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 0Antioxidant
ROS">Rosmarinic acid 0Antioxidant
ROS">Citrate 00Neutral


Scientific Papers found: Click to Expand⟱
3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF7
ChemoSen↑, PI3K↓, Akt↓, ATP↓, GlucoseCon↓, ROS↑, PKM2↓, Glycolysis↓, CSCs↓, IGF-1R↓, Furin↓, RadioS↑,
3437- ALA,    Revisiting the molecular mechanisms of Alpha Lipoic Acid (ALA) actions on metabolism
- Review, Var, NA
*IronCh↑, *antiOx↑, *ROS↓, *GSH↑, *NF-kB↓, *AMPK⇅, *FAO↑, *GlucoseCon↑, *PI3K↑, *Akt?,
3438- ALA,    The Potent Antioxidant Alpha Lipoic Acid
- Review, NA, NA - Review, AD, NA
*antiOx↑, *cardioP↑, *cognitive↑, *AntiAge↑, *Inflam↓, *AntiCan↑, *neuroP↑, *IronCh↑, *ROS↑, *Weight↓, *Ach↑, *ROS↓, *GSH↑, *lipid-P↓, *memory↑, *NRF2↑, *ChAT↑, *GlucoseCon↑, *Acetyl-CoA↑,
3439- ALA,    The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles
- in-vitro, NA, NA
*ROS↓, *TAC↑, *eff↑, *SOD↑, *GPx↑, *Catalase↑, *GlucoseCon↑, *antiOx↑,
3440- ALA,    Protective effects of alpha lipoic acid (ALA) are mediated by hormetic mechanisms
- Review, AD, NA
*ROS↓, *neuroP↑, *Aβ↓, *cardioP?,
3442- ALA,    α‑lipoic acid modulates prostate cancer cell growth and bone cell differentiation
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B - in-vitro, Nor, 3T3
tumCV↓, TumCMig↓, TumCI↓, ROS↑, Hif1a↑, JNK↑, Casp↑, TumCCA↑, Apoptosis↑, selectivity↑,
3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *IronCh↑, *cognitive↑, *cardioP↓, AntiCan↑, *neuroP↑, *Inflam↓, *BioAv↓, *AntiAge↑, *Half-Life↓, *BioAv↝, other↝, EGFR↓, Akt↓, ROS↓, TumCCA↑, p27↑, PDH↑, Glycolysis↓, ROS↑, *eff↑, *memory↑, *motorD↑, *GutMicro↑,
3454- ALA,    Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness
- in-vitro, BC, MCF7 - in-vitro, BC, MDA-MB-231
TumCG↑, Glycolysis↓, ROS↑, CSCs↓, selectivity↑, LC3B-II↑, MMP↓, mitResp↓, ATP↓, OCR↓, NAD↓, p‑AMPK↑, GlucoseCon↓, lactateProd↓, HK2↓, PFK↓, LDHA↓, eff↓, mTOR↓, ECAR↓, ALDH↓, CD44↓, CD24↓,
3451- ALA,    Alpha-lipoic acid ameliorates H2O2-induced human vein endothelial cells injury via suppression of inflammation and oxidative stress
- in-vitro, Nor, HUVECs
*LDH↓, *NOX4↓, *NF-kB↓, *iNOS↓, *VCAM-1↓, *ICAM-1↓, *ROS↓, *cardioP↑,
3448- ALA,    Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line
*Inflam↓, *ROS↓, *GSH↑, *GPx↑, *Casp3↓, *Casp9↓, *MMP↑,
3447- ALA,    Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells
- in-vitro, AD, SH-SY5Y
*ATP↑, *MMP↑, *ROS↓, *GlucoseCon↑, *GSH↑, *neuroP↑, *cognitive↑, *Ach↑, *Inflam↓, *Aβ↓, OXPHOS↓,
3446- ALA,  CUR,    The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression
- in-vivo, Nor, NA
*hepatoP↑, *α-SMA↓, *COL3A1↓, *ROS↓, *GSH↑, *ALAT↓, *AST↓, *ALP↓, *MDA↓,
3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, *IronCh↑, *GSH↑, *antiOx↑, *NRF2↑, *MMP9↓, *VCAM-1↓, *NF-kB↓, *cognitive↑, *Inflam↓, *BioAv↝, *BioAv↝, *BBB↑, *H2O2∅, *neuroP↑, *PKCδ↑, *ERK↑, *MAPK↑, *PI3K↑, *Akt↑, *PTEN↓, *AMPK↑, *GLUT4↑, *GlucoseCon↑, *BP↝, *eff↑, *ICAM-1↓, *VCAM-1↓, *Dose↝,
3541- ALA,    Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
- Review, Var, NA
*antiOx↑, *IronCh↑, *GSH↑, *BBB↑, Apoptosis↑, MMP↓, ROS↑, lipid-P↑, PARP1↑, Casp3↑, Casp9↑, *NRF2↑, *GSH↑, *ROS↓, RenoP↑, ChemoSen↑, *BG↓,
3543- ALA,    The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease
- Study, AD, NA
*cognitive↑, *antiOx↑, *Inflam↓, *neuroP↑, *Ach↑, *ROS↓, *GlucoseCon↑, *lipid-P↓, *GSH↑, *Acetyl-CoA↑,
3550- ALA,    Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?
- Review, AD, NA
*antiOx↑, *Inflam↓, *PGE2↓, *COX2↓, *iNOS↓, *TNF-α↓, *IL1β↓, *IL6↓, *BioAv↓, *Ach↑, *ROS↓, *cognitive↑, *neuroP↑, *BBB↑, *Half-Life↓, *BioAv↑, *Casp3↓, *Casp9↓, *ChAT↑, *cognitive↑, *eff↑, *cAMP↑, *IL2↓, *INF-γ↓, *TNF-α↓, *SIRT1↑, *SOD↑, *GPx↑, *MDA↓, *NRF2↑,
3549- ALA,    Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
- Review, AD, NA
*Inflam↓, *other↝, *other↝, *neuroP↑, *BioAv↝, *adiP↑, *BBB↑, *Casp6↓, *Casp9↓, *TNF-α↓, *IL6↓, *IL1β↓, *ROS↓, *NO↓, *iNOS↓, *COX2↓, *JNK↓, *p‑NF-kB↓, *Aβ↓, *BP↓, *memory↑, *cAMP↑, *ERK↑, *Akt↑, cognitive?,
3548- ALA,    How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease
- Review, AD, NA
*BBB↑, *other↑, *other↑, *DHA↑, *neuroP↑, *ROS↓, *other?,
3546- ALA,    Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study
- Study, AD, NA
*antiOx↑, *ROS↓, *cognitive∅, *lipid-P↓, *memory↑, *ChAT↑, *Acetyl-CoA↑, *Aβ↓, *BioAv↑, *BBB↑, *toxicity∅,
3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, *Inflam↓, *VCAM-1↓, *5HT↑, *memory↑, *BioAv↝, *Half-Life↓, *NF-kB↓, *antiOx↑, *IronCh↑, *ROS↓, *ATP↑, *ChAT↑, *Ach↑, *cognitive↑, *lipid-P↓, *VitC↑, *VitE↑, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *Aβ↓,
3544- ALA,    Alpha lipoic acid for dementia
- Review, AD, NA
*antiOx↑, *BBB↑, *VitC↑, *VitE↑, *GSH↑, *IronCh↑, *neuroP↑, *NO↓, *cognitive↑, *AntiAge↑, *memory↑, *ROS↓,
3859- ALC,    Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment
- Review, AD, NA
*ROS↓, *ADAM10↑,
1253- aLinA,    The Antitumor Effects of α-Linolenic Acid
- Review, NA, NA
PPARγ↑, COX2↓, E6↓, E7↓, P53↑, p‑ERK↓, p38↓, lipid-P↑, ROS⇅, MPT↑, MMP↓, Cyt‑c↑, Casp↑, iNOS↓, NO↓, Casp3↑, Bcl-2↓, Hif1a↓, FASN↓, CRP↓, IL6↓, IL1β↓, IFN-γ↓, TNF-α↓, Twist↓, VEGF↓, MMP2↓, MMP9↓,
6601- Anamu,    Petiveria alliacea Reduces Tumor Burden and Metastasis and Regulates the Peripheral Immune Response in a Murine Myeloid Leukemia Model
- in-vitro, AML, NA
AntiTum↑, GlucoseCon↓, ROS↑, TumCP↓, eff↓, Glycolysis↓,
6599- Anamu,    Potential behavioral and pro-oxidant effects of Petiveria alliacea L. extract in adult rats
*Dose↝, *motorD↑, *memory↑, *ROS↑,
1352- And,    Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy
- in-vitro, AML, K562
Apoptosis↑, ROS↑, HSP90↓,
1354- And,    Andrographolide induces protective autophagy and targeting DJ-1 triggers reactive oxygen species-induced cell death in pancreatic cancer
- in-vitro, PC, NA - in-vivo, PC, NA
Apoptosis↑, DJ-1↓, ROS↑, TumAuto↑, TumCCA↑, TumCP↓, TumW↓, eff↓,
1351- And,  MEL,    Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids
- in-vitro, CRC, T84 - in-vitro, CRC, COLO205 - in-vitro, CRC, HT-29 - in-vitro, CRC, DLD1
eff↑, Ki-67↓, Casp3↑, ER Stress↑, ROS↑, BAX↑, XBP-1↑, CHOP↑, eff↑,
1350- And,  Cisplatin,    Synergistic antitumor effect of Andrographolide and cisplatin through ROS-mediated ER stress and STAT3 inhibition in colon cancer
- in-vitro, Colon, NA
ChemoSen↑, ER Stress↑, STAT3↓, ROS↑,
1349- And,    Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction
- in-vitro, Lung, H460 - in-vitro, Lung, H1650
TumCG↓, TumMeta↓, Ferroptosis↑, ROS↑, MDA↑, Iron↑, GSH↓, GPx4↓, xCT↓, MMP↓, ATP↓,
1347- And,    Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide
- in-vitro, Nor, NA
*ROS↓,
1348- And,    Andrographolide Inhibits ER-Positive Breast Cancer Growth and Enhances Fulvestrant Efficacy via ROS-FOXM1-ER-α Axis
- in-vitro, BC, MCF7 - in-vitro, BC, T47D - in-vivo, NA, NA
ERα/ESR1↓, TumCG↓, ROS↑, FOXM1↓, eff↑,
931- And,    Effect of Andrographis Paniculata Aqueous Extract on Hyperammonemia Induced Alteration of Oxidative and Nitrosative Stress Factors in the Liver, Spleen and Kidney of Rats
- in-vivo, NA, NA
*SOD↝, *Catalase↝, *ROS↓, *MDA↓, *NO↓,
1093- And,    Andrographolide attenuates epithelial‐mesenchymal transition induced by TGF‐β1 in alveolar epithelial cells
- in-vitro, Lung, A549
TGF-β↓, TumCMig↓, MMP2↓, MMP9↓, ECM/TCF↓, p‑SMAD2↓, p‑SMAD3↓, SMAD4↓, p‑ERK↓, ROS↓, NOX4↓, SOD2↑, SIRT1↑, FOXO3↑,
6396- ANE,  FEO,    Anethole Inhibits the Proliferation of Human Prostate Cancer Cells via Induction of Cell Cycle Arrest and Apoptosis
- in-vitro, Pca, PC3
TumCP↓, TumCG↓, TumCMig↓, CSCs↓, ROS↑, MPT↑, Casp3↑, Casp9↑, DNAdam↑, cl‑PARP↑, Bax:Bcl2↑, TumCCA↑, cycD1/CCND1↓, CDK4↓, cMyc↓, P21↑, p27↑, NF-kB↓, eff↑,
6397- ANE,  Cisplatin,    Synergistic Effect of Anethole and Platinum Drug Cisplatin against Oral Cancer Cell Growth and Migration by Inhibiting MAPKase, Beta-Catenin, and NF-κB Pathways
- in-vitro, SCC, Ca9-22
AntiCan↑, ChemoSen↑, TumCP↓, MMP↓, ROS↑, MAPK↓, β-catenin/ZEB1↓, NF-kB↓, EMT↓, Casp↑,
6398- ANE,    trans-Anethole Abrogates Cell Proliferation and Induces Apoptosis through the Mitochondrial-Mediated Pathway in Human Osteosarcoma Cells
- in-vitro, OS, MG63
*Inflam↓, *AntiTum↑, TumCCA↓, ROS↑, MMP↓, Casp3↑, Casp9↑, P53↑, Bcl-xL↓, MPT↑,
6400- ANE,  FEO,    A comprehensive review of the neurological effects of anethole
- Review, AD, NA
*neuroP↑, *antiOx↓, *ROS↓, *Inflam↓, *TNF-α↓, *IL1β↓, *IL6↓, *motorD↑, *MAOA↓, *memory↑, *AChE↑, *PI3K↑, *Akt↑, *mTOR↑,
6404- ANE,    Anethole induces apoptotic cell death accompanied by reactive oxygen species production and DNA fragmentation in Aspergillus fumigatus and Saccharomyces cerevisiae
- in-vitro, Var, NA
ROS↑, DNAdam↑, TumCD↑,
6406- ANE,    Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways
- in-vitro, Oral, Ca9-22
TumCP↓, Apoptosis↑, TumAuto↑, ROS↓, GSH↑, cycD1/CCND1↓, P21↑, P53↑, EMT↓, Casp3↑, PARP1↑, TumMeta↓, MMPs↓, TIMP1↑,
4759- antiOx,  Chemo,    Potential Contributions of Antioxidants to Cancer Therapy: Immunomodulation and Radiosensitization
- Review, Var, NA
TumCD↑, TumCG↓, ROS⇅, eff↑, RadioS↑, TumCG↓, OS↑, toxicity∅, toxicity↑,
4279- Api,    The Beneficial Role of Apigenin against Cognitive and Neurobehavioural Dysfunction: A Systematic Review of Preclinical Investigations
- Review, NA, NA
*antiOx↑, *Inflam↓, *BBB↑, *5HT↑, *CREB↑, *BDNF↑, *memory↑, *motorD↑, *Mood↑, *cognitive↑, *ROS↓,
4280- Api,    Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms
- Review, AD, NA - Review, Park, NA
*neuroP↑, *antiOx↑, *ROS↓, *Inflam↓, *TNF-α↓, *IL1β↓, *PI3K↑, *Akt↑, *BBB↑, *NRF2↑, *SOD↑, *GPx↑, *MAPK↓, *Catalase↑, *HO-1↑, *COX2↓, *PGE2↓, *PPARγ↑, *TLR4↓, *GSK‐3β↓, *Aβ↓, *NLRP3↓, *BDNF↑, *TrkB↑, *GABA↑, *AChE↓, *Ach↑, *5HT↑, *cognitive↑, *MAOA↓,
586- Api,  5-FU,    5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)-mediated apoptosis in hepatocellular carcinoma
- in-vivo, HCC, NA
ROS↑, MMP↓, Bcl-2↓, Casp3↑, PARP↑,
313- Api,    Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells
- in-vitro, Thyroid, BCPAP
LC3s↝, p62↓, ROS↑, TumCCA↑, CDC25↓, TumAuto↑, Beclin-1↑, AVOs↑, DNAdam↑,
206- Api,    Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress
- in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, Melanoma, A375 - in-vitro, Lung, H2030 - in-vitro, CRC, SW480
Glycolysis↓, lactateProd↓, PGK1↓, ALDOA↓, GLUT1↓, ENO1↓, ATP↓, Casp9↑, Casp3↑, cl‑PARP↑, PI3K/Akt↓, HK1↓, HK2↓, ROS↑, Apoptosis↑, eff↓, NADPH↓, PPP↓,
171- Api,    Apigenin in cancer therapy: anti-cancer effects and mechanisms of action
- Review, Var, NA
PI3K/Akt↓, NF-kB↓, CK2↓, FOXO↓, MAPK↝, ERK↓, p‑JAK↓, Wnt/(β-catenin)↓, ROS↑, CDC25↓, p‑STAT↓, DNAdam↑,
416- Api,    In Vitro and In Vivo Anti-tumoral Effects of the Flavonoid Apigenin in Malignant Mesothelioma
- vitro+vivo, NA, NA
Bax:Bcl2↑, P53↑, ROS↑, Casp9↑, Casp8↑, cl‑PARP1↑, p‑ERK⇅, p‑JNK↓, p‑p38↑, p‑Akt↓, cJun↓, NF-kB↓, EGFR↓, TumCCA↑,
2631- Api,    Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells
- in-vivo, GC, NA - in-vitro, GC, AGS
ER Stress↑, Hif1a↓, EZH2↓, HDAC↓, TumAuto↑, p‑mTOR↓, AMPKα↑, GRP78/BiP↑, ROS↑, MMP↓, Ca+2↑, ATF4↑, CHOP↑,
2632- Api,    Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress
- in-vitro, EC, NA
TumCP↓, TumCCA↑, Apoptosis↑, Bcl-2↓, BAX↑, Bak↑, Casp↑, ER Stress↑, Ca+2↑, ATF4↑, CHOP↑, ROS↑, MMP↓, TumCMig↓, TumCI↓, eff↑, P53↑, P21↑, Cyt‑c↑, Casp9↑, Casp3↑, Bcl-xL↓,

Showing Research Papers: 201 to 250 of 2389
Prev Page 5 of 48 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2389

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1)

DJ-1↓, 1,   Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 1,   GSH↑, 1,   HK1↓, 1,   Iron↑, 1,   lipid-P↑, 2,   MDA↑, 1,   NOX4↓, 1,   OXPHOS↓, 1,   ROS↓, 3,   ROS↑, 23,   ROS⇅, 2,   SOD2↑, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics(tgid=3)

ATP↓, 4,   CDC25↓, 2,   mitResp↓, 1,   MMP↓, 9,   MPT↑, 3,   OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4)

ALDOA↓, 1,   p‑AMPK↑, 1,   cMyc↓, 1,   ECAR↓, 1,   ENO1↓, 1,   FASN↓, 1,   GlucoseCon↓, 3,   Glycolysis↓, 5,   HK2↓, 2,   lactateProd↓, 2,   LDHA↓, 1,   NAD↓, 1,   NADPH↓, 1,   PDH↑, 1,   PFK↓, 1,   PGK1↓, 1,   PI3K/Akt↓, 2,   PKM2↓, 1,   PPARγ↑, 1,   PPP↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5)

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 7,   Bak↑, 1,   BAX↑, 2,   Bax:Bcl2↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 2,   Casp↑, 4,   Casp3↑, 9,   Casp8↑, 1,   Casp9↑, 6,   CK2↓, 1,   Cyt‑c↑, 2,   Ferroptosis↑, 1,   iNOS↓, 1,   JNK↑, 1,   p‑JNK↓, 1,   MAPK↓, 1,   MAPK↝, 1,   p27↑, 2,   p38↓, 1,   p‑p38↑, 1,   TumCD↑, 2,  

Kinase & Signal Transduction(tgid=6)

AMPKα↑, 1,  

Transcription & Epigenetics(tgid=7)

cJun↓, 1,   EZH2↓, 1,   other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8)

CHOP↑, 3,   ER Stress↑, 4,   GRP78/BiP↑, 1,   HSP90↓, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes(tgid=9)

AVOs↑, 1,   Beclin-1↑, 1,   LC3B-II↑, 1,   LC3s↝, 1,   p62↓, 1,   TumAuto↑, 4,  

DNA Damage & Repair(tgid=10)

DNAdam↑, 4,   P53↑, 5,   PARP↑, 1,   cl‑PARP↑, 2,   PARP1↑, 2,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence(tgid=11)

CDK4↓, 1,   cycD1/CCND1↓, 2,   P21↑, 3,   TumCCA↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State(tgid=12)

ALDH↓, 1,   CD24↓, 1,   CD44↓, 1,   CSCs↓, 3,   EMT↓, 2,   ERK↓, 1,   p‑ERK↓, 2,   p‑ERK⇅, 1,   FOXM1↓, 1,   FOXO↓, 1,   FOXO3↑, 1,   HDAC↓, 1,   IGF-1R↓, 1,   mTOR↓, 1,   p‑mTOR↓, 1,   PI3K↓, 1,   p‑STAT↓, 1,   STAT3↓, 1,   TumCG↓, 5,   TumCG↑, 1,   Wnt/(β-catenin)↓, 1,  

Migration(tgid=13)

Ca+2↑, 2,   Furin↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP9↓, 2,   MMPs↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   SMAD4↓, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TumCI↓, 2,   TumCMig↓, 4,   TumCP↓, 6,   TumMeta↓, 2,   Twist↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14)

ATF4↑, 2,   ECM/TCF↓, 1,   EGFR↓, 2,   Hif1a↓, 2,   Hif1a↑, 1,   NO↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15)

GLUT1↓, 1,  

Immune & Inflammatory Signaling(tgid=16)

COX2↓, 1,   CRP↓, 1,   IFN-γ↓, 1,   IL1β↓, 1,   IL6↓, 1,   p‑JAK↓, 1,   NF-kB↓, 4,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors(tgid=20)

ERα/ESR1↓, 1,  

Drug Metabolism & Resistance(tgid=21)

ChemoSen↑, 4,   eff↓, 4,   eff↑, 6,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers(tgid=22)

CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 2,   ERα/ESR1↓, 1,   EZH2↓, 1,   FOXM1↓, 1,   IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes(tgid=23)

AntiCan↑, 2,   AntiTum↑, 1,   cognitive?, 1,   OS↑, 1,   RenoP↑, 1,   toxicity↑, 1,   toxicity∅, 1,   TumW↓, 1,  
Total Targets: 171

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1)

antiOx↓, 1,   antiOx↑, 13,   Catalase↑, 3,   Catalase↝, 1,   GPx↑, 5,   GSH↑, 11,   H2O2∅, 1,   HO-1↑, 1,   lipid-P↓, 4,   MDA↓, 3,   NOX4↓, 1,   NRF2↑, 5,   ROS↓, 24,   ROS↑, 2,   SOD↑, 4,   SOD↝, 1,   TAC↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology(tgid=2)

IronCh↑, 7,  

Mitochondria & Bioenergetics(tgid=3)

ATP↑, 2,   MMP↑, 2,  

Core Metabolism/Glycolysis(tgid=4)

Acetyl-CoA↑, 3,   adiP↑, 1,   ALAT↓, 1,   AMPK↑, 1,   AMPK⇅, 1,   cAMP↑, 2,   CREB↑, 1,   DHA↑, 1,   FAO↑, 1,   GlucoseCon↑, 6,   LDH↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death(tgid=5)

Akt?, 1,   Akt↑, 4,   Casp3↓, 2,   Casp6↓, 1,   Casp9↓, 3,   iNOS↓, 3,   JNK↓, 1,   MAPK↓, 1,   MAPK↑, 1,  

Transcription & Epigenetics(tgid=7)

Ach↑, 6,   other?, 1,   other↑, 2,   other↝, 2,  

Proliferation, Differentiation & Cell State(tgid=12)

ERK↑, 2,   GSK‐3β↓, 1,   mTOR↑, 1,   PI3K↑, 4,   PTEN↓, 1,  

Migration(tgid=13)

COL3A1↓, 1,   MMP9↓, 1,   PKCδ↑, 1,   VCAM-1↓, 4,   α-SMA↓, 1,  

Angiogenesis & Vasculature(tgid=14)

NO↓, 3,  

Barriers & Transport(tgid=15)

BBB↑, 9,   GLUT4↑, 1,  

Immune & Inflammatory Signaling(tgid=16)

COX2↓, 3,   ICAM-1↓, 2,   IL1β↓, 4,   IL2↓, 1,   IL6↓, 3,   INF-γ↓, 1,   Inflam↓, 13,   NF-kB↓, 4,   p‑NF-kB↓, 1,   PGE2↓, 2,   TLR4↓, 1,   TNF-α↓, 5,  

Synaptic & Neurotransmission(tgid=18)

5HT↑, 3,   AChE↓, 1,   AChE↑, 1,   ADAM10↑, 1,   BDNF↑, 2,   ChAT↑, 4,   GABA↑, 1,   MAOA↓, 2,   TrkB↑, 1,  

Protein Aggregation(tgid=19)

Aβ↓, 6,   NLRP3↓, 1,  

Drug Metabolism & Resistance(tgid=21)

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 5,   Dose↝, 2,   eff↑, 4,   Half-Life↓, 3,  

Clinical Biomarkers(tgid=22)

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BG↓, 1,   BP↓, 1,   BP↝, 1,   GutMicro↑, 1,   IL6↓, 3,   LDH↓, 1,  

Functional Outcomes(tgid=23)

AntiAge↑, 3,   AntiCan↑, 1,   AntiTum↑, 1,   cardioP?, 1,   cardioP↓, 1,   cardioP↑, 2,   cognitive↑, 11,   cognitive∅, 1,   hepatoP↑, 1,   memory↑, 9,   Mood↑, 1,   motorD↑, 4,   neuroP↑, 13,   toxicity∅, 1,   Weight↓, 1,  
Total Targets: 114

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
122 Silver-NanoParticles
99 Curcumin
94 Quercetin
88 Magnetic Fields
74 Thymoquinone
56 Resveratrol
55 Shikonin
54 Vitamin C (Ascorbic Acid)
50 Berberine
50 Sulforaphane (mainly Broccoli)
49 Radiotherapy/Radiation
47 Lycopene
45 EGCG (Epigallocatechin Gallate)
43 Baicalein
42 Alpha-Lipoic-Acid
40 Selenite (Sodium)
40 Ashwagandha(Withaferin A)
40 Piperlongumine
39 Selenium NanoParticles
38 Artemisinin
37 Betulinic acid
36 Hydrogen Gas
34 Rosmarinic acid
33 Capsaicin
32 Silymarin (Milk Thistle) silibinin
29 Propolis -bee glue
29 Fisetin
28 Copper and Cu NanoParticles
28 Apigenin (mainly Parsley)
27 Chemotherapy
27 Honokiol
26 Allicin (mainly Garlic)
25 doxorubicin
25 Phenethyl isothiocyanate
24 Luteolin
24 Magnetic Field Rotating
23 Chrysin
22 Cisplatin
22 Vitamin K2
21 Chlorogenic acid
21 Gambogic Acid
20 Coenzyme Q10
20 chitosan
20 Juglone
18 Boron
17 salinomycin
17 Parthenolide
16 Emodin
16 Urolithin
15 Ellagic acid
15 Eugenol
14 Photodynamic Therapy
14 Auranofin
14 Boswellia (frankincense)
14 Carnosic acid
14 Carvacrol
14 Selenium
14 Crocetin
14 Phenylbutyrate
13 Dichloroacetate
13 Dandelion Root
13 Pterostilbene
12 Melatonin
12 Caffeic acid
12 VitK3,menadione
11 5-fluorouracil
11 Astaxanthin
11 Cinnamon
11 Graviola
11 Piperine
10 Beta-Caryophyllene
10 α-Bisabolol / Chamomile oil
10 Ursolic acid
10 diet FMD Fasting Mimicking Diet
10 Ferulic acid
10 Plumbagin
10 Nimbolide
9 SonoDynamic Therapy UltraSound
9 Andrographis
9 D-limonene
9 Bacopa monnieri
9 borneol
9 Centella asiatica / Gotu kola → asiaticoside
9 Diclofenac
8 Hydroxycinnamic-acid
8 Disulfiram
8 Electrical Pulses
8 Sulfasalazine
8 Hyperthermia
8 Methylene blue
8 Moringa oleifera
8 Propyl gallate
7 3-bromopyruvate
7 Gemcitabine (Gemzar)
7 EMF
7 Gold NanoParticles
7 Metformin
7 immunotherapy
7 Berbamine
7 brusatol
7 Carnosine
7 Celastrol
7 diet Methionine-Restricted Diet
7 eicosapentaenoic acid
7 HydroxyTyrosol
6 2-DeoxyGlucose
6 Anethole/trans-Anethole
6 Docetaxel
6 Biochanin A
6 Butyrate
6 Chlorophyllin
6 Citric Acid
6 Carvone
6 Aflavin-3,3′-digallate
5 1,8-Cineole
5 Brucea javanica
5 Bromelain
5 erastin
5 Thymol-Thymus vulgaris
5 Chocolate
5 Cichoric acid / Chicoric acid
5 Spermidine
5 Huperzine A/Huperzia serrata
5 Date Fruit Extract
5 Docosahexaenoic Acid
5 Garcinol
5 HydroxyCitric Acid
5 Magnolol
5 nicotinamide adenine dinucleotide
5 Rutin
4 chemodynamic therapy
4 Zinc
4 Vitamin E
4 Cucurbitacin
4 diet Short Term Fasting
4 Geraniol
4 γ-linolenic acid (Borage Oil)
4 Linalool
4 Magnesium
4 Naringin
4 Taurine
3 5-Aminolevulinic acid
3 Anthocyanins
3 Glucose
3 temozolomide
3 Black phosphorus
3 Paclitaxel
3 Catechins
3 Choline
3 Dihydrocaffeic Acid
3 Oxygen, Hyperbaric
3 Shilajit/Fulvic Acid
3 Ginkgo biloba
3 Orlistat
3 MCToil
3 Methylsulfonylmethane
3 Mushroom Lion’s Mane
3 Oleuropein
3 α-Santalol/Sandalwood oil
3 Shankhpushpi
3 Terpinen-4-ol / Tea Tree Oil
3 Turmerones
3 Vitamin B1/Thiamine
2 5-Hydroxytryptophan
2 Astragalus
2 DTS(dibenzyl trisulphide) from Anamu
2 Fennel Oil/Foeniculum vulgare
2 Aromatherapy
2 Ascorbyl Palmitate
2 Atorvastatin
2 Aloe anthraquinones
2 beta-glucans
2 Baicalin
2 xanthohumol
2 Cannabidiol
2 beta-carotene(VitA)
2 Bufalin/Huachansu
2 Bruteridin(bergamot juice)
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Cat’s Claw
2 Carica papaya leaf extract
2 Calorie Restriction Mimetics
2 Galantamine
2 CUSP9
2 Folic Acid, Vit B9
2 Fenbendazole
2 Galloflavin
2 Potassium
2 Methyl Jasmonate
2 Methylglyoxal
2 Myricetin
2 Vitamin B3,Niacin
2 Niclosamide (Niclocide)
2 Pachymic acid
2 Sanguinarine
2 Psoralidin
2 Radio Frequency
2 Sesame seeds and Oil
2 Iron
2 Salvia miltiorrhiza
2 Vitamin D3
1 cetuximab
1 entinostat
1 Camptothecin
1 Resiquimod
1 Anzaroot, Astragalus fasciculifolius Bioss
1 Ajoene (compound of Garlic)
1 Acetyl-l-carnitine
1 alpha Linolenic acid
1 Anti-oxidants
1 Sorafenib (brand name Nexavar)
1 tamoxifen
1 almonertinib
1 epirubicin
1 Lapatinib
1 Ras-selective lethal 3
1 Celecoxib
1 methotrexate
1 Aspirin
1 Rivastigmine
1 methylseleninic acid
1 Cyclopamine
1 Cysteamine
1 Dichloroacetophenone(2,2-)
1 Deguelin
1 diet Fermented Foods
1 diet Ketogenic
1 diet Plant based
1 Lemongrass Extract/Citral
1 Echinacea
1 Cannabichromene
1 Exercise
1 Fucoidan
1 Gallic acid
1 verapamil
1 hydroxychloroquine
1 Ginseng
1 hydrogen sulfide
1 Rapamycin
1 Ivermectin
1 lambertianic acid
1 Myrrh
1 N-Acetyl-Cysteine
1 No Product/Mechanism Only
1 Oleocanthal
1 sericin
1 Kaempferol
1 benzo(a)pyrene
1 Hyperoside
1 Perilla
1 Salvia officinalis
1 Oxaliplatin
1 Scoulerine
1 polyethylene glycol
1 acetaminophen
1 Formononetin
1 Silicic Acid
1 Squalene
1 Osimertinib
1 Adagrasib
1 Glutathione
1 statins
1 Safflower yellow
1 triptolide
1 Vitamin A, Retinoic Acid
1 Vitamin B12
1 Vitamin B2,Riboflavin
1 Vitamin B5,Pantothenic Acid
1 glucose deprivation
1 Transarterial Chemoembolization
1 probiotics
1 Zinc Oxide
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#:275  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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