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


Scientific Papers found: Click to Expand⟱
4922- PEITC,    Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms
- Review, Var, NA
Risk↓, AntiCan↑, TumCP↓, TumMeta↓, ChemoSen↑, *BioAv↑, *other↝, *Dose↝, Dose↓, *BioAv↑, *Dose↝, *Half-Life↝, *toxicity↝, GSH↓, ROS↑, CYP1A1↑, CYP1A2↑, P450↓, CYP2E1↑, CYP3A4↓, CYP2A3/CYP2A6↓, *ROS↓, *GPx1↑, *SOD1↑, *SOD2↑, Akt↓, EGFR↓, HER2/EBBR2↓, P53↑, Telomerase↓, selectivity↑, MMP↓, Cyt‑c↑, Apoptosis↑, DR4↑, Fas↑, XIAP↓, survivin↓, TumAuto↑, Hif1a↓, angioG↓, MMPs↓, ERK↓, NF-kB↓, EMT↓, TumCI↓, TumCMig↓, Glycolysis↓, ATP↓, selectivity↑, *antiOx↑, Dose↝, other↝, OCR↓, GSH↓, ITGB1↓, ITGB6↓, ChemoSen↑,
4924- PEITC,    Nutri-PEITC Jelly Significantly Improves Progression-Free Survival and Quality of Life in Patients with Advanced Oral and Oropharyngeal Cancer: A Blinded Randomized Placebo-Controlled Trial
- Trial, Oral, NA
QoL↑, P53↑, OS↑, Cyt‑c↝, other↝, ROS↑, selectivity↑, P21↑, TumCCA↑, Dose↝, BioAv↑, Weight↑, chemoP↑,
4918- PEITC,    Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights
- Review, Var, NA
Apoptosis↑, TumCP↓, angioG↓, TumMeta↓, NF-kB↓, Akt↓, MAPK↓, *BioAv↓, ROS↑, lipid-P↑, AIF↑, Cyt‑c↑, DR4↑, DR5↑, TumCCA↑, JAK↓, STAT3↓, MMP2↓, MMP9↓, PKCδ↓, Hif1a↓, JNK↓, Mcl-1↓, COX2↓, MMP↓, Casp3↑, ChemoSen↑, *BioAv↓, Half-Life↓,
4944- PEITC,    Phenethyl isothiocyanate induces DNA damage-associated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations
- in-vitro, Oral, NA
TumCG↓, TumCCA↑, Apoptosis↑, ROS↑, NO↑, GSH↓, MMP↓, DNAdam↑, ATM↑, Chk2↑, P53↑, eff↓,
4925- PEITC,    PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells
- in-vitro, OS, NA
tumCV↓, TumCP↓, TumCCA↑, GSH↓, ROS↑, Ferroptosis↑, Apoptosis↑, TumAuto↑, MAPK↑, TumCG↓, Dose⇅,
4927- PEITC,    Targeting ferroptosis in osteosarcoma
- Review, OS, NA
AntiCan↑, BioAv↑, Ferroptosis↑, TfR1/CD71↑, Iron↑, ROS↑, MDA↑, lipid-P↑, GPx4↓,
4932- PEITC,    Pharmacokinetics and Pharmacodynamics of Phenethyl Isothiocyanate: Implications in Breast Cancer Prevention
- Review, BC, NA
TumCCA↑, ROS↑, GSH↓, ERα/ESR1↓, TumMeta↓, angioG↓,
4934- PEITC,    Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
GSH↓, ROS↑, chemoPv↑, Apoptosis↑, Casp9↑, Casp3↑, eff↓, TumCG↓, TumCCA↑, BAX↑, Nrf1↑, GSH↓, GSSG↓, GSH/GSSG↓,
4937- PEITC,    PEITC: Functional Compound for Primary and Tertiary Chemoprevention of Cancer
chemoPv↑, tumCV↓, GSH↓, ROS↑, *toxicity↝,
4940- PEITC,    Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G 0/G 1 Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death
- in-vitro, Oral, HSC3
TumCCA↑, Apoptosis↑, BAX↑, BID↑, Bcl-2↓, MMP↓, Cyt‑c↑, AIF↑, tumCV↓, ROS↑, Ca+2↑, CDC25↓, CDK6↓, cycD1/CCND1↓, CDK2↓, cycE/CCNE↓, P53↑, p27↑, P21↑, Casp9↑, Casp3↑, GRP78/BiP↑,
4941- PEITC,    PEITC: A resounding molecule averts metastasis in breast cancer cells in vitro by regulating PKCδ/Aurora A interplay
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
PKCδ↑, Apoptosis↓, selectivity↑, tumCV↓, p‑NRF2↑, cl‑PARP1↑, TumCMig↓, ROS↓, Hif1a↓,
4942- PEITC,    Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G(0)/G(1) Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death
- in-vitro, Oral, HSC3
chemoPv↑, TumCG↓, TumCCA↑, Apoptosis↑, BAX↑, BID↑, Bcl-2↓, MMP↓, Cyt‑c↑, AIF↑, ROS↑, Ca+2↑,
5183- PEITC,  Cisplatin,    Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells
- in-vitro, Cerv, HeLa - in-vitro, Nor, HaCaT
DNAdam↑, Apoptosis↑, ChemoSen↑, ROS↑, mt-ROS↑, Casp↑, Casp3↑, selectivity↑, TumCP↓, tumCV↓, eff↓,
5186- PEITC,    Phenethyl Isothiocyanate inhibits STAT3 activation in prostate cancer cells
- in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP
TumCP↓, TumCCA↑, STAT3↓, p‑JAK2↓, eff↓, TumCCA↑, AR↓, ROS↑,
5220- PG,  TMZ,    Propyl Gallate Exerts an Antimigration Effect on Temozolomide-Treated Malignant Glioma Cells through Inhibition of ROS and the NF- κ B Pathway
- in-vitro, GBM, U87MG
TumCMig↓, MMP2↓, MMP9↓, NF-kB↓, ROS↑, selectivity↑,
5218- PG,    Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy
- in-vitro, HCC, Hep3B
TumCP↓, Apoptosis↑, ROS↑, TumAuto↑, cl‑Casp3↑, cl‑PARP↑, BAX↑, BAD↑, Bcl-2↓, toxicity↓, hepatoP↑, GSH↓,
1767- PG,    Propyl gallate induces cell death in human pulmonary fibroblast through increasing reactive oxygen species levels and depleting glutathione
- in-vitro, Nor, NA
*ROS↑, *GSH↓, *SOD↓, *Catalase↓, eff↓,
1769- PG,    The Anti-Apoptotic Effects of Caspase Inhibitors in Propyl Gallate-Treated Lung Cancer Cells Are Related to Changes in Reactive Oxygen Species and Glutathione Levels
- in-vitro, Lung, Calu-6 - in-vitro, Lung, A549
TumCP↓, eff↑, ROS↑, GSH↓,
1772- PG,    Propyl gallate decreases the proliferation of Calu-6 and A549 lung cancer cells via affecting reactive oxygen species and glutathione levels
- in-vitro, Lung, Calu-6 - in-vitro, Lung, A549
ROS⇅, TumCP↓, GSH↓,
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∅,
1763- PG,    Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment
- Review, NA, NA
*antiOx↑, *ROS↓, *ROS↑,
1765- PG,    Enhanced cell death effects of MAP kinase inhibitors in propyl gallate-treated lung cancer cells are related to increased ROS levels and GSH depletion
- in-vitro, Lung, A549 - in-vitro, Lung, Calu-6
TumCD↑, MMP↓, ROS↑, GSH↓, Dose∅, eff↑,
1257- PI,    Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathways
- ex-vivo, LiverDam, NA
*Fibronectin↓, *α-SMA↓, *COL1↓, *COL3A1↓, *TGF-β↓, *EMT↓, *MMP2↓, *α-SMA↓, *Smad7↑, *E-cadherin↑, *Vim↓, *hepatoP↑, *antiOx↑, *GSH↑, *ROS↓,
1256- PI,    Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models
- in-vitro, adrenal, PHEO - in-vivo, NA, NA
Apoptosis↑, ROS↑, TumCMig↓, TumCI↓, EMT↓, angioG↓, Necroptosis↑, MAPK↑, ERK↑,
1254- PI,  VitC,    Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathway
- in-vivo, GC, NA
STAT3⇅, eff↑, ROS↑, Apoptosis↑,
5215- PI,    Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells
- in-vitro, CRC, NA
TumCCA↑, Apoptosis↑, ROS↑, eff↓, BioEnh↑,
5214- PI,    Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS production
- vitro+vivo, CRC, HCT116 - in-vitro, CRC, SW48 - in-vitro, CRC, SW-620
TumCP↓, TumAuto↑, Akt↓, mTOR↓, ROS↑,
5213- PI,    Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation
- in-vitro, Cerv, HeLa
Apoptosis↑, TumCG↓, ROS↑, MMP↓, DNAdam↑, Casp3↑, TumCCA↑, *Inflam↓, *antiOx↓, *hepatoP↑, ChemoSen↑, CSCs↓,
3587- PI,    Piperine: A review of its biological effects
- Review, Park, NA - Review, AD, NA
*hepatoP↑, *Inflam↓, *neuroP↑, *antiOx↑, *angioG↑, *cardioP↑, *BioAv↑, *P450↓, *eff↑, *BioAv↑, E-cadherin↓, ER(estro)↓, MMP2↓, MMP9↓, VEGF↓, cMyc↓, BAX↑, P53↑, TumCG↓, OS↑, *cognitive↑, *GSK‐3β↓, *GSH↑, *Casp3↓, *Casp9↓, *Cyt‑c↓, *lipid-P↓, *motorD↑, *AChE↓, *memory↑, *cardioP↑, *ROS↓, *PPARγ↑, *ALAT↓, *AST↓, *ALP↓, *AMPK↑, *5HT↑, *SIRT1↑, *eff↑,
3595- PI,    Black pepper and health claims: a comprehensive treatise
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *chemoP↑, TumCG↓, *cognitive↑, *MMPs↓, *PGE2↓, *AP-1↓, *5LO↓, *COX1↓, *other↑, *other↑, *other↑, *SOD↑, *Catalase↑, *GSTs↑, *GSR↑, *other↑, *Weight↓, *BioEnh↑, *BioAv↑, *eff↑, *CYP3A2↓, *neuroP↑, *BP↓, *other↑,
3596- PI,    Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress
- in-vivo, Nor, NA
*TBARS↑, *SOD↑, *Catalase↑, *GSTs↑, *GPx↑, *GSH↑, *ROS↓,
3598- PI,    Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease
- in-vivo, AD, NA
*ROS↓, *Inflam↓, *cognitive↑, *Aβ↓, *tau↓,
1940- PL,    Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
- in-vitro, GBM, LN229 - in-vitro, GBM, U87MG
ROS↑, GSH↓, p38↑, JNK↑, IKKα↑, NF-kB↓, eff↓,
1946- PL,  PI,    Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling
- in-vitro, Liver, NA
eff↑, toxicity↓, TrxR↓, ROS↑, MMP↓, p38↑, Akt↓, mTOR↓,
1947- PL,    Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer
- in-vitro, GC, SGC-7901 - in-vitro, GC, NA
TrxR1↓, ROS↑, ER Stress↑, mtDam↑, selectivity↑, NO↑, TumCCA↑, mt-ROS↑, Casp9↑, Bcl-2↓, Bcl-xL↓, cl‑PARP↑, eff↓, lipid-P↑,
1948- PL,  BNL,    Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy
- in-vitro, GBM, NA
selectivity↑, ROS↑, BioAv↓, BioAv↑, Apoptosis↑, TumCCA↑, eff↑,
1949- PL,    Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor
- in-vitro, CRC, HCT116 - in-vitro, Cerv, HeLa
TrxR↓, selectivity↑, ROS↑, IDO1↓,
1950- PL,    Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549
selectivity↑, ROS↑, SETBP1↓, cl‑Casp9↑, eff↓, FOSB↑,
1951- PL,    Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation
- in-vitro, Lung, A549
ROS↑, lipid-P↑, MMP↓, TumCCA↑, TrxR↓, eff↑,
1952- PL,  5-FU,    Piperlongumine induces ROS accumulation to reverse resistance of 5-FU in human colorectal cancer via targeting TrxR
- in-vivo, CRC, HCT8
ROS↑, TrxR↓, eff↑, p‑Akt↓,
1953- PL,    Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation
- in-vitro, Lung, A549 - in-vitro, Nor, WI38
ROS↑, selectivity↑, TrxR↓, TumCCA↑, GSH?, H2O2↑,
1938- PL,    Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation
- Study, PSA, NA - in-vivo, NA, NA
ROS↑, Apoptosis↑, MMP↓, TumCCA↑, DNAdam↑, STAT3↓, Akt↓, PCNA↓, Ki-67↓, cycD1/CCND1↓, Bcl-2↓, K17↓, HDAC↓, ROS↑, *IL1β↓, *IL6↓, *TNF-α↓, *IL17↓, *IL22↓,
1945- PL,  SANG,    The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer
- in-vitro, Lung, A549
toxicity∅, Apoptosis↑, TumMeta↓, ROS↑, TumCCA↑,
1944- PL,    Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress
- in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2
ER Stress↑, TrxR1↓, ROS↑, eff↓, Bcl-2↓, proCasp3↓, BAX↓, cl‑Casp3↑, TumCCA↑, p‑PERK↑, ATF4↑, TumCG↓, lipid-P↑, selectivity↑,
1943- PL,    Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells
- in-vitro, GBM, NA - in-vivo, NA, NA
selectivity↑, ROS↑, selectivity↑, Prx4↓, *Prx4∅, ER Stress↑, CHOP↑, UPR↑,
1942- PL,    Piperlongumine inhibits antioxidant enzymes, increases ROS levels, induces DNA damage and G2/M cell cycle arrest in breast cell lines
- in-vitro, BC, MCF-7
ROS↑, SOD1↑, Trx1↓, Catalase↓, PrxII↓, ROS↑, GADD45A↑, P21↑, DNAdam↑, TumCCA↑,
1941- PL,    Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer
- in-vitro, HNSCC, NA
selectivity↑, eff↑, ROS↑, toxicity↑, GSH↓, GSSG↑, *GSSG∅, cl‑PARP↑, PUMA↑, GSTP1/GSTπ↓, ChemoSen↑,
1939- PL,    Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP
- in-vitro, HCC, HepG2 - in-vitro, HCC, HUH7 - in-vivo, NA, NA
TumCMig↓, TumCI↓, ER Stress↑, selectivity↑, tumCV↓, ROS↑, GSH↓, eff↓, Ca+2↑, MAPK↑, CHOP↑, Dose↝,
2649- PL,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
AntiCan↑, ROS↑, GSH↓, TrxR↓, Trx↓, Apoptosis↑, TumCCA↑, ER Stress↑, DNAdam↑, ChemoSen↑, BioAv↓,
2966- PL,    A strategy to improve the solubility and bioavailability of the insoluble drug piperlongumine through albumin nanoparticles
- in-vitro, LiverDam, NA
*Half-Life↑, *BioAv↑, eff↑, ROS↑,

Showing Research Papers: 1451 to 1500 of 2174
Prev Page 30 of 44 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2174

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   CYP1A1↑, 1,   CYP2E1↑, 1,   Ferroptosis↑, 2,   GPx4↓, 1,   GSH?, 1,   GSH↓, 16,   GSH/GSSG↓, 1,   GSSG↓, 1,   GSSG↑, 1,   GSTP1/GSTπ↓, 1,   H2O2↑, 1,   Iron↑, 1,   lipid-P↑, 5,   MDA↑, 1,   Nrf1↑, 1,   p‑NRF2↑, 1,   Prx4↓, 1,   PrxII↓, 1,   ROS↓, 1,   ROS↑, 42,   ROS⇅, 1,   mt-ROS↑, 2,   SOD1↑, 1,   Trx↓, 1,   Trx1↓, 1,   TrxR↓, 6,   TrxR1↓, 2,  

Metal & Cofactor Biology ⓘ

TfR1/CD71↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 3,   ATP↓, 1,   CDC25↓, 1,   MMP↓, 10,   mtDam↑, 1,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   CYP3A4↓, 1,   Glycolysis↓, 1,   IDO1↓, 1,  

Cell Death ⓘ

Akt↓, 5,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 17,   BAD↑, 1,   BAX↓, 1,   BAX↑, 5,   Bcl-2↓, 6,   Bcl-xL↓, 1,   BID↑, 2,   Casp↑, 1,   Casp3↑, 5,   cl‑Casp3↑, 2,   proCasp3↓, 1,   Casp9↑, 3,   cl‑Casp9↑, 1,   Chk2↑, 1,   Cyt‑c↑, 4,   Cyt‑c↝, 1,   DR4↑, 2,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↑, 2,   JNK↓, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 3,   Mcl-1↓, 1,   Necroptosis↑, 1,   p27↑, 1,   p38↑, 2,   PUMA↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 2,   SETBP1↓, 1,   tumCV↓, 6,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   ER Stress↑, 5,   GRP78/BiP↑, 1,   p‑PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 4,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNAdam↑, 6,   GADD45A↑, 1,   P53↑, 5,   cl‑PARP↑, 3,   cl‑PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 3,   TumCCA↑, 21,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   ERK↑, 1,   HDAC↓, 1,   mTOR↓, 2,   STAT3↓, 3,   STAT3⇅, 1,   TumCG↓, 8,  

Migration ⓘ

Ca+2↑, 3,   E-cadherin↓, 1,   FOSB↑, 1,   ITGB1↓, 1,   ITGB6↓, 1,   Ki-67↓, 1,   MMP2↓, 3,   MMP9↓, 3,   MMPs↓, 1,   PKCδ↓, 1,   PKCδ↑, 1,   TumCI↓, 3,   TumCMig↓, 5,   TumCP↓, 9,   TumMeta↓, 4,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   ATF4↑, 1,   EGFR↓, 1,   Hif1a↓, 3,   NO↑, 2,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↑, 1,   JAK↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 4,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,   ER(estro)↓, 1,   ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 3,   BioEnh↑, 1,   ChemoSen↑, 7,   CYP1A2↑, 1,   CYP2A3/CYP2A6↓, 1,   Dose↓, 1,   Dose⇅, 1,   Dose↝, 3,   Dose∅, 1,   eff↓, 11,   eff↑, 9,   Half-Life↓, 1,   P450↓, 1,   selectivity↑, 16,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   ERα/ESR1↓, 1,   HER2/EBBR2↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   chemoP↑, 1,   chemoPv↑, 3,   hepatoP↑, 1,   K17↓, 1,   OS↑, 2,   QoL↑, 1,   Risk↓, 1,   toxicity↓, 2,   toxicity↑, 1,   toxicity∅, 1,   Weight↑, 1,  
Total Targets: 168

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 5,   Catalase↓, 1,   Catalase↑, 2,   GPx↑, 1,   GPx1↑, 1,   GSH↓, 1,   GSH↑, 3,   GSR↑, 1,   GSSG∅, 1,   GSTs↑, 2,   lipid-P↓, 1,   Prx4∅, 1,   ROS↓, 7,   ROS↑, 3,   SOD↓, 1,   SOD↑, 2,   SOD1↑, 1,   SOD2↑, 1,   TBARS↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   CYP3A2↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 5,   other↝, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNAdam∅, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   GSK‐3β↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↑, 1,   Fibronectin↓, 1,   MMP2↓, 1,   MMPs↓, 1,   Smad7↑, 1,   TGF-β↓, 1,   Vim↓, 1,   α-SMA↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   IL17↓, 1,   IL1β↓, 1,   IL22↓, 1,   IL6↓, 1,   Inflam↓, 3,   PGE2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 6,   BioEnh↑, 1,   Dose↝, 2,   Dose∅, 1,   eff↑, 3,   Half-Life↑, 1,   Half-Life↝, 1,   P450↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoP↑, 1,   cognitive↑, 3,   hepatoP↑, 3,   memory↑, 1,   motorD↑, 1,   neuroP↑, 2,   toxicity↝, 2,   Weight↓, 1,  
Total Targets: 82

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
121 Silver-NanoParticles
92 Quercetin
88 Magnetic Fields
80 Curcumin
74 Thymoquinone
55 Shikonin
54 Vitamin C (Ascorbic Acid)
52 Resveratrol
49 Berberine
49 Sulforaphane (mainly Broccoli)
47 Lycopene
44 Radiotherapy/Radiation
43 Baicalein
42 Alpha-Lipoic-Acid
40 Selenite (Sodium)
40 Ashwagandha(Withaferin A)
40 Piperlongumine
39 Selenium NanoParticles
38 Artemisinin
38 EGCG (Epigallocatechin Gallate)
37 Betulinic acid
36 Hydrogen Gas
34 Rosmarinic acid
33 Capsaicin
32 Silymarin (Milk Thistle) silibinin
29 Propolis -bee glue
29 Fisetin
28 Apigenin (mainly Parsley)
27 Honokiol
26 Allicin (mainly Garlic)
25 Chemotherapy
25 Phenethyl isothiocyanate
24 Luteolin
24 Magnetic Field Rotating
23 Copper and Cu NanoParticles
23 Chrysin
22 Vitamin K2
21 doxorubicin
21 Gambogic Acid
20 Cisplatin
20 chitosan
20 Chlorogenic acid
20 Juglone
18 Boron
17 salinomycin
17 Parthenolide
16 Urolithin
15 Coenzyme Q10
14 Photodynamic Therapy
14 Auranofin
14 Boswellia (frankincense)
14 Carnosic acid
14 Carvacrol
14 Phenylbutyrate
13 Selenium
13 Ellagic acid
13 Emodin
13 Pterostilbene
12 Caffeic acid
12 VitK3,menadione
11 5-fluorouracil
11 Astaxanthin
11 Dichloroacetate
11 Graviola
11 Piperine
10 Melatonin
10 Ursolic acid
10 diet FMD Fasting Mimicking Diet
10 Ferulic acid
10 Plumbagin
9 SonoDynamic Therapy UltraSound
9 Andrographis
9 Bacopa monnieri
9 borneol
8 Hydroxycinnamic-acid
8 Electrical Pulses
8 Sulfasalazine
8 Hyperthermia
8 Methylene blue
8 Moringa oleifera
8 Propyl gallate
7 3-bromopyruvate
7 Gold NanoParticles
7 Gemcitabine (Gemzar)
7 Metformin
7 immunotherapy
7 Berbamine
7 brusatol
7 Carnosine
7 Celastrol
7 diet Methionine-Restricted Diet
7 Disulfiram
7 HydroxyTyrosol
6 2-DeoxyGlucose
6 Biochanin A
6 Butyrate
6 Chlorophyllin
6 Citric Acid
6 Aflavin-3,3′-digallate
6 Nimbolide
5 Docetaxel
5 Brucea javanica
5 Bromelain
5 erastin
5 Thymol-Thymus vulgaris
5 Chocolate
5 Cinnamon
5 Spermidine
5 Crocetin
5 Huperzine A/Huperzia serrata
5 Garcinol
5 HydroxyCitric Acid
5 Magnolol
5 nicotinamide adenine dinucleotide
5 Rutin
4 chemodynamic therapy
4 EMF
4 Zinc
4 Vitamin E
4 diet Short Term Fasting
4 γ-linolenic acid (Borage Oil)
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 Date Fruit Extract
3 Oxygen, Hyperbaric
3 Shilajit/Fulvic Acid
3 Ginkgo biloba
3 Orlistat
3 MCToil
3 Methylsulfonylmethane
3 Mushroom Lion’s Mane
3 Oleuropein
3 Shankhpushpi
3 Vitamin B1/Thiamine
2 5-Hydroxytryptophan
2 Astragalus
2 Aromatherapy
2 Ascorbyl Palmitate
2 Atorvastatin
2 Aloe anthraquinones
2 beta-glucans
2 Baicalin
2 beta-carotene(VitA)
2 Bufalin/Huachansu
2 Bruteridin(bergamot juice)
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Cat’s Claw
2 Calorie Restriction Mimetics
2 Galantamine
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 Anzaroot, Astragalus fasciculifolius Bioss
1 entinostat
1 Camptothecin
1 Resiquimod
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 D-limonene
1 epirubicin
1 Lapatinib
1 Ras-selective lethal 3
1 Cannabidiol
1 Celecoxib
1 Aspirin -acetylsalicylic acid
1 methylseleninic acid
1 Rivastigmine
1 Docosahexaenoic Acid
1 diet Ketogenic
1 diet Plant based
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 Oleocanthal
1 sericin
1 benzo(a)pyrene
1 Hyperoside
1 Kaempferol
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 xanthohumol
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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