ROS Cancer Research Results

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


PSA, Psoriasis: Click to Expand ⟱
Psoriasis is an autoimmune skin disease.
This section mainly deals with PsA which is psoriatic arthritis

PsA evidence based approach

Rank Approach Evidence Mechanism / Rationale Notes
1 Weight loss if overweight/obese Best direct evidence in PsA Reduces metabolic inflammation, adipokine burden, and joint inflammatory load; may improve treatment response. Highest-yield natural strategy when excess weight is present.
2 Regular exercise / physical activity Good supportive evidence Improves pain, stiffness, function, fatigue, muscle support, and cardiometabolic health. Strong adjunct for joint symptoms and overall health.
3 Mediterranean-style diet / antioxidant-rich whole-food diet Moderate evidence May reduce systemic inflammatory tone; provides polyphenols, fiber, unsaturated fats, and better metabolic support. Best antioxidant strategy is diet pattern rather than antioxidant pills.
4 Intermittent fasting / time-restricted eating Early limited evidence May improve inflammatory signaling and metabolic regulation; possible benefit for CRP, enthesitis, and disease activity. Promising but still exploratory.
5 Omega-3 (fish / fish oil) Mixed evidence Shifts eicosanoids toward less inflammatory profiles and may modestly reduce inflammatory tone. Reasonable adjunct, but not a top-tier PsA joint intervention.
6 Vitamin D Weak PsA-specific treatment evidence More relevant for deficiency correction, bone support, and immune modulation than for direct joint control. Most relevant when levels are low.

PsA pathways to modulate

Rank Pathway / Axis Why It Matters in PsA Joints Helpful Modulation Support Level
1 IL-23 → Th17/Tc17 → IL-17A/F Core inflammatory axis in psoriatic arthritis; active in synovium, enthesis, and related tissues. Reduce excessive IL-23 / IL-17 signaling and downstream cytokine/chemokine output. Very high
2 TNF-α / NF-κB inflammatory axis Major validated cytokine pathway driving inflammation, tissue injury, and amplification of disease activity. Reduce TNF / NF-κB-driven inflammatory signaling and matrix damage. Very high
3 JAK / STAT3 signaling Supports cytokine signaling relevant to synovial and entheseal inflammation. Dampen excessive JAK / STAT3 inflammatory activity. High
4 Myeloid / inflammasome amplification (IL-1β, IL-6, GM-CSF) Amplifies synovitis, pain, recruitment of inflammatory cells, and osteoclastogenic signaling. Reduce IL-1β, IL-6, and GM-CSF inflammatory amplification. High
5 RANKL / M-CSF / osteoclastogenesis Important for bone erosions and osteoclast-mediated damage. Reduce osteoclast differentiation and bone resorption pressure. High
6 DKK1 / Wnt / BMP bone-remodeling balance PsA involves both erosions and abnormal new bone formation. Rebalance remodeling rather than simply suppress all bone formation. Moderate to high
7 COX-2 / 5-LOX / eicosanoid signaling Contributes to inflammatory pain, swelling, and leukocyte recruitment. Reduce excess prostaglandin and leukotriene inflammatory tone. Moderate
8 KEAP1-NRF2 / oxidative stress-redox balance Oxidative imbalance may reinforce inflammatory signaling and tissue injury. Improve antioxidant defense and redox resilience. Moderate
9 Obesity / adipokine / metabolic inflammation axis Obesity is linked to worse disease activity and poorer response. Reduce metabolic inflammation and adverse adipokine signaling. Moderate
10 Gut microbiome / barrier / immune-metabolite axis Gut dysbiosis and barrier changes may influence systemic immune activation. Support gut barrier function and more favorable immune-metabolic signaling. Moderate

Natural products that might help PsA — mechanistic HTML table

Natural Product / Class Main PsA-Relevant Pathways Mechanistic Rationale Direct PsA Joint Evidence Practical Read
Omega-3 (EPA/DHA) IL-17-related signaling; TNF/NF-κB tone; eicosanoids / resolution pathways May shift lipid mediators toward less inflammatory profiles and reduce inflammatory signaling. Mixed / weak Most practical food/supplement adjunct, but not a strong standalone PsA joint therapy.
Curcumin / Turmeric NF-κB; JAK/STAT3; MAPK; IL-17 / IFN-γ; redox signaling Broad anti-inflammatory and signaling-modulating effects relevant to psoriatic disease biology. Very limited direct evidence Reasonable mechanistic adjunct; stronger biology than clinical PsA proof.
Boswellia / Boswellic acids 5-LOX; NF-κB; COX-2; leukotrienes Notable leukotriene / 5-LOX angle with broader anti-inflammatory effects. No strong direct PsA joint trials Plausible adjunct, especially for eicosanoid-driven inflammation.
Ginger NF-κB; COX / LOX; inflammatory pain pathways Anti-inflammatory and antioxidant actions with arthritis-relevant pathway effects. Indirect only Plausible low-to-moderate adjunct; evidence is not PsA-specific.
EGCG / Green tea catechins IL-17 / IL-23-related inflammation; oxidative stress; keratinocyte hyperproliferation Immune-regulatory and antioxidant effects; mainly supported in psoriasis/preclinical models. Mostly psoriasis / preclinical Interesting adjunct, but not proven for PsA joints.
Sulforaphane KEAP1-NRF2; oxidative stress; TH17-related inflammation; autoimmune signaling Strong redox / NRF2 rationale with anti-inflammatory effects in preclinical models. Preclinical / indirect Good mechanistic candidate for the NRF2-redox tier.
Quercetin NF-κB; PI3K/AKT/GLUT1; inflammatory cell signaling Multi-target anti-inflammatory effects with arthritis relevance. Weak direct PsA evidence Mechanistically attractive, clinically still speculative for PsA.
Resveratrol NF-κB; oxidative stress; inflammatory mediators; SIRT1/AMPK-linked effects May reduce inflammatory signaling and support metabolic/redox regulation. Very limited for PsA Interesting but not near the top for real-world PsA use.
Piperlongumine NLRP3 inflammasome; ROS-sensitive inflammatory signaling; FLS proliferation/migration; MMPs Research-stage anti-inflammatory candidate with RA/psoriasis-model relevance. Research-stage only Experimental; not a practical PsA supplement at present.
Shikonin JAK/STAT; TNF-driven synoviocyte signaling; macrophage polarization; psoriasis inflammation Biologically interesting for synovitis and immune-cell signaling. Research-stage only Experimental; mainly of mechanistic interest.


Scientific Papers found: Click to Expand⟱
2775- Bos,    The journey of boswellic acids from synthesis to pharmacological activities
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
ROS↑, ER Stress↑, TumCG↓, Apoptosis↑, Inflam↓, ChemoSen↑, Casp↑, ERK↓, cl‑PARP↑, AR↓, cycD1/CCND1↓, VEGFR2↓, CXCR4↓, radioP↑, NF-kB↓, VEGF↓, P21↑, Wnt↓, β-catenin/ZEB1↓, Cyt‑c↑, MMP2↓, MMP1↓, MMP9↓, PI3K↓, MAPK↓, JNK↑, *5LO↓, *NRF2↑, *HO-1↑, *MDA↓, *SOD↑, *hepatoP↑, *ALAT↓, *AST↓, *LDH↑, *CRP↓, *COX2↓, *GSH↑, *ROS↓, *Imm↑, *Dose↝, *eff↑, *neuroP↑, *cognitive↑, *IL6↓, *TNF-α↓,
2201- SK,    Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in mice
- in-vitro, PSA, HaCaT - in-vivo, NA, NA
*eff↑, *IL6↓, *IL17↓, *TNF-α↓, *lipid-P↑, *NRF2↓, *HO-1↝, *NCOA4↝, *GPx4↓, *Ferroptosis↓, *Inflam↓, *ROS↓, *Iron↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Casp↑, 1,   Cyt‑c↑, 1,   JNK↑, 1,   MAPK↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

MMP1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

CXCR4↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,  

Functional Outcomes ⓘ

radioP↑, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↓, 1,   GPx4↓, 1,   GSH↑, 1,   HO-1↑, 1,   HO-1↝, 1,   Iron↓, 1,   lipid-P↑, 1,   MDA↓, 1,   NRF2↓, 1,   NRF2↑, 1,   ROS↓, 2,   SOD↑, 1,  

Metal & Cofactor Biology ⓘ

NCOA4↝, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   LDH↑, 1,  

Cell Death ⓘ

Ferroptosis↓, 1,  

Migration ⓘ

5LO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL17↓, 1,   IL6↓, 2,   Imm↑, 1,   Inflam↓, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   CRP↓, 1,   IL6↓, 2,   LDH↑, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 34

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
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:74  Cells:%  prod#:%  Target#:275  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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