Celecoxib / cJun Cancer Research Results

CEL, Celecoxib: Click to Expand ⟱
Features: NSAID
Celecoxib inhibits the formation of prostaglandins: used primarily to treat pain and other symptoms of osteoarthritis, rheumatoid arthritis, joint and musculoskeletal conditions.

Celecoxib is a diaryl-substituted selective cyclooxygenase-2 inhibitor that lowers prostaglandin synthesis and is used clinically as an oral nonsteroidal anti-inflammatory drug. It is formally classified as a small-molecule NSAID and COX-2–preferential inhibitor. Standard abbreviations include celecoxib and CEL. In oncology, its main rationale is suppression of the COX-2/PGE2 inflammatory-tumor axis, with additional COX-2-independent effects reported at higher experimental concentrations, including interference with PDK1/Akt signaling, ER calcium handling, and stress-linked apoptosis pathways. NSAID and indexes mainly EMT, HIF-1α/VEGF, COX-2, NF-κB, p65, and TGF-β/SMAD3-related findings.

Primary mechanisms (ranked):

  1. COX-2 inhibition with reduced PGE2 signaling and downstream inflammatory, proliferative, angiogenic, and immune-evasive tumor support
  2. Suppression of NF-κB-linked inflammatory survival programs
  3. Reduction of hypoxia/angiogenesis signaling including HIF-1α and VEGF in relevant models
  4. Partial inhibition of PDK1/Akt survival signaling in some tumor systems
  5. COX-2-independent ER stress and Ca²⁺ dysregulation via SERCA-related effects at supratherapeutic or high in-vitro concentrations
  6. Contextual chemosensitization, including effects on apoptosis threshold and in some reports drug-resistance programs such as P-gp
  7. Possible ancillary carbonic anhydrase inhibition is mechanistically interesting but not established as the dominant clinical anticancer mechanism

Bioavailability / PK relevance: Celecoxib is orally active. Peak plasma levels occur at about 3 hours, effective half-life is about 11 hours, steady state is reached by about day 5, and the drug is highly protein bound. Exposure is roughly dose-proportional up to 200 mg twice daily, with less-than-proportional increases above that range because of solubility limits. It is metabolized mainly by CYP2C9, so poor metabolizers and strong CYP2C9 interactions are clinically relevant.

In-vitro vs systemic exposure relevance: This is an important translation constraint. Many direct pro-apoptotic, SERCA/ER-stress, and stronger Akt-related anticancer effects are reported in vitro at concentrations commonly above those readily achievable with standard anti-inflammatory dosing. By contrast, COX-2/PGE2 suppression is clearly clinically reachable and is the most exposure-plausible core mechanism. Therefore, low- to mid-micromolar inflammatory and microenvironment effects are more translatable than high-concentration cytotoxic claims.

Clinical evidence status: Strong clinical deployment exists for pain/inflammatory indications, not for cancer treatment. In oncology, evidence is mixed: extensive preclinical support, some small human and adjunct studies, but major randomized adjuvant trials in unselected breast and stage III colon cancer were negative overall. A more recent biomarker-defined signal has emerged in PIK3CA-activated stage III colon cancer, where celecoxib appeared beneficial in subgroup analysis, so any cancer role currently looks biomarker- and context-dependent rather than broadly established.

Mechanistic table

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 COX-2 / PGE2 inflammatory signaling COX-2 activity ↓; PGE2 tone ↓; proliferation, survival, invasion, immune evasion ↓ Inflammatory prostaglandin signaling ↓ R/G Core anti-inflammatory antitumor mechanism Best-supported and most clinically reachable mechanism; strongest translational anchor for oncology repurposing
2 NF-κB inflammatory survival axis NF-κB/p65 ↓; inflammatory survival transcription ↓ Inflammatory signaling ↓ R/G Reduced survival and inflammatory tone partly downstream of reduced PGE2 but may also reflect parallel signaling effects
3 HIF-1α / VEGF angiogenesis axis HIF-1α ↓; VEGF ↓; angiogenic support ↓ ↔ or angiogenic signaling ↓ in inflammatory settings G Antiangiogenic pressure Likely relevant in hypoxic and COX-2-high tumors; fits broader COX-2/PGE2 biology
4 TGF-β / SMAD3 / EMT TGF-β ↓; SMAD3 ↓; EMT ↓; migration/invasion ↓ ↔ G Anti-migratory and anti-invasive effect likely more tumor-contextual than universally dominant
5 PDK1 / Akt survival signaling PDK1/Akt ↓ (context-dependent); apoptosis threshold ↓ ↔ R/G COX-independent survival suppression Mechanistically important in the celecoxib literature, but many strong effects are reported at higher in-vitro concentrations
6 Ca²⁺ homeostasis and ER stress ER Ca²⁺ reuptake ↓; cytosolic Ca²⁺ stress ↑; ER stress/apoptosis ↑ Potential stress if exposure is high enough P/R Stress-triggered apoptosis Usually linked to SERCA interference and considered mainly a high-concentration or COX-independent mechanism
7 Mitochondrial apoptosis program Caspase activation ↑; Bcl-2-family survival balance shifts toward apoptosis ↔ R/G Apoptotic execution Generally downstream of Akt inhibition, ER stress, or combined treatment sensitization rather than the first initiating event
8 Chemosensitization Drug sensitivity ↑; apoptosis with cytotoxics ↑ Potential inflammation/pain benefit in host context G Adjunctive therapy potential Observed preclinically and in some clinical adjunct settings, but not confirmed as a broad survival-improving strategy in unselected populations
9 P-gp and resistance signaling P-gp ↓ (model-dependent); intracellular drug retention ↑ ↔ G Possible reversal of drug resistance Interesting but not core; should be treated as secondary and context-specific
10 Carbonic anhydrase inhibition CA-related pH adaptation ↓ (context-dependent) Off-target CA interaction possible ↔ Ancillary microenvironment effect Celecoxib can inhibit carbonic anhydrases, but this is better viewed as a mechanistic side branch than the main oncology rationale for celecoxib itself
11 Clinical Translation Constraint Overall efficacy signal mixed; biomarker-defined benefit more plausible than broad use Cardiovascular, renal, GI, and drug-interaction liabilities constrain chronic escalation G Limits generalized oncology deployment Main constraint is that clinically achievable exposure strongly supports COX-2/PGE2 modulation, whereas many direct cytotoxic claims require higher concentrations; major adjuvant trials were negative overall, though PIK3CA-activated colon cancer is a notable exception signal

P: 0–30 min

R: 30 min–3 hr

G: >3 hr
cJun, cellular Transcription factor Jun: Click to Expand ⟱
Source:
Type: Oncogene
Transcription factor Jun is a protein that in humans is encoded by the JUN gene.
Increased c-jun gene and c-Jun protein expression, and stimulation of c-Jun phosphorylation has been noted under a variety of conditions. Most important member of the AP-1 transcription factor family.
Scientific Papers found: Click to Expand⟱
5954- CEL,    The molecular mechanisms of celecoxib in tumor development
- Review, Var, NA
TumCP↓, Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis
TumCMig↓,
TumCI↓,
COX2/PTGS2↓,
p‑NF-kB↓, thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
Akt↓,
MMP2↓,
MMP9↓,
Apoptosis↑, celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy.
mitResp↑,
ER Stress↑,
TumAuto↑,
ChemoSen↑, Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.
Inflam↓, NSAIDs achieve anti-inflammatory effects by inhibiting the activity of the inflammatory factor COX-2 and the synthesis of PGE2.
PGE2↓,
chemoPv↑, Numerous studies have confirmed that NSAIDs also have chemopreventive effects on tumors.
toxicity↓, Compared with other NSAIDs, celecoxib shows lower toxicity side effects (such as the most common gastrointestinal bleeding and gastric ulcer).[
Risk↓, Early studies have shown that celecoxib can effectively reduce the incidence of colorectal cancer, especially inhibiting the development of familial adenomatous polyposis to colorectal cancer.
PI3K↓, celecoxib can promote cancer cell apoptosis by inhibiting the signal pathway of 3-phosphoinositide-dependent kinase-1 and downstream protein kinase B (Akt) in human colon cancer cells.
RadioS↑, celecoxib enhances the sensitivity of cancer cells to radiation therapy
TumCMig↓, inhibits cancer cell migration and invasion by inhibiting the activity of C-Jun amino-terminal kinase and downregulating the expression of specific protein 1.
TumCI↓,
cJun↓,
Sp1/3/4↓,
ROS↑, Celecoxib targets mitochondria and promotes the release of ROS by significantly increased oxidative stress.
MMP↓, lead to the decrease of cell consumption and mitochondrial transmembrane potential (△ ψ m), increasing mitochondrial membrane permeability to promote the release of ROS
MPT↑,
Ca+2↑, promote Ca2+ influx, produce a higher pro-oxidation state, increase the accumulation of ROS in cancer cell mitochondria,
Glycolysis↓, inhibits the glycolysis process, ATP synthesis is significantly reduced, leading to cancer cell death.[
ATP↓,
CSCs↓, In addition to cancer cells, celecoxib can also inhibit CSCs.
Wnt/(β-catenin)↓, celecoxib can inhibit the transduction of Wnt/β-catenin signaling pathway
EMT↓, celecoxib can inhibit the process of EMT
toxicity↝, ong-term use increases the risk of hypertension among participants who already have cardiovascular risk factors.[


Showing Research Papers: 1 to 1 of 1

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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mitResp↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ATP↓, 1,   Glycolysis↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 1,   PI3K↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

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

CSCs↓, 1,   TumCP↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   EMT↓, 1,   MMP2↓, 1,   MMP9↓, 1,   TumCI↓, 2,   TumCMig↓, 2,  

Barriers & Transport(tgid=15) ⓘ

MMP↓, 1,   MPT↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Inflam↓, 1,   p‑NF-kB↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   RadioS↑, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,   Risk↓, 1,   toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: cJun, cellular Transcription factor Jun
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#:4  Target#:34  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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