Auranofin / eff Cancer Research Results

AF, Auranofin: Click to Expand ⟱

Features:

Auranofin — an orally administered gold(I) coordination complex (gold–phosphine–thiolate “thiosugar” drug) originally approved as a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis and widely studied for repurposing as a redox-targeted anticancer and anti-infective agent. It is a small-molecule metallodrug whose pharmacology is typically tracked via blood/plasma gold concentrations because intact auranofin is rapidly transformed and not reliably detected in blood. Standard abbreviation(s): AF (auranofin); primary target shorthand: TrxR/TxNRD (thioredoxin reductase).

Primary mechanisms (ranked):

Thioredoxin reductase (TXNRD1/TXNRD2; TrxR) inhibition by gold(I) → thioredoxin system suppression and loss of redox-buffering capacity
ROS and redox stress escalation (secondary to TrxR blockade; often NAC-reversible in models) → apoptosis and other regulated death programs
Mitochondrial dysfunction (Δψm collapse, bioenergetic stress) coupled to redox imbalance
Proteostasis stress (ER stress/UPR; proteasome involvement in selected contexts) → non-apoptotic death phenotypes (model-dependent)
Ferroptosis contribution in subsets of models (lipid peroxidation–dependent; context-dependent)
Radiosensitization / chemosensitization via impaired antioxidant recovery and enhanced oxidative injury (context-dependent)
Stress-response transcription (e.g., NRF2 activation as an adaptive resistance program in some settings; protective in normal cells)

Bioavailability / PK relevance: Oral absorption is incomplete; clinical PK is commonly described as ~25% of the gold content absorbed. Gold is highly protein-bound and exhibits prolonged retention/long terminal half-life, so effective exposure depends strongly on dose and dosing duration. Because “gold levels” are the main measurable surrogate, cross-study comparisons should specify matrix (whole blood vs plasma) and timing (steady-state vs short course).

In-vitro vs systemic exposure relevance: Many oncology cell studies use ~0.5–5 µM AF. Human short-course data at 6 mg/day for 7 days report plasma gold on the order of ~0.1–0.3 µg/mL (roughly sub-µM to ~1–1.5 µM range when expressed as gold equivalents), meaning lower in-vitro ranges can overlap clinically observed exposure surrogates, while higher µM regimens may exceed typical oral exposures unless higher doses/longer courses or formulation changes are used.

Clinical evidence status: Approved for rheumatoid arthritis (historical DMARD use) but oncology use remains investigational. Multiple early-phase repurposing trials exist across hematologic and solid tumors; several completed studies have limited publicly posted outcomes, and there is no established standard-of-care anticancer indication.

Pathways:
1.Thioredoxin Reductase (TrxR) Inhibition.
- Most widely recognized for potently inhibiting TrxR.
2.Induction of Reactive Oxygen Species (ROS) and Oxidative Stress.
3.MMP depolarization, release of cytochrome c
4.Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR)
5.Inhibition of Pro-survival Pathways (e.g., NF-κB Signaling)

-ic50 for cancer typically 1-3uM, normal cell 5-10uM or higher.
-Several studies animal testing antitumor efficacy have used doses in the region of 5–8 mg/kg via intraperitoneal injection or oral administration.

-Auranofin’s anticancer activity is often linked to its inhibition of thioredoxin reductase, leading to increased oxidative stress.

Mechanistic axes for Auranofin (Cancer vs Normal)

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	TXNRD1 TXNRD2 Thioredoxin system	↓ (primary)	↓ (primary)	P→R	Collapse of thioredoxin redox buffering	Core, proximal target of AF; downstream effects track with redox reserve and compensatory antioxidant capacity rather than tumor lineage alone.
2	ROS redox stress	↑ (often primary downstream)	↑ (dose-dependent)	P→R	Oxidative injury signaling and death pathway engagement	Frequently reversible with thiol antioxidants (e.g., NAC) in models, supporting causality; magnitude depends on baseline redox fragility.
3	Mitochondria bioenergetics	Δψm ↓, ATP stress ↑ (context-dependent)	Δψm ↓ (dose-dependent)	R	Energetic crisis and intrinsic death susceptibility	Often coupled to redox imbalance; can amplify apoptosis/regulated necrosis depending on cellular checkpoints.
4	Proteostasis ER stress UPR	↑ (model-dependent)	↔/↑ (high exposure only)	R→G	Protein-folding overload and non-apoptotic death phenotypes	Some reports implicate proteasome participation and paraptosis-like outcomes; not universal across tumor types.
5	NRF2 antioxidant response	↑ (adaptive; resistance role)	↑ (cytoprotective)	R→G	Transcriptional compensation to redox stress	NRF2 induction can blunt AF efficacy in tumors yet protect normal tissues; net effect is (context-dependent).
6	Ferroptosis lipid peroxidation	↑ (model-dependent)	↔/↑ (stress-prone contexts)	R→G	Regulated death component in subsets	Most consistent when AF-driven redox stress converges on lipid ROS handling; requires model-specific validation.
7	Radiosensitization chemosensitization	↑ sensitivity (context-dependent)	↑ toxicity risk (context-dependent)	R→G	Impaired antioxidant recovery increases treatment injury	Mechanistically coherent with TrxR blockade; best supported where oxidative damage markers and combination indices are shown.
8	Ca²⁺ stress coupling	↑/↔ (secondary)	↑/↔ (secondary)	R	Amplifies ER mitochondrial death signaling	Usually downstream of redox + organelle perturbation; include when Ca²⁺-dependent apoptosis/ER stress is explicitly demonstrated.
9	Glycolysis ATP production	↓ (context-dependent)	↔/↓ (high exposure only)	R	Metabolic stress that can reduce proliferative fitness	Reported in some models; may be secondary to mitochondrial/redox disruption rather than a primary binding target.
10	HIF-1α hypoxia programs	↔ (model-dependent)	↔	G	Context marker rather than core axis	Evaluate case-by-case; AF’s primary leverage is redox enzyme inhibition, with HIF effects emerging indirectly in some systems.
11	Clinical Translation Constraint	↔	↔	—	Exposure, tolerability, and selectivity limit window	Oral absorption is incomplete and gold is long-retained/protein-bound; many oncology studies rely on µM in-vitro dosing that may exceed typical oral exposure surrogates. Oncology trials exist but anticancer efficacy is not established as standard-of-care.

TSF legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr

eff, efficacy: Click to Expand ⟱

Source:

Type:

Power to enhance an anti cancer effect

Scientific Papers found: Click to Expand⟱

5472-

AF,

Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion

in-vitro,

Cerv,

HeLa

TrxR↓, AntiCan↑, TumCG↓, Apoptosis↑, necrosis↑, cl‑PARP↑, MMP↓, ROS↑, GSH↓, eff↓,

5469-

AF,

Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation

in-vitro,

CRC,

HCT116

eff↑, Half-Life↑,

5468-

AF,

The gold complex auranofin: new perspectives for cancer therapy

Review,

Var,

TrxR↓, ROS↑, eff↑, Apoptosis↑, TumCG↓, TumCP↓, Akt↓, NF-kB↓, DNAdam↑, eff↝, eff↓, PI3K↓, Akt↓, mTOR↓, Hif1a↓, VEGF↓, Casp3↑, CSCs↓, ATP↓, Glycolysis↓, eff↑, eff↑, MMP↓, AIF↑, toxicity↓,

5467-

AF,

Auranofin Inhibition of Thioredoxin Reductase Sensitizes Lung Neuroendocrine Tumor Cells (NETs) and Small Cell Lung Cancer (SCLC) Cells to Sorafenib as well as Inhibiting SCLC Xenograft Growth

in-vitro,

Lung,

DMS53 human small cell lung cancer cells

TrxR↓, eff↑, Dose↝, OS↑, eff↑,

5464-

AF,

Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies

vitro+vivo,

GBM,

TrxR↓, BioAv↓, ROS↑, eff↝, TET1?, BioAv↑,

5460-

AF,

Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species

vitro+vivo,

Var,

4T1

RadioS↑, ROS↑, eff↓, mt-OCR↓, DNAdam↑, Apoptosis↑, TrxR↓, eff↑,

5459-

AF,

Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

in-vitro,

Ovarian,

ROS↑, TrxR↓, MMP↓, Apoptosis↑, eff↓, Casp3↑, Casp7↑, DNAdam↑, eff↑, GSH↓, angioG↓, ChemoSen↑, cl‑PARP↑, eff↑,

5458-

AF,

Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer

in-vitro,

NSCLC,

TrxR↓, AntiCan↓, GPx4↓, DNAdam↑, toxicity↓, eff↝,

1900-

AF,

Potential Anticancer Activity of Auranofin

Review,

Var,

TrxR↓, ROS↑, Apoptosis↓, TumCP↓, eff↑,

2951-

PL,

AF,

Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells

in-vitro,

GBM,

U87MG

GSH↓, eff↑, GSTP1/GSTπ↓,

1459-

SFN,

AF,

Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway

in-vitro,

Liver,

Hep3B

 auranofin (0.5, 1, 1.5, and 2 μM) or sulforaphane (2.5, 5, 7.5, and 10 μM)

in-vitro,

Liver,

HepG2

eff↑, TumCCA↑, Apoptosis↑, MMP↓, BAX↑, cl‑PARP↑, Casp3↑, Casp8↑, Casp9↑, ROS↑, eff↓, PI3K↓, Akt↓, TrxR↓, BAX↑, Bcl-2∅,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: eff, efficacy

11 Auranofin
1 Piperlongumine
1 Sulforaphane (mainly Broccoli)

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#:273  Target#:961  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Auranofin / eff Cancer Research Results

Mechanistic axes for Auranofin (Cancer vs Normal)

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

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