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)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"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⟱
2190- SK,    Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway
- in-vitro, HCC, HCCLM3
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, MMP↓, ROS↑, OCR↓, ATP↓, PKM2↓,
2189- SK,    PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells
- in-vitro, Melanoma, NA
PKM2↓, chemoPv↑, eff↝, lactateProd↓, ROS↑, *ROS?, *PKM2↓,
2188- SK,    Molecular mechanism of shikonin inhibiting tumor growth and potential application in cancer treatment
- Review, Var, NA
ROS↑, EGFR↓, PI3K↓, Akt↓, angioG↓, Apoptosis↑, Necroptosis↑, GSH↓, Ca+2↓, MMP↓, ERK↓, p38↑, proCasp3↑, eff↓, VEGF↓, FOXO3↑, EGR1↑, SIRT1↑, RIP1↑, RIP3↑, BioAv↓, NF-kB↓, Half-Life↓,
2186- SK,    Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line
- in-vitro, HCC, HepG2 - in-vitro, HCC, HCCLM3
Glycolysis↓, PKM2↓, Apoptosis↑, ROS↑, OXPHOS⇅, eff↓,
2203- SK,    Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation
- in-vitro, Lung, NA
TumCP↓, Apoptosis↓, TumCMig↓, TumCI↓, Ferroptosis↑, ERK↓, GPx4↓, 4-HNE↑, ROS↑, GSH↓, ATF3↑, HDAC1↓, ac‑Histones↑,
2229- SK,    Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways
- in-vitro, Melanoma, A375
Apoptosis↑, TumAuto↑, TumCP↓, TumCCA↑, P21↑, cycD1/CCND1↓, ER Stress↑, p‑eIF2α↑, CHOP/DDIT3↑, cl‑Casp3↑, p38↑, LC3B-II↑, Beclin-1↑, ROS↑, eff↓,
2227- SK,    Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901 - in-vitro, Nor, GES-1
selectivity↑, TumCP↓, TumCD↑, ROS↑, MMP↓, Casp↑, Cyt‑c↑, Endon↑, AIF↑, eff↓, ChemoSen↑, TumCCA↑, GSH/GSSG↓, lipid-P↑,
2226- SK,    Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma
- in-vitro, HCC, HUH7 - in-vitro, HCC, Bel-7402
selectivity↑, ROS↑, eff↓, Akt↓, RIP1↓, NF-kB↓,
2225- SK,    Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matter
- in-vitro, Nor, HaCaT
*antiOx↑, *ROS↓, *GSH↑, *GCLC↑, *GSS↑, *Akt↑, *NRF2↑,
2221- SK,    Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression
- in-vitro, Lung, A549
Apoptosis↑, TumCP↓, tumCV↓, Necroptosis↑, P53↑, ROS↑, NF-kB↓,
2220- SK,    Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades
- in-vivo, Nor, NA
*RenoP↑, *ROS↓, *SIRT1↓, *NRF2↑, *HO-1↑, *GSH↑, *TAC↑, *SOD↑, *MDA↓, *NO↓, *iNOS↓, *NHE3↑, *PI3K↑,
2219- SK,    Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways
- in-vitro, Nor, HaCaT
*MMP↓, *ROS↑, *Casp3↑, *TumCG↓,
2215- SK,  doxoR,    Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice
- in-vivo, Nor, NA
*cardioP↑, *ROS↓, *Inflam↓, *Mst1↓, *NRF2↑, *eff↓, *antiOx↑, *SOD↑, *GSH↑, *TNF-α↓, BAX↓, Bcl-2↑,
2214- SK,    Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway
- in-vitro, Nor, NA
*NRF2↑, *HO-1↑, *NQO1↑, *antiOx↑, *neuroP↑, *ROS↓, *MDA↓, *SOD↑, GSH↑,
2210- SK,    Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway
- in-vitro, BC, MGC803
TumCA↓, TumCI↓, TumCMig↓, MMP2↓, MMP7↓, TLR2↓, p65↓, NF-kB↓, eff↑, ROS↑,
2202- SK,    Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification
- in-vitro, Var, NA
Iron↑, Ferroptosis↑, pH↝, H2O2↑, ROS↑, Fenton↑, GSH↓, GPx4↓, lipid-P↑,
2218- SK,    Shikonin Alleviates Endothelial Cell Injury Induced by ox-LDL via AMPK/Nrf2/HO-1 Signaling Pathway
- in-vitro, Nor, HUVECs
*Dose↝, *Apoptosis↓, *Casp3↓, *Bcl-2↑, *Inflam↓, *VCAM-1↓, *ICAM-1↓, *E-sel↓, *ROS↓, *SOD↑, *AMPK↑, *NRF2↑, *HO-1↑, *TNF-α↓, *IL1β↓, *IL6↓,
3045- SK,    Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)
- in-vitro, PC, MIA PaCa-2
ECAR↓, Glycolysis↓, ATP↓, PKM2↓, TumCMig↓, Ca+2↑, GlucoseCon↓, lactateProd↓, MMP↓, ROS↑,
3042- SK,    The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathways
- in-vivo, Nor, NA
*TNF-α↓, *IL1β↓, *IL6↓, *IFN-γ↓, *ALAT↓, *AST↓, *MPO↓, *ROS↓, *JNK↓, *ERK↓, *p38↓, *NF-kB↓, *p‑IKKα↓, *SOD↑, *GSH↑, *HO-1↑, *NRF2↑, *hepatoP↑,
3041- SK,    Promising Nanomedicines of Shikonin for Cancer Therapy
- Review, Var, NA
Glycolysis↓, TAMS↝, BioAv↓, Half-Life↝, P21↑, ERK↓, ROS↑, GSH↓, MMP↓, TrxR↓, MMP13↓, MMP2↓, MMP9↓, SIRT2↑, Hif1a↓, PKM2↓, TumCP↓, TumMeta↓, TumCI↓,
3040- SK,    Pharmacological Properties of Shikonin – A Review of Literature since 2002
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA
*Half-Life↝, *BioAv↓, *BioAv↑, *BioAv↑, *Inflam↓, *TNF-α↓, *other↑, *MPO↓, *COX2/PTGS2↓, *NF-kB↑, *STAT3↑, *antiOx↑, *ROS↓, *neuroP↑, *SOD↑, *Catalase↑, *GPx↑, *Bcl-2↑, *BAX↓, cardioP↑, AntiCan↑, NF-kB↓, ROS↑, PKM2↓, TumCCA↑, Necroptosis↑, Apoptosis↑, DNAdam↑, MMP↓, Cyt‑c↑, LDH↝,
3047- SK,    Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL-6/STAT3 signaling pathway
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
TumCG↓, p‑STAT3↓, ADAM17↓, Apoptosis↑, Casp3↑, cl‑PARP↑, cycD1/CCND1↓, cycE/CCNE↓, TumCCA↑, JAK1?, p‑JAK1↓, p‑JAK2↓, p‑eIF2α↑, eff↓, ROS↑, IL6↓,
2469- SK,    Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2
- in-vitro, Lung, H1975
Apoptosis↑, Pyro↑, Casp↑, cl‑PARP↑, GSDME↑, ROS↑, COX2/PTGS2↓, PDK1↓, Akt↓, ERK↓, eff↓, eff↓, eff↑,
5102- SK,  GEM,    Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway
TumCG↓, ChemoSen↑, NF-kB↓, PCNA↓, Ki-67↓, p‑EGFR↓, ROS↑, TumCCA↑, P53↑, JNK↑, Akt↓,
5101- SK,    Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis
- vitro+vivo, CRC, SW-620 - vitro+vivo, CRC, HCT116
Apoptosis↑, TumAuto↑, Gal1↑, TumCP↓, ROS↑, eff↑,
5100- SK,    Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression
- vitro+vivo, NPC, NA
TumCP↓, RIP1↑, ROS↑, Necroptosis↑, Casp3↑, Casp8↑, eff↓, TumCG↓,
1280- SK,    Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells
- in-vitro, GC, AGS
ROS↑, Casp3↑, P53↑, NRF2↓,
1284- SK,    Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy
- in-vitro, Melanoma, RPMI-8226 - in-vitro, Melanoma, U266
Ferroptosis↑, LDH↓, ROS↑, Iron↑, lipid-P↑, ATP↓, HMGB1↓, GPx4↓, MDA↑, SOD↓, GSH↓,
2009- SK,    Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancer
- in-vitro, Bladder, NA
TumCG↓, selectivity↑, *toxicity∅, Necroptosis↑, ROS↑, p62↑, Keap1↑, *NRF2↑, eff↑,
2008- SK,  Cisplatin,    Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo
- in-vitro, CRC, HCT116 - in-vivo, NA, NA
ChemoSen↑, selectivity↑, i-ROS↑, DNAdam↑, MMP↓, TumCCA↑, eff↓, *toxicity↓,
2007- SK,    Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells
- in-vitro, lymphoma, U937 - in-vitro, BC, MCF7 - in-vitro, BC, SkBr3 - in-vitro, CRC, HCT116 - in-vitro, OS, U2OS - NA, Nor, RPE-1
tumCV↓, selectivity↑, Dose↝, other↑, MMP↓, ROS↑, DNAdam↑, Ca+2↑, Casp9↑, Cyt‑c↑, *toxicity↓,
2010- SK,    Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway
- in-vitro, Lung, H1975 - in-vitro, Lung, H1650 - in-vitro, Nor, CCD19
EGFR↓, selectivity↑, Casp↑, PARP↑, Apoptosis↑, ROS↑, eff↓, selectivity↑,
2011- SK,    Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling
- in-vitro, Nor, HL7702 - in-vivo, Nor, NA
*NRF2↑, *hepatoP↑, *ALAT↓, *AST↓, *MPO↓, *ROS↓, *GSH↑,
1342- SK,    RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species
- in-vitro, GBM, NA - in-vivo, NA, NA
RIP1↑, RIP3↑, DNAdam↑, ROS↑, GSH↓,
1343- SK,    Simple ROS-responsive micelles loaded Shikonin for efficient ovarian cancer targeting therapy by disrupting intracellular redox homeostasis
- in-vitro, Ovarian, A2780S - in-vivo, NA, A2780S
*BioAv↓, ROS↑, GSH↓, TumCG↓,
1344- SK,    Novel multiple apoptotic mechanism of shikonin in human glioma cells
- in-vitro, GBM, U87MG - in-vitro, GBM, Hs683 - in-vitro, GBM, M059K
ROS↑, GSH↓, MMP↓, P53↑, cl‑PARP↑, Catalase↓, SOD1↑, Bcl-2↓, BAX↑, eff↓,
1345- SK,    The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway
- in-vitro, AML, HL-60
CD14↑, CD11b↑, ROS↑, GSH↓, GSH/GSSG↓, GPx↑, Catalase↓, Diff↑,
1346- SK,    An Oxidative Stress Mechanism of Shikonin in Human Glioma Cells
- in-vitro, GBM, U87MG - in-vitro, GBM, Hs683
NRF2↓, ROS↑, Apoptosis↑, Cyt‑c↑, GSH↓, MMP↓, P53↑, HO-1⇅,
1312- SK,    Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells
- in-vitro, OS, 143B
ROS↑, p‑ERK↑, Bcl-2↓, cl‑PARP↑, Apoptosis↑, TumCCA↑, Bcl-2↑, proCasp3↓,
965- SK,    Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW-620
Hif1a↓, ROS↓, mTOR↓, p70S6↓, 4E-BP1↓, eIF2α↓, TumCCA↑, TumCP↓, Half-Life↝,
1050- SK,    Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation
- in-vitro, Colon, CT26
HSP70/HSPA5↑, ROS↑, PKM2↓,
1073- SK,  Chemo,    Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells
- in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
PAK1↓, TumCP↓, Apoptosis↑, ChemoSen↑, ROS↑,
1133- SM,    Salvianolic Acid A, a Component of Salvia miltiorrhiza, Attenuates Endothelial-Mesenchymal Transition of HPAECs Induced by Hypoxia
- in-vitro, Nor, HPAECs
*ROS↓, *p‑Smad1↑, *p‑SMAD5↑, *SMAD2↓, *SMAD3↓, *p‑ERK↓, *p‑Cofilin↓,
1193- SM,    Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways
- in-vivo, Alcohol, NA - in-vitro, Liver, HepG2
*p‑AMPK↑, *SIRT1↑, *NRF2↑, *CYP2E1↓, *lipoGen↓, *ROS↓, *Inflam↓,
4891- Sper,    Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms
- Review, Var, NA - Review, AD, NA
TumCCA↑, TumCP↓, TumCG↓, *Inflam↓, *antiOx↑, *neuroP↑, *cognitive↑, *Aβ↓, *mitResp↑, AntiCan↑, TumCD↑, TumAuto↑, *AntiAge↑, LC3B-II↑, ATG5↑, Beclin-1↑, mt-ROS↑, H2O2↑, Apoptosis↑, *ROS↑, ChemoSen↑, MMP↓, Cyt‑c↑,
4892- Sper,  erastin,    Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer
- in-vitro, Pca, PC3 - in-vivo, Pca, NA
Ferroptosis↑, lipid-P↑, Iron↑, eff↑, HO-1↑, NRF2↑, ROS↑, AntiTum↑, eff↓,
4894- Sper,    Application of Spermidine in Cancer Research Models: Notes and Protocols
- Review, Var, NA
TumAuto↑, AntiTum↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑,
4897- Sper,    Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms
- Review, Var, NA
Inflam↓, TumAuto↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑, Bcl-2↓,
1512- Squ,    Combination therapy in combating cancer
- Review, NA, NA
ChemoSideEff↓, *ROS↓, *GSH↑, eff↑, chemoP↑,
1017- SSE,    Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis
- vitro+vivo, CRC, NA
Akt↓, β-catenin/ZEB1↓, cycD1/CCND1↓, survivin↓, Apoptosis↑, ROS↑,

Showing Research Papers: 2401 to 2450 of 2689
Prev Page 49 of 54 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2689

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

4-HNE↑, 1,   ATF3↑, 1,   Catalase↓, 2,   Fenton↑, 1,   Ferroptosis↑, 4,   GPx↑, 1,   GPx4↓, 3,   GSH↓, 10,   GSH↑, 1,   GSH/GSSG↓, 2,   H2O2↑, 2,   HO-1↑, 1,   HO-1⇅, 1,   Iron↑, 3,   Keap1↑, 1,   lipid-P↑, 4,   MDA↑, 1,   NRF2↓, 2,   NRF2↑, 1,   OXPHOS⇅, 1,   ROS↓, 1,   ROS↑, 36,   i-ROS↑, 1,   mt-ROS↑, 1,   SOD↓, 1,   SOD1↑, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   ATP↓, 3,   MMP↓, 13,   OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ECAR↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   ac‑Histones↑, 1,   lactateProd↓, 2,   LDH↓, 1,   LDH↝, 1,   PDK1↓, 1,   PKM2↓, 7,   SIRT1↑, 1,   SIRT2↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 5,   Apoptosis↓, 1,   Apoptosis↑, 17,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 3,   Bcl-2↑, 2,   Casp↑, 3,   Casp3↑, 3,   cl‑Casp3↑, 1,   proCasp3↓, 1,   proCasp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 7,   Endon↑, 1,   Ferroptosis↑, 4,   GSDME↑, 1,   JNK↑, 1,   Necroptosis↑, 5,   p38↑, 2,   Pyro↑, 1,   RIP1↓, 1,   RIP1↑, 3,   survivin↓, 1,   TumCD↑, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

p70S6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   eIF2α↓, 1,   p‑eIF2α↑, 2,   ER Stress↑, 1,   HSP70/HSPA5↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↑, 2,   LC3B-II↑, 2,   p62↑, 1,   TumAuto↑, 5,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 4,   P53↑, 5,   PARP↑, 1,   cl‑PARP↑, 4,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 9,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

4E-BP1↓, 1,   Diff↑, 1,   ERK↓, 4,   p‑ERK↑, 1,   FOXO3↑, 1,   HDAC1↓, 1,   mTOR↓, 1,   PI3K↓, 1,   p‑STAT3↓, 1,   TumCG↓, 6,  

Migration(tgid=13) ⓘ

Ca+2↓, 1,   Ca+2↑, 2,   CD11b↑, 1,   Ki-67↓, 1,   MMP13↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 1,   PAK1↓, 1,   RIP3↑, 2,   TumCA↓, 1,   TumCI↓, 4,   TumCMig↓, 4,   TumCP↓, 11,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 2,   p‑EGFR↓, 1,   EGR1↑, 1,   Hif1a↓, 2,   TAMS↝, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD14↑, 1,   COX2/PTGS2↓, 1,   Gal1↑, 1,   HMGB1↓, 1,   IL6↓, 1,   Inflam↓, 1,   JAK1?, 1,   p‑JAK1↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 6,   p65↓, 1,   TLR2↓, 1,  

Cellular Microenvironment(tgid=17) ⓘ

ADAM17↓, 1,   pH↝, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   ChemoSen↑, 5,   Dose↝, 1,   eff↓, 13,   eff↑, 6,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 2,   selectivity↑, 7,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 2,   p‑EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,   LDH↓, 1,   LDH↝, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2,   AntiTum↑, 2,   cardioP↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   ChemoSideEff↓, 1,  
Total Targets: 158

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5,   Catalase↑, 1,   CYP2E1↓, 1,   GCLC↑, 1,   GPx↑, 1,   GSH↑, 6,   GSS↑, 1,   HO-1↑, 4,   MDA↓, 2,   MPO↓, 3,   NQO1↑, 1,   NRF2↑, 9,   ROS?, 1,   ROS↓, 11,   ROS↑, 2,   SOD↑, 6,   TAC↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mitResp↑, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 2,   AMPK↑, 1,   p‑AMPK↑, 1,   lipoGen↓, 1,   PKM2↓, 1,   SIRT1↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,   Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↑, 2,   Casp3↓, 1,   Casp3↑, 1,   iNOS↓, 1,   JNK↓, 1,   p38↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,   p‑ERK↓, 1,   Mst1↓, 1,   PI3K↑, 1,   STAT3↑, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

p‑Cofilin↓, 1,   E-sel↓, 1,   p‑Smad1↑, 1,   SMAD2↓, 1,   SMAD3↓, 1,   p‑SMAD5↑, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,  

Barriers & Transport(tgid=15) ⓘ

NHE3↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   p‑IKKα↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 5,   NF-kB↓, 1,   NF-kB↑, 1,   TNF-α↓, 4,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 2,   Dose↝, 1,   eff↓, 1,   Half-Life↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2,   AST↓, 2,   IL6↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 2,   neuroP↑, 3,   RenoP↑, 1,   toxicity↓, 2,   toxicity∅, 1,  
Total Targets: 78

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
122 Silver-NanoParticles
99 Curcumin
95 Quercetin
91 Magnetic Fields
74 Thymoquinone
58 Resveratrol
56 Vitamin C (Ascorbic Acid)
55 Radiotherapy/Radiation
55 Shikonin
50 Berberine
50 Sulforaphane (mainly Broccoli)
47 Lycopene
47 Hydrogen Gas
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
34 Rosmarinic acid
34 Fisetin
33 Capsaicin
32 Silymarin (Milk Thistle) silibinin
29 Chemotherapy
29 Propolis -bee glue
28 Cisplatin
28 Copper and Cu NanoParticles
28 Apigenin (mainly Parsley)
28 Honokiol
26 doxorubicin
26 Allicin (mainly Garlic)
26 Emodin
26 Gambogic Acid
25 Luteolin
25 Magnetic Field Rotating
25 Phenethyl isothiocyanate
23 Chlorogenic acid
23 Chrysin
22 Vitamin K2
21 chitosan
20 Coenzyme Q10
20 Juglone
19 isoquercitrin
19 isoorientin
18 Boron
18 Ferulic acid
17 salinomycin
17 Parthenolide
16 Urolithin
15 Caffeic acid
15 chaetocin
15 Ellagic acid
15 Eugenol
15 Isoliquiritigenin
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 Gallic acid
13 Pterostilbene
12 Melatonin
12 Graviola
12 HydroxyTyrosol
12 Isobavachalcone
12 VitK3,menadione
11 5-fluorouracil
11 Astaxanthin
11 Cinnamon
11 Cynaropicrin
11 Hyperthermia
11 Isovitexin
11 Piperine
10 Beta-Caryophyllene
10 α-Bisabolol / Chamomile oil
10 Ursolic acid
10 diet FMD Fasting Mimicking Diet
10 Hyperoside
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 Hydroxycinnamic-acid
9 Diclofenac
9 Ginkgo biloba
8 3-bromopyruvate
8 Disulfiram
8 Electrical Pulses
8 Sulfasalazine
8 Methylene blue
8 Moringa oleifera
8 Propyl gallate
7 EMF
7 Gold NanoParticles
7 Gemcitabine (Gemzar)
7 Metformin
7 immunotherapy
7 Berbamine
7 brusatol
7 Carnosine
7 Celastrol
7 diet Methionine-Restricted Diet
7 eicosapentaenoic acid
7 Formononetin
7 Garcinol
7 Ginkgetin
6 2-DeoxyGlucose
6 Rutin
6 Phyllanthus emblica/Emblica officinalis/Amla / Indian Gooseberry
6 Anethole/trans-Anethole
6 Docetaxel
6 Biochanin A
6 Butyrate
6 Mung Bean Sprouts
6 Chlorophyllin
6 Chocolate
6 Citric Acid
6 Carvone
6 Cynara scolymus/Globe Artichoke/Artichoke Extract
6 Aflavin-3,3′-digallate
6 Fenbendazole
6 Fucoidan
6 HydroxyCitric Acid
6 Vitexin
5 1,8-Cineole
5 Brucea javanica
5 Bromelain
5 erastin
5 Thymol-Thymus vulgaris
5 Cichoric acid / Chicoric acid
5 Spermidine
5 Huperzine A/Huperzia serrata
5 Date Fruit Extract
5 Docosahexaenoic Acid
5 Evodiamine
5 Gossypol/AT-101
5 Magnolol
5 nicotinamide adenine dinucleotide
4 chemodynamic therapy
4 Zinc
4 Vitamin E
4 Cucurbitacin
4 diet Short Term Fasting
4 Ginkgo biloba-EGb 761
4 Geraniol
4 Ginkgolide B
4 Ginseng
4 γ-linolenic acid (Borage Oil)
4 Hibiscus sabdariffa
4 Inositol
4 Linalool
4 Magnesium
4 Naringin
4 Taurine
3 5-Aminolevulinic acid
3 Anthocyanins
3 Glucose
3 temozolomide
3 Black phosphorus
3 Paclitaxel/Taxol
3 Caffeic Acid Phenethyl Ester (CAPE)
3 Catechins
3 Choline
3 Dihydrocaffeic Acid
3 Oxygen, Hyperbaric
3 ferumoxytol
3 flavonoids
3 Shilajit/Fulvic Acid
3 Ginger/6-Shogaol/Gingerol
3 Grapeseed extract
3 Orlistat
3 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
3 MCToil
3 Methylsulfonylmethane
3 Mushroom Lion’s Mane
3 Myricetin
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 buckwheat sprouts
2 Cat’s Claw
2 Celecoxib
2 methotrexate
2 Carica papaya leaf extract
2 Calorie Restriction Mimetics
2 Galantamine
2 CUSP9
2 Folic Acid, Vit B9
2 Galloflavin
2 Germanium Organic/Ge-132 / propagermanium (organogermanium)
2 iodine
2 isoflavones
2 Potassium
2 Kaempferol
2 Methyl Jasmonate
2 Methylglyoxal
2 Vitamin B3,Niacin
2 Niclosamide (Niclocide)
2 Pachymic acid
2 Sanguinarine
2 Psoralidin
2 Radio Frequency
2 Rauwolfia serpentina/Indian Snakeroot
2 Sesame seeds and Oil
2 Iron
2 Salvia miltiorrhiza
2 triptolide
2 Vitamin D3
1 cetuximab
1 Annona atemoya Leaf Extract
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 Angelica archangelica / Garden Angelica
1 Anti-oxidants
1 Sorafenib (brand name Nexavar)
1 tamoxifen
1 almonertinib
1 epirubicin
1 Lapatinib
1 Ras-selective lethal 3
1 Chyawanprash
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 olaparib/LYNPARZA
1 verapamil
1 hydroxychloroquine
1 Ginkgolic acids
1 Genistein (soy isoflavone)
1 Germanium inorganic
1 hydrogen sulfide
1 Helleborus niger extracts – Christmas Rose
1 Rapamycin
1 Indole-3-carbinol
1 Inoscavin A
1 Butein
1 Scopoletin
1 Morin
1 Ivermectin
1 lambertianic acid
1 Myrrh
1 N-Acetyl-Cysteine
1 No Product/Mechanism Only
1 Oleocanthal
1 sericin
1 Polyphenols
1 benzo(a)pyrene
1 Rhein
1 Perilla
1 Salvia officinalis
1 Oxaliplatin
1 Scoulerine
1 polyethylene glycol
1 acetaminophen
1 Silicic Acid
1 Squalene
1 Osimertinib
1 Adagrasib
1 Glutathione
1 statins
1 Safflower yellow
1 Terminalia bellirica
1 Triphala
1 Vanillic Acid
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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