urination) properties
*other↑, Moreover, it protects intestinal membranes from gastric secretions and ROS damage owing to antioxidant potential.
*SOD↑, black pepper significantly enhanced the activities of antioxidant enzymes, that is, SOD, CAT, GR, and GST.
*Catalase↑,
*GSTs↑,
*GSR↑,
*other↑, black pepper and its active ingredients improve expression of
some digestive enzymes along with increase in the secretion of
saliva
*Weight↓, piperine intake may decrease body weight
*BioEnh↑, The black pepper and piperine improve the bioavailability of many drugs.
*BioAv↑, Piperine also boosts the bioavailability of important phyto-
chemicals contained in other foods, for example, bioactive com-
ponents present in curcumin and green tea
*eff↑, The combination of piperine (2.5 mg/kg, i.p., 21 days) with curcumin (20 and 40 mg/kg, i.p., 21 days) showed improved anti-immobility, neurotransmitter enhancing, and monoamine oxidase inhibitory (MAO-A) effects of curcumin
*CYP3A2↓, combination of curcumin and piperine is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa (Volak et al., 2008)
*neuroP↑, Neuroprotective Potential of Black Pepper
*BP↓, Piperine (20 mg/kg/day) decreased
the blood pressure caused by the blockage of voltage-dependent
calcium channels
*other↑, black pepper oil is one of the strongest appetizer; inhalation stimulates the swallowing
in post stroke patients with dysphagia.
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*antiOx↑, shown to possess various pharmacological properties including antioxidant, free radical scavenging, anti-inflammatory, analgesic, antispasmodic, antibacterial, antifungal, antiseptic and antitumor activities.
*ROS↓,
*Inflam↓,
*Bacteria↓,
AntiTum↑,
IronCh↑, chelation of metal ions
*HDL↑, antihyperlipidemic (via increasing the levels of high density lipoprotein cholesterol and decreasing the levels of low density lipoprotein cholesterol
*LDL↓,
*BioAv↝, videnced the presence of thymol in the stomach, intestine, and urine after its oral administration with sesame oil at a dose around 500 mg in rats and 1–3 g in rabbits.
*Half-Life↝, Oral administration of a single dose of thymol (50 mg/kg) was rapidly absorbed and slowly eliminated approximately within 24 h.The maximum concentration (Tmax) was reached after 30 min, while approximately 0.3 h was needed for the half-life
*BioAv↑, The rapid absorption of thymol indicates that it’s mainly absorbed in the upper component of the gut
*SOD↑, scavenging of free radicals by increasing the activities of several endogenous antioxidant enzymes levels viz. superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST)
*GPx↑,
*GSTs↑,
*eff↑, Thymol (0.02–0.20%) showed better antioxidant capacity than its isomer carvacrol in lipid systems due to its greater steric hindrance
radioP↑, Owing to its potent antioxidant potential, thymol showed radioprotective and anticlastogenic potential in gamma radiation induced Swiss albino mice
*MDA↓, Thymol supplementation increased the antioxidant status and decreased malondialdehyde (MDA) levels in broiler chickens
*other↑, Dietary supplementation with the combination of carvacrol–thymol (1:1) (100 mg/kg) reduced the occurrence of oxidative stress and the impairment of the intestinal barrier in weaning piglets by its potent antioxidant property
*COX1↓, by inhibiting both isoforms of cyclooxygenase (COX), with the most active being against COX-1 with an IC50 value of 0.2 μM.
*COX2↓,
*AntiAg↑, Thymol (1.1 μg/ml) exhibited inhibitory effects against arachidonic-acid-induced blood coagulation and platelet aggregation in vitro
*RNS↓, Thymol inhibited ROS (IC50= 3 μg/ml), reactive nitrogen species (RNS) (IC50= 4.7) and significantly reduced generation of NO and H2O2 as well as activities of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide reduced oxidase (NADH oxi
*NO↓,
*H2O2↓,
*NOS2↓,
*NADH↓,
*Imm↑, Thymol (25–200 mg/kg) was shown to modulate the immune system in cyclosporine-A treated Swiss albino mice by enhancing the expressions of cluster of differentiation 4 (CD4),
Apoptosis↑, anticancer actions of thymol include induction of apoptosis, anti-proliferation, inhibition of angiogenesis and migration
TumCP↓,
angioG↓,
TumCMig↓,
Ca+2↑, Intracellular Ca2+ overload
TumCCA↑, Cytotoxicity by stimulating cell cycle arrest in G0/G1 phase
DNAdam↑, DNA fragmentation, Bax protein expression, activation of caspase -9, -8 and -3 & concomitant PARP cleavage, AIF translocation
BAX↑,
Casp9↑,
Casp8↑,
Casp3↑,
cl‑PARP↑,
AIF↑,
i-ROS↑, intracellular ROS, depolarizing MMP, cytochrome-c release, cleavage of caspases, DNA fragmentation, activation of apaf-1,
MMP↓,
Cyt‑c↑,
APAF1↑,
Ca+2↑, In human glioblastoma cells, thymol (200–600 μM) produced a rise in (Ca2+)i levels
MMP9↓, diminished matrix metallopeptidase-9 (MMP9) and matrix metallopeptidase-2 (MMP2) production as well as protein kinase Cα (PKCα) and extracellular signal-regulated kinases (ERK1/2) phosphorylation
MMP2↓,
PKCδ↓,
ERK↓,
H2O2↑, Thymol increased the production of ROS and mitochondrial H2O2 thereby depolarizing mitochondrial membrane potential.
BAX↑, up-regulating Bcl-2 associated X protein (Bax) expression and down-regulating B-cell lymphoma (Bcl-2)
Bcl-2↓,
DNAdam↑, Thymol (IC50= 497 and 266 mM) was shown to induce DNA damage by increasing the levels of lipid peroxidation products;
lipid-P↑,
ChemoSen↑, This study recommended the combination of thymol with various chemotherapeutic agents to minimize its toxicity on normal cells and to improve the effectiveness of cancer treatment
chemoP↑,
*cardioP↑, significant increase in the activities of heart mitochondrial antioxidants (SOD, catalase, GPx, GSH)
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*BP↓, Thymol (1, 3, and 10 mg/kg) administration decreased the blood pressure and heart rate of Wistar rats whereas thymol (5 mg/kg) attenuated blood pressure in rabbits
*AntiDiabetic↑, protective effects of thymol in metabolic disorders such as diabetes mellitus and obesity
*Obesity↓,
RenoP↑, Thymol (20 mg/kg) was shown to inhibit cisplatin-induced renal injury by attenuating oxidative stress, inflammation and apoptosis in male adult Swiss Albino rats
*GastroP↑, This gastroprotective effect of thymol is believed to be due to increased mucus secretion
hepatoP↑, Thymol (150 mg/kg) showed to inhibit paracetamol induced hepatotoxicity in mice by preventing the alterations in the activities of hepatic marker enzymes
*AChE↓, Thymol (EC50= 0.74 mg/mL) was shown to possess acetylcholine esterase inhibitory activity but much less than its isomer carvacrol
*cognitive↑, Thymol (0.5–2 mg/kg) has been shown to inhibit cognitive impairments caused by increased Aβ levels or cholinergic hypofunction in Aβ
*BChE↓, whereas thymol (100 and 1000 μg/ml) also inhibited both AChE and butyrylcholinesterase (BChE) in a dose dependent manner
*other↓, Thymol (100 mg/kg) was shown to inhibit collagen induced arthritis by decreasing lipid peroxidation mediated oxidative stress by increasing the status of antioxidants in male Wistar rats
*BioAv↑, The encapsulation of thymol into methylcellulose microspheres by spray drying remarkably increases the bioavailability compared to free thymol
Showing Research Papers: 1 to 26 of 26
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 26
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 1, H2O2↑, 1, HO-1↓, 1, HO-2↓, 1, lipid-P↑, 1, ROS↓, 1, ROS↑, 5, i-ROS↑, 1,
Metal & Cofactor Biology ⓘ
IronCh↑, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 3, CDC25↓, 1, ETC↓, 1, MMP↓, 2, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AMPK↓, 1, AMPK↑, 1, cMyc↓, 3, ECAR↝, 1, GlucoseCon↓, 1, Glycolysis↓, 1, lactateProd↓, 1, PDK1?, 2, SIRT1↓, 1,
Cell Death ⓘ
Akt↓, 3, Akt↑, 1, p‑Akt↓, 2, APAF1↑, 1, Apoptosis↑, 3, BAX↑, 2, Bax:Bcl2↑, 1, Bcl-2↓, 1, Bcl-xL↓, 1, Casp3↑, 3, Casp8↑, 3, Casp9↑, 2, Cyt‑c↑, 3, Diablo↑, 2, DR5↑, 1, Fas↑, 1, FasL↑, 1, ICAD↓, 1, iNOS↓, 1, JNK↑, 1, Mcl-1↓, 1, MDM2↓, 1, Myc↓, 1, NOXA↑, 1, PUMA↑, 1, survivin↓, 2, Telomerase↓, 1, TRPV1↑, 1,
Kinase & Signal Transduction ⓘ
SOX9↓, 1,
Transcription & Epigenetics ⓘ
other↓, 1, other↑, 2, tumCV↓, 1,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, ER Stress↑, 1, GRP78/BiP↑, 1, HSP90↓, 1,
Autophagy & Lysosomes ⓘ
BNIP3↝, 1, TumAuto↑, 1,
DNA Damage & Repair ⓘ
DNAdam↓, 1, DNAdam↑, 3, DNArepair↑, 1, P53↑, 2, cl‑PARP↑, 3, PCNA↓, 1, SIRT6↑, 1,
Cell Cycle & Senescence ⓘ
p‑CDK1↓, 1, CDK2↓, 1, cycD1/CCND1↓, 2, cycE/CCNE↓, 1, P21↑, 3, p‑RB1↓, 2, TumCCA↑, 4,
Proliferation, Differentiation & Cell State ⓘ
CDK8↓, 2, CSCs↓, 1, EMT↓, 3, ERK↓, 1, p‑ERK↓, 2, FOXM1↓, 1, FOXO↑, 1, GSK‐3β↓, 1, mTOR↓, 1, NOTCH↓, 2, P90RSK↓, 1, PI3K↓, 2, PTEN↑, 1, Shh↓, 1, STAT3↓, 3, p‑STAT3↓, 1, TOP2↓, 1, TumCG↓, 1, Wnt↓, 1, Wnt/(β-catenin)↓, 1,
Migration ⓘ
5LO↓, 1, AntiAg↑, 3, Ca+2↑, 2, Ca+2↝, 1, cal2↓, 1, E-cadherin↑, 1, p‑FAK↓, 1, MMP2↓, 5, MMP9↓, 6, PKCδ↓, 2, Slug↓, 1, SMAD3↓, 1, Snail↓, 2, TGF-β↓, 2, TumCI↓, 2, TumCMig↓, 2, TumCP↓, 4, TumMeta↓, 4, Twist↓, 3, Vim↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 4, EGFR↓, 1, Endoglin↑, 1, Hif1a↓, 2, TXA2↓, 2, VEGF↓, 4,
Barriers & Transport ⓘ
NHE1↓, 1,
Immune & Inflammatory Signaling ⓘ
COX1↓, 12, COX2↓, 5, IL6↓, 1, Inflam↓, 2, JAK↓, 1, NF-kB↓, 5, PD-L1↓, 2, PGE2↓, 2,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1, CDK6↓, 2,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, ChemoSen↑, 4, Dose↑, 1, Dose↝, 2, Dose∅, 1, eff↑, 4, RadioS↑, 6, selectivity↑, 2,
Clinical Biomarkers ⓘ
ALAT↓, 1, ALP↓, 1, AR↓, 1, AST↓, 1, CTC↓, 1, EGFR↓, 1, FOXM1↓, 1, GutMicro↑, 1, IL6↓, 1, Myc↓, 1, PD-L1↓, 2,
Functional Outcomes ⓘ
AntiTum↑, 1, cardioP↑, 1, chemoP↑, 2, hepatoP↑, 1, radioP↑, 1, RenoP↑, 1, Risk↓, 6,
Total Targets: 160
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 4, Catalase↑, 4, GPx↑, 3, GSH↑, 3, GSR↑, 1, GSTs↑, 2, H2O2↓, 1, HDL↑, 1, HO-1↑, 2, lipid-P↓, 1, MDA↓, 2, NADH↓, 1, NRF2↓, 1, Prx↑, 1, RNS↓, 1, ROS↓, 5, SOD↑, 5,
Mitochondria & Bioenergetics ⓘ
MMP↑, 1,
Core Metabolism/Glycolysis ⓘ
12LOX↑, 1, CYP3A2↓, 1, LDL↓, 1,
Cell Death ⓘ
Akt↓, 1, Casp3↓, 1, Casp9↓, 1, Cyt‑c↓, 1, iNOS↓, 1, p‑JNK↓, 1, MAPK↓, 1, p38↓, 1,
Transcription & Epigenetics ⓘ
other?, 1, other↓, 1, other↑, 9, other↝, 3,
Protein Folding & ER Stress ⓘ
HSP70/HSPA5↑, 1, HSPs↑, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↓, 1, PI3K↓, 1,
Migration ⓘ
5LO↓, 3, AntiAg↓, 1, AntiAg↑, 7, AP-1↓, 3, MMP13↓, 1, MMP3↓, 1, MMP9↓, 2, MMPs↓, 1, TGF-β↓, 1, α-SMA↓, 1,
Angiogenesis & Vasculature ⓘ
LOX1↓, 1, NO↓, 2, NO↑, 1, TXA2↓, 3,
Barriers & Transport ⓘ
BBB↑, 1, GastroP↑, 1,
Immune & Inflammatory Signaling ⓘ
COX1↓, 14, COX2↓, 8, CRP↓, 1, CXCR4↓, 1, IL10↑, 1, IL17↓, 1, IL18↓, 1, IL1β↓, 3, IL4↑, 1, IL6↓, 3, IL8↓, 1, Imm↑, 1, Inflam↓, 8, NF-kB↓, 2, PGE2↓, 4, PGE2↑, 1, Th1 response↓, 1, Th2↑, 2, TLR4↓, 1, TNF-α↓, 3,
Synaptic & Neurotransmission ⓘ
AChE↓, 1, BChE↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, BioAv↑, 5, BioAv↝, 2, BioEnh↑, 2, Dose⇅, 1, eff↑, 2, eff↝, 1, Half-Life↓, 3, Half-Life↝, 1,
Clinical Biomarkers ⓘ
BP↓, 2, CRP↓, 1, IL6↓, 3, NOS2↓, 1,
Functional Outcomes ⓘ
AntiDiabetic↑, 1, cardioP↑, 5, chemoP↑, 1, cognitive↑, 2, hepatoP↑, 1, neuroP↑, 3, Obesity↓, 1, toxicity↓, 1, toxicity∅, 1, Weight↓, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1,
Total Targets: 99
Scientific Paper Hit Count for: COX1, COX-1
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:% Target#:998 State#:% Dir#:1
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