Copper and Cu NanoParticles / ROS Cancer Research Results

Cu, Copper and Cu NanoParticles: Click to Expand ⟱
Features:
Copper
Metal
Copper levels are considerably elevated in various malignancies.
Copper [Cu(II)] is a transition and trace element in living organisms. It increases reactive oxygen species (ROS) and free-radical generation that might damage biomolecules like DNA, proteins, and lipids.
RDA: 900 mcg, ULs: 10,000mcg

Copper (dietary/physiology) ≠ copper-loading therapeutics ≠ copper nanoparticles.
For Cu nanoparticles, the dominant and most reproducible theme is toxicity via ROS → mitochondrial damage/genotoxicity, not clean tumor selectivity.
- Copper acts as a critical cofactor for numerous enzymes involved in redox reactions, energy production, and connective tissue formation.
- Increased copper levels in the tumor microenvironment can enhance angiogenic signaling and thus supply the tumor with necessary oxygen and nutrients, facilitating tumor growth and metastasis.
- Copper can participate in redox cycling reactions, similar to the Fenton reaction, leading to the production of reactive oxygen species (ROS).
- Cancer cells often exhibit altered copper homeostasis, with some studies showing elevated copper levels in tumor tissues relative to normal tissues.

Copper serves a dual role in cancer: Imbalanced copper metabolism promotes tumor cell proliferation and survival by activating the receptor tyrosine kinase, PI3K/Akt/mTOR, and MAPK/ERK signaling pathways, while cuproptosis suppresses tumor growth by inducing cell death and activating immune responses

Two main approaches are:
- Copper Chelation: Drugs that bind copper (chelators) can reduce the bioavailability of copper, potentially inhibiting angiogenesis and other copper-dependent tumor processes.
- Copper Ionophores: These agents facilitate the transport of copper into cancer cells to induce cytotoxicity by elevating intracellular copper levels beyond a tolerable threshold, leading to cell death.

- Depletion of glutathione and stimulation of lipid peroxidation, catalase and superoxide dismutase.
- Studies have shown that the level of copper in tumour cells and blood serum from cancer patients is elevated, and the conclusion is that cancer cells need more copper than healthy cells. (but also sometimes depleted).
- Copper is a double-edged sword, maintaining normal cell development and promoting tumor development.
- Tumor tissue has a higher demand for copper and is more susceptible to copper homeostasis, copper may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition and anti-angiogenesis.

Copper and Cu NanoParticles — Copper is an essential redox-active trace metal and transition element that becomes oncology-relevant through copper homeostasis, copper-dependent enzymes, copper chelation, copper ionophore/copper-loading strategies, and copper-based nanoparticles. The formal classification is mixed: elemental/ionic metal biology, copper coordination chemistry, micronutrient/mineral exposure, and inorganic/nano-oncology modality. Standard abbreviations include Cu, Cu(I), Cu(II), CuNP, CuO-NP, Cu2O-NP, DSF/Cu, and TM for tetrathiomolybdate. The most important distinction is that dietary copper physiology, therapeutic copper depletion, copper ionophore loading, copper complexes, and copper nanoparticles are not interchangeable exposures.

Primary mechanisms (ranked):

  1. Copper homeostasis disruption and cuproptosis: intracellular Cu accumulation can bind lipoylated mitochondrial TCA-cycle proteins, promote protein aggregation, reduce Fe-S protein integrity, and trigger proteotoxic mitochondrial cell death.
  2. Copper-dependent tumor biology: copper availability supports angiogenesis, ECM remodeling, invasion/metastasis programs, and copper-requiring enzymes such as LOX/LOXL and SOD1.
  3. CuNP and CuO-NP oxidative cytotoxicity: particle dissolution/surface chemistry and released Cu ions can increase ROS, mitochondrial injury, DNA damage, apoptosis, inflammation, and lipid peroxidation.
  4. Copper chelation: copper depletion can suppress angiogenesis and tumor microenvironment support, but excessive depletion creates systemic deficiency risk.
  5. Copper ionophore or copper-loading strategies: agents such as disulfiram/copper can increase intracellular copper stress and sensitize some models, but clinical results are inconsistent and toxicity can increase.
  6. Redox and GSH axis: copper can amplify oxidative stress and deplete thiol buffering; this is mechanistically central for CuNP/CuO-NP toxicity and context-dependent for copper complexes or ionophores.
  7. Radiosensitization or chemosensitization: reported mainly in preclinical or early clinical DSF/Cu and copper-complex contexts, not established as a standard oncology treatment.

Bioavailability / PK relevance: Oral nutritional copper is normally tightly regulated by absorption, biliary excretion, ceruloplasmin binding, and intracellular chaperones. Copper nanoparticles and copper oxide nanoparticles have distinct PK and toxicology constraints because particle size, coating, dissolution, route of exposure, aggregation, and organ deposition can dominate exposure. Copper chelation requires systemic copper lowering, while copper-loading strategies require sufficient intracellular Cu delivery without unacceptable normal-tissue toxicity.

In-vitro vs systemic exposure relevance: Many CuNP/CuO-NP anticancer experiments use direct cell-culture concentrations that may exceed safe or achievable systemic exposure and may reflect non-selective cytotoxicity. For ionic copper, free copper concentrations in vivo are extremely buffered, so simple CuSO4 or CuCl2 in-vitro experiments do not map cleanly onto physiological free copper. For DSF/Cu and copper complexes, exposure relevance depends on complex formation, albumin/protein binding, tumor delivery, and copper transporter state.

Clinical evidence status: Copper biology is strongly supported mechanistically. Copper chelation has small human and phase II evidence, mainly as an anti-angiogenic or microenvironment strategy, but is not established standard oncology care. DSF/Cu has phase I/II and randomized clinical evidence in glioblastoma; the recurrent glioblastoma randomized trial did not show survival benefit and reported increased toxicity. CuNP/CuO-NP anticancer claims remain predominantly preclinical, with major translation constraints from oxidative, hepatic, renal, inflammatory, genotoxic, and mitochondrial toxicity signals.

Interpretation note: Copper biology and copper nanoparticles should not be treated as equivalent exposures. Ionic copper, nutritional copper, copper chelation, copper ionophores, copper complexes, CuNPs, CuO-NPs, and Cu2O-NPs differ in pharmacokinetics, intracellular copper delivery, redox behavior, biodistribution, and toxicity. Directional tags such as ROS↑, angiogenesis↑/↓, GSH↓, NRF2↑/↓, and chemosensitization should be interpreted according to exposure class.

Copper Cancer Mechanism Table

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Copper homeostasis and cuproptosis Intracellular Cu ↑; lipoylated TCA protein aggregation ↑; Fe-S proteins ↓; proteotoxic stress ↑; cuproptosis ↑ Normally buffered by CTR1, ATP7A/ATP7B, metallothioneins, chaperones, ceruloplasmin, and biliary excretion R, G Mitochondrial regulated cell death Core mechanism for copper-loading strategies and copper ionophores. Most relevant in tumors with high mitochondrial respiration and vulnerable copper handling.
2 Copper-dependent angiogenesis Angiogenic tone ↑; VEGF/HIF-1α-linked signaling ↑ (context-dependent); endothelial recruitment ↑ Physiologic angiogenesis and wound repair require copper-dependent processes G Tumor vascular support Supports copper chelation as an antiangiogenic strategy. Copper sufficiency and copper depletion should be tagged separately.
3 LOX and ECM remodeling LOX/LOXL activity ↑; collagen crosslinking ↑; invasion/metastatic niche support ↑ Connective-tissue maturation and repair require copper-dependent lysyl oxidase activity G Invasion and metastasis support Mechanistically important for stromal remodeling and metastasis rather than acute cancer-cell killing.
4 Copper chelation Available copper ↓; angiogenesis ↓; SOD1/LOX-dependent support ↓; metastatic niche support ↓ (context-dependent) Copper-dependent enzymes ↓ if depletion is excessive; deficiency risk ↑ G Microenvironment suppression Best represented as a separate therapeutic direction from copper supplementation or copper ionophore loading.
5 Disulfiram and copper ionophore stress Intracellular copper stress ↑; ROS ↑; proteasome stress ↑; ALDH/resistance pathways ↓ (model-dependent); apoptosis ↑ Toxicity ↑ possible; hepatic, neurologic, and drug-alcohol constraints are relevant R, G Experimental copper-loading therapy Preclinical signal is strong, but clinical results are mixed. Should not be generalized to dietary copper.
6 Mitochondrial ROS increase ROS ↑; mtROS ↑; mitochondrial membrane potential ↓; apoptosis ↑ Oxidative injury ↑ if copper buffering is exceeded P, R, G Redox-mediated cytotoxicity Most relevant for copper complexes, copper ionophores, and excess intracellular copper. Free Cu is highly buffered in vivo.
7 GSH and thiol redox buffering GSH ↓; GSH/GSSG ↓; oxidative vulnerability ↑; ferroptosis-like stress ↑ (context-dependent) GSH depletion can increase normal-tissue injury R, G Redox-buffer collapse Important for copper-loading and copper-complex strategies. Less applicable to normal dietary copper exposure.
8 NRF2 antioxidant response NRF2 ↓ in some copper-stress or DSF/Cu models; NRF2 ↑ as adaptive resistance in others NRF2 ↑ may protect against copper-associated oxidative stress R, G Adaptive stress response Direction is context-dependent. Use caution when assigning a single NRF2 direction to copper broadly.
9 SOD1 and copper-dependent enzymes SOD1 activity altered; copper-dependent redox enzyme support ↑ or ↓ depending on copper loading versus chelation Normal antioxidant defense, iron handling, connective tissue biology, and neurobiology depend on copper enzymes R, G Enzyme cofactor modulation Therapeutic leverage exists, but copper enzyme disruption has a narrow safety window.
10 Radiosensitization and chemosensitization ROS ↑; DNA damage ↑; TMZ/radiation response ↑ in selected models; apoptosis ↑ Normal-tissue sensitization risk ↑ if delivery is not tumor-selective R, G Adjunct sensitization Most relevant to DSF/Cu and copper complexes. Not established as a broad copper effect.
11 Clinical Translation Constraint Tumor response depends on copper transporter state, mitochondrial metabolism, GSH/NRF2 buffering, and copper-complex delivery Systemic copper is essential; excess copper and copper depletion can both cause toxicity G Exposure and safety constraint Dietary copper, copper salts, copper chelation, copper complexes, and DSF/Cu should be interpreted separately.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid redox interactions)
  • R: 30 min–3 hr (acute mitochondrial/proteotoxic stress signaling)
  • G: >3 hr (gene-regulatory adaptation and phenotype outcomes)

Copper Nanoparticles: CuNP / CuO-NP (tox + “anticancer” claims are mostly preclinical)

Copper Nanoparticle Cancer Mechanism Table

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Nanoparticle uptake and intracellular copper release CuNP/CuO-NP uptake ↑; lysosomal dissolution ↑; intracellular Cu ions ↑; cytotoxic stress ↑ Particle uptake can also occur in normal cells; macrophage, liver, kidney, lung, and endothelial exposure are major concerns R, G Particle-driven copper stress Core CuNP mechanism. Effects depend strongly on particle size, coating, oxidation state, dissolution rate, aggregation, and route of exposure.
2 Mitochondrial ROS increase ROS ↑; mtROS ↑; mitochondrial membrane potential ↓; ATP ↓; apoptosis ↑ Oxidative injury ↑; mitochondrial toxicity ↑ when exposure exceeds antioxidant capacity P, R, G Oxidative cytotoxicity Central anticancer mechanism but also the main normal-tissue toxicity concern. Tumor selectivity is not automatic.
3 GSH depletion and thiol-buffer collapse GSH ↓; GSH/GSSG ↓; lipid peroxidation ↑; oxidative vulnerability ↑ GSH depletion ↑; hepatic, renal, immune-cell, and pulmonary toxicity risk ↑ R, G Redox-buffer collapse Mechanistically important for CuO-NP and CuNP toxicity. Should be tagged as dose- and exposure-dependent.
4 DNA damage and genotoxicity Oxidative DNA damage ↑; strand breaks ↑; cell-cycle arrest ↑; apoptosis ↑ Genotoxicity risk ↑ in normal cells at toxic nanoparticle exposures R, G Genome damage Common downstream result of ROS and copper-ion release. Important safety flag.
5 Apoptosis and mitochondrial death signaling BAX/caspase signaling ↑; BCL-2 ↓; cytochrome-c release ↑; apoptosis ↑ Apoptosis ↑ possible in normal exposed tissues R, G Programmed cell death Frequently reported in cell studies, but not unique to cancer cells unless targeting or differential uptake is demonstrated.
6 Inflammatory signaling and NF-κB NF-κB and inflammatory mediators ↑ or ↓ depending on model and dose Inflammation ↑; cytokine release ↑; innate immune activation ↑ R, G Inflammatory stress For CuNPs, NF-κB activation often indicates toxic inflammatory response rather than selective anticancer benefit.
7 NRF2 antioxidant response NRF2/HO-1 ↑ as adaptive defense; NRF2 collapse or ↓ may occur at high toxic exposure NRF2 ↑ may be protective against oxidative nanoparticle injury R, G Stress adaptation Usually secondary to ROS. Direction depends on exposure severity and time point.
8 Lipid peroxidation and ferroptosis-like stress Lipid ROS ↑; membrane damage ↑; ferroptosis-like death ↑ (model-dependent) Lipid peroxidation ↑; membrane injury ↑ R, G Oxidative membrane injury Can overlap with ferroptosis biology but should not be called ferroptosis unless GPX4, iron dependence, lipid peroxide rescue, or ferroptosis inhibitors are tested.
9 Ca²⁺ and membrane injury Membrane damage ↑; intracellular Ca²⁺ dysregulation ↑; mitochondrial permeability stress ↑ Ca²⁺ dysregulation and membrane toxicity ↑ possible in normal cells P, R Membrane and mitochondrial destabilization Relevant when CuNP/CuO-NP exposure causes membrane disruption or mitochondrial permeability transition.
10 Angiogenesis modulation Angiogenesis ↓ in some CuNP/CuO-NP anticancer models through oxidative or endothelial toxicity; angiogenic copper biology may also be supported by released copper Endothelial toxicity ↑; wound repair interference ↑ possible G Vascular modulation Direction is formulation- and dose-dependent. Do not merge with dietary copper angiogenesis support.
11 Radiosensitization and chemosensitization ROS ↑; DNA damage ↑; chemo/radiation response ↑ in selected preclinical models Normal-tissue sensitization risk ↑ without tumor-selective delivery R, G Adjunct sensitization Preclinical concept. Requires targeting, biodistribution, and toxicity validation before clinical interpretation.
12 Clinical Translation Constraint Anticancer effects depend on tumor uptake, particle dissolution, coating, size, aggregation, and local Cu release Systemic toxicity, immune activation, liver/kidney deposition, genotoxicity, and poor tumor selectivity are major constraints G Nanomedicine delivery constraint Most CuNP/CuO-NP oncology evidence remains preclinical. Direct in-vitro cytotoxicity should be weighted lower than in-vivo targeted-delivery evidence.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid ROS/redox interactions at particle surfaces)
  • R: 30 min–3 hr (mitochondrial stress + inflammatory signaling)
  • G: >3 hr (genotoxicity, apoptosis, organ-level outcomes)
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
4564- AgNPs,  GoldNP,  Cu,  Chemo,  PDT  Cytotoxicity and targeted drug delivery of green synthesized metallic nanoparticles against oral Cancer: A review
- Review, Var, NA
ROS↑, DNAdam↑, TumCCA↑, eff↑, Apoptosis↑, eff↓, ChemoSen↑,
6183- Cu,    Copper(II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response
- in-vitro, Liver, HepG2
ROS↑, MAPK↑, ERK↑, AP-1↑,
6182- Cu,    Role of cuproptosis in digestive system tumors (Review)
- Review, Var, NA
Cupro↑, TumCG↓, Apoptosis↑, ROS↑, Ferroptosis↑, ETC↓, MMP↓, Ca+2↑, Fenton↑, lipid-P↑, MPT↑, ATP↓, Cyt‑c↑, Casp↑, angioG↑, TumCP↑, TumCMig↑, TumCI↑, TumMeta↑, DDS↑, eff↑,
6177- Cu,    Toxicity of copper oxide nanoparticles: a review study
- Review, Nor, NA
*ROS↑, *Inflam↑, *toxicity↑, lipid-P↑, GSH↓, MDA↑, *SOD↓, *Catalase↓,
6176- Cu,    Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells
- in-vitro, Liver, HepG2
ROS↑, P53↑, MMP↓, Bax:Bcl2↑, Apoptosis↑, *Bacteria↓, MDA↑, GSH↓, eff↓, Casp3↑,
6171- Cu,    Copper in the tumor microenvironment and tumor metastasis
- Review, Var, NA
*angioG↑, other↑, *ROS↑, CTR1↝, other↝, COX17↝, ATOX1↝,
1639- Cu,  HCAs,    Green synthesis of copper oxide nanoparticles using sinapic acid: an underpinning step towards antiangiogenic therapy for breast cancer
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
angioG↓, tumCV↓, Dose↓, ROS↑,
1604- Cu,    Targeting copper metabolism: a promising strategy for cancer treatment
- Review, NA, NA
eff↓, eff↓, ROS↑, eff↑,
1603- Cu,  BP,  SDT,    Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response
- in-vitro, BC, 4T1 - in-vivo, NA, NA
GSH↓, Fenton↑, ROS↑, NO↑, sonoS↑, eff↑, NO↑, *toxicity∅, eff?,
1601- Cu,    The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress
- in-vitro, CRC, NA
i-CRT↓, ICD↑, i-ATP↓, i-HMGB1↓, ER Stress↑, ROS↑, DCells↑, CD8+↑, IL12↑, IFN-γ↑, TGF-β↓,
1600- Cu,    Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis
- Review, NA, NA
ER Stress↑, ROS↑, AntiTum↑, GSH↓, Ferroptosis↑, selectivity↑, GSH/GSSG↓, *ROS∅, eff↑,
1599- Cu,    Copper in tumors and the use of copper-based compounds in cancer treatment
- Review, NA, NA
ROS↑, RadioS↑,
1569- Cu,    Copper Nanoparticles as Therapeutic Anticancer Agents
- Review, NA, NA
Dose∅, Dose∅, ROS↑,
1598- Cu,    Targeting copper in cancer therapy: 'Copper That Cancer'
- Review, NA, NA
eff↓, eff↑, Dose∅, eff↑, angioG↑, ROS↑,
1597- Cu,    Anticancer potency of copper(II) complexes of thiosemicarbazones
- Review, NA, NA
eff↑, ROS↑,
1596- Cu,  CDT,    Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review
- Review, NA, NA
TumCD↑, Apoptosis↓, ROS↑, angioG↑, Cupro↑, Paraptosis↑, eff↑, eff↓, selectivity↑, DNAdam↑, eff↑, eff↑, eff↑, eff↑, Fenton↑, H2O2↑, eff↑, eff↑, eff↑, RadioS↑, ChemoSen↑, eff↑, *toxicity↝, other↑, eff↑,
1570- Cu,    Development of copper nanoparticles and their prospective uses as antioxidants, antimicrobials, anticancer agents in the pharmaceutical sector
- Review, NA, NA
selectivity↑, antiOx↑, ROS↑, eff↑, GSH↓, lipid-P↑, Catalase↓, SOD↓, other↑,
1571- Cu,    Copper in cancer: From pathogenesis to therapy
- Review, NA, NA
*toxicity↝, ROS↑, lipid-P↓, HNE↑, MAPK↑, JNK↑, AP-1↑, Beclin-1↑, ATG7↑, TumAuto↑, Apoptosis↑, HO-1↑, NQO1↑, mt-ROS↑, Fenton↑,
1572- Cu,    Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy
- Review, NA, NA
eff↑, Fenton↑, ROS↑, eff↑, mtDam↑, BAX↑, Bcl-2↓, MMP↓, Cyt‑c↑, Casp3↑, ER Stress↑, CHOP↑, Apoptosis↑, selectivity↑, eff↑, Pyro↑, Paraptosis↑, Cupro↑, ChemoSen↑, eff↑,
1595- Cu,    The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy
- Review, NA, NA
eff↑, ROS↑, eff↓,
1602- Cu,    A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy†
- in-vitro, BC, MCF-7 - in-vitro, BC, 4T1 - in-vitro, Lung, A549 - in-vitro, Liver, HepG2
eff↑, GSH↓, H2O2↑, ROS↑, *BioAv↑, selectivity↑, TumCCA↑, Apoptosis↑, Fenton↑, *toxicity?,
5012- DSF,  Cu,    Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems
ROS↑, ALDH↓, TumCP↓, CSCs↓, angioG↓, TumMeta↓, DNAdam↑, Proteasome↓, SOD1↓, GSR↓, ox-GSSG↑, GSH/GSSG↓, MMP↓, Akt↓, cycD1/CCND1↓, NF-kB↓, CSCs↓, MAPK↓, angioG↓, DrugR↓, EMT↓, Vim↓, BioAv↑, eff↑,
5009- DSF,  Cu,    Activation of Oxidative Stress and Down-Regulation of Nuclear Factor Erythroid 2-Related Factor May Be Responsible for Disulfiram/Copper Complex Induced Apoptosis in Lymphoid Malignancy Cell Lines
- vitro+vivo, lymphoma, NA
AntiTum↑, ROS↑, JNK↑, NRF2↓, eff↓, TumCD↑,
5006- DSF,  Cu,    Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition
- vitro+vivo, lymphoma, NA
TumCD↑, TumCP↑, Apoptosis↑, NRF2↓, ROS↑, p‑JNK↑, p65↓, eff↓, NF-kB↓,
4916- DSF,  Cu,    The immunomodulatory function and antitumor effect of disulfiram: paving the way for novel cancer therapeutics
- Review, Var, NA
TumCP↓, TumCMig↓, TumCI↓, eff↑, Imm↑, ROS↑, NF-kB↓, chemoP↑, JNK↑, FOXO↑, Myc↑, TumCCA↑, Apoptosis↑, RadioS↑, PD-L1↑, eff↑, CSCs↓, Dose↝, Half-Life↑,
4915- DSF,  Cu,    Disulfiram: A novel repurposed drug for cancer therapy
- Review, Var, NA
ROS↑, TumCD↑, NF-kB↓, CSCs↓, ChemoSen↑, RadioS↑, eff↑, selectivity↑, Proteasome?,
1764- PG,  Cu,    DNA strand break induction and enhanced cytotoxicity of propyl gallate in the presence of copper(II)
- in-vitro, Nor, GM05757
*DNAdam↑, *ROS↑, *Dose∅, *DNAdam∅,
629- VitC,  Cu,  Fe,    The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer
- in-vitro, NA, NA
ROS↑, DNAdam↑, NAD↓,

Showing Research Papers: 1 to 28 of 28

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 28

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↓, 1,   Fenton↑, 6,   Ferroptosis↑, 2,   GSH↓, 6,   GSH/GSSG↓, 2,   GSR↓, 1,   ox-GSSG↑, 1,   H2O2↑, 2,   HNE↑, 1,   HO-1↑, 1,   ICD↑, 1,   lipid-P↓, 1,   lipid-P↑, 3,   MDA↑, 2,   NQO1↑, 1,   NRF2↓, 2,   ROS↑, 25,   mt-ROS↑, 1,   SOD↓, 1,   SOD1↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   i-ATP↓, 1,   COX17↝, 1,   ETC↓, 1,   MMP↓, 4,   MPT↑, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ATG7↑, 1,   NAD↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 8,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp↑, 1,   Casp3↑, 2,   Cupro↑, 3,   Cyt‑c↑, 2,   Ferroptosis↑, 2,   JNK↑, 3,   p‑JNK↑, 1,   MAPK↓, 1,   MAPK↑, 2,   Myc↑, 1,   Paraptosis↑, 2,   Proteasome?, 1,   Proteasome↓, 1,   Pyro↑, 1,   TumCD↑, 4,  

Transcription & Epigenetics ⓘ

other↑, 3,   other↝, 1,   sonoS↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   i-CRT↓, 1,   ER Stress↑, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CSCs↓, 4,   EMT↓, 1,   ERK↑, 1,   FOXO↑, 1,   TumCG↓, 1,  

Migration ⓘ

AP-1↑, 2,   ATOX1↝, 1,   Ca+2↑, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCI↑, 1,   TumCMig↓, 1,   TumCMig↑, 1,   TumCP↓, 2,   TumCP↑, 2,   TumMeta↓, 1,   TumMeta↑, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   angioG↑, 3,   NO↑, 2,  

Barriers & Transport ⓘ

CTR1↝, 1,  

Immune & Inflammatory Signaling ⓘ

DCells↑, 1,   i-HMGB1↓, 1,   IFN-γ↑, 1,   IL12↑, 1,   Imm↑, 1,   NF-kB↓, 4,   p65↓, 1,   PD-L1↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 4,   DDS↑, 1,   Dose↓, 1,   Dose↝, 1,   Dose∅, 3,   DrugR↓, 1,   eff?, 1,   eff↓, 9,   eff↑, 29,   Half-Life↑, 1,   RadioS↑, 4,   selectivity↑, 6,  

Clinical Biomarkers ⓘ

Myc↑, 1,   PD-L1↑, 1,  

Functional Outcomes ⓘ

AntiTum↑, 2,   chemoP↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 113

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   ROS↑, 3,   ROS∅, 1,   SOD↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNAdam∅, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   Dose∅, 1,  

Functional Outcomes ⓘ

toxicity?, 1,   toxicity↑, 1,   toxicity↝, 2,   toxicity∅, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 15

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
28 Copper and Cu NanoParticles
5 Disulfiram
1 Silver-NanoParticles
1 Gold NanoParticles
1 Chemotherapy
1 Photodynamic Therapy
1 Hydroxycinnamic-acid
1 Black phosphorus
1 SonoDynamic Therapy UltraSound
1 chemodynamic therapy
1 Propyl gallate
1 Vitamin C (Ascorbic Acid)
1 Iron
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#:64  Target#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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