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⟱
1905- AgNPs,    Evaluation of the effect of silver and silver nanoparticles on the function of selenoproteins using an in-vitro model of the fish intestine: The cell line RTgutGC
- in-vivo, Nor, NA
*TrxR↓, TrxR activity was inhibited by AgNO3 (0.4 µM) and cit-AgNP (1, 5 µM).
*ROS∅, Oxidative stress was not observed at any of the doses of AgNO3 or cit-AgNP tested
GPx↑, In this study, we show that dissolved and nano Ag can inhibit selenoenzymes activity (GPx and TrxR) in fish intestinal cells (RTgutGC).

2000- AL,    Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, NA
selectivity↑, The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells.
TumCG?,
*toxicity∅, no substantial cytotoxicity was seen in normal Vero cells
ROS↑, TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP
MMP↓,
TumCCA↑, increased the percentage of cells in the G2/M phase
P53↑, ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins.
Bcl-2↓,
p‑Akt↓,
p‑p38↓,
*ROS∅, Vero normal cells did not display the unusual morphological alteration and reduction in cell viability. ROS production revealed a 1.21 % ROS level only in control cells that is typically seen in healthy cells.

1999- Api,  doxoR,    Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation
- in-vitro, Nor, NRK52E - in-vitro, Nor, MPC5 - in-vitro, BC, 4T1 - in-vivo, NA, NA
neuroP↑, APG has a protective role against DOX-induced nephrotoxicity
ChemoSen∅, without weakening DOX cytotoxicity in malignant tumors.
RenoP↑, potential protective agent against renal injury. attenuate renal toxicity in cancer patients treated with DOX.
selectivity↑, APG maintained the cytotoxicity of DOX to tumor cells but not to renal cells. APG alone exhibited a prominent cytotoxic effect on 4T1 cells (Fig. 9E), but not on normal renal cells, at the same concentration
chemoP↑, Furthermore, APG revealed a dose-dependent improvement in normal renal cells against DOX-induced injury (Fig. 9E), with an exacerbation observed in 4T1 cells
ROS↑, Our in vivo study revealed that DOX caused a severe reduction in SOD activity and GSH levels, accompanied by an increase in MDA, leading to the overproduction of ROS and induction of oxidative injuries.
*ROS∅, Noteworthily, these changes were suppressed by APG(meaning on normal cells), consistent with several previous reports
*antiOx↑, APG has a similar antioxidative role as NAC and scavenges DOX-induced oxygen radicals and inhibits apoptosis significantly, implying that antioxidative stress is one of the main mechanisms through which APG protects renal tubular cells against DOX cy
*toxicity↓, We confirmed that APG mitigated the toxicity of DOX on normal renal cells by inhibiting oxidative stress, inflammation, and apoptosis.

3388- ART/DHA,    Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation
- in-vitro, Lung, A549 - in-vitro, Nor, GP-293 - in-vitro, BC, MDA-MB-231
NRF2↑, ATT upregulated Nrf2 in the MB231 cells . ATT increased Nrf2 levels at low doses ranging from 1 to 5 μM
ROS∅, ATT does not increase ROS production and cannot active Nrf2 by inducing oxidative stress

1142- Ash,    Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer
- Review, BC, MCF-7 - NA, BC, MDA-MB-231 - NA, Nor, HMEC
Apoptosis↑,
ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
DNAdam↑,
OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
Bcl-2↓,
XIAP↓,
survivin↓,
DR5↑,
IKKα↓,
NF-kB↓,
selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS

5396- Ash,    Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology
- Review, Var, NA
selectivity↑, WS was shown to impede the growth of new cancer cells, but not normal cells,
ROS↑, help induce programmed death of cells by generating reactive oxygen species (ROS), and sensistize cancer cells to apoptosis
Apoptosis↑,
ChemoSen↑, Pre-clinical studies in several cancer types have shown up to 80% inhibition using combination chemotherapy [19].
RadioS↑, It was not until 1996, that WFA’s radiosensitizer activity was reported that caused V79 cell survival reduction where 1-h pre-treatment at 2.1 µM dose before radiation significantly killed cells
NF-kB↓, inhibiting NF-κB activation
ER-α36↓, WFA, it was found the phytochemical downregulated the estrogen receptor-α (ER-α) protein in MCF-7 cells.
P53↑, WFA selectively activated p53 in tumor cells treated with the leaf extract of Ashwagandha [71] leading to growth arrest and apoptosis.
*ROS∅, opposed to the normal human mammary epithelial cells (HMEC) [72] which did not increase ROS production.
γH2AX↑, The group found an increase in γ-H2AX and number of cells expressing the phosphorylated form which is a marker for DNA damage in WFA treated MCF-7 cells.
DNAdam↑,
MMP↓, As ROS is well known to affect mithochondrial membrane potential, they found a change in mitochondrial membrane potential and altered mitochondrial morphology in WFA treated cells.
XIAP↓, XIAP (X-linked inhibitor of apoptosis protein), cIAP-2 (cellular inhibitor of apoptosis protein-2) and Survivin proteins were found to be reduced in MDA-MB-231 and MCF-7 cells when treated with WFA
IAP1↓,
survivin↓,
SOD↓, figure 2
Dose↝, doses of 3 and 4 mg/kg and the authors found 59% reduction of tumor and polyp initiation and progression in the WFA treated mice compared to the controls [80].
IL6↓, WFA downregulated expression of inflammatory markers in these tumors such as IL-6, TNF-α, COX-2 along with pro-survival markers such as pAkt, Notch1 and NF-κβ [80].
TNF-α↓,
COX2↓,
p‑Akt↓,
NOTCH1↓,
FOXO↑, figure 3 prostrate cancer
Casp↑,
MMP2↓,
CSCs↓, WFA treatment significantly reduced ALDH+ CSC population, whereas Cisplatin treatment increased CSC population.
*ROS↓, WFA was found to increase cellular survival in simulated injury and in H2O2-induced cell apoptosis along with inhibition of oxidative stress.
*SOD2↑, Thus, via upregulation of SOD2, SOD3, Prdx-1 by H2O2, WFA treatment leads to inhibition of the antioxidants and Akt-dependent improvement of cardiomyocyte caspase-3 [103].
chemoP↑, First, given the safety record of WS, it can be used as an adjunct therapy that can aid in reducing the adverse effects associated with radio and chemotherapy due to its anti-inflammatory properties.
ChemoSen↑, Second, WS can also be combined with other conventional therapies such as chemotherapies to synergize and potentiate the effects due to radiotherapy and chemotherapy due to its ability to aid in radio- and chemosensitization, respectively.
RadioS↑,

1355- Ash,    Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, HMEC
eff↑, WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). ****
mt-ROS↑, WA-induced apoptosis in human breast cancer cells is mediated by mitochondria-derived ROS
mitResp↓,
OXPHOS↓, WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity.
compIII↑,
BAX↑,
Bak↑,
other↓, Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) overexpression confers protection against WA-induced ROS production and apoptosis
ATP∅, steady-state levels of ATP were unaffected by WA treatment in either cell line
*ROS∅, but not in a normal human mammary epithelial cell line (HMEC). WA treatment caused ROS production in breast cancer cells, HMEC were resistant to pro-oxidant effect of this agent.

2003- Ash,    Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, Nor, TIG-1 - in-vitro, PC, LNCaP
TumCD↑, We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells
selectivity↑, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD)
cFos↑, WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1.
ROS↑, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts
*ROS∅, but not in normal fibroblasts
HSP70/HSPA5↑,
Apoptosis↑, WA induces apoptosis mediated by ER stress
ER Stress↑,
TumCCA↑, WA induces autophagy in breast cancer cells, but the detailed mechanism remains elusive

4817- ASTX,    Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53
- in-vitro, GBM, U251
Dose⇅, At high concentrations (20–40 μM), AXT triggered apoptosis in U251-MG cells, as it has been previously shown in other cancer cell lines. However, low concentrations (4–8 μM) of AXT were found to upregulate the proliferative cell cycle.
ROS∅, low concentrations, AXT did not affect the intracellular ROS levels, while the superoxide dismutase activity increased moderately.
SOD↑,
CDK1↑, Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53
P53↓,
TumCP⇅, we found that U251-MG cells show a biphasic response to AXT, that is low doses of AXT have a proliferative effect, with a maximum survival increase of 130.4 ± 2.4% after treatment with 5 µM of AXT, while AXT concentrations over 20 µM have an apoptoti
ROS↑, Treatment with High AXT Concentrations Increased Intracellular ROS Levels while Low AXT Concentrations did not Affect ROS Levels

1535- Ba,    Baicalein May Act as a Caloric Restriction Mimetic Candidate to Improve the Antioxidant Profile in a Natural Rodent Model of Aging
- in-vivo, Nor, NA
*antiOx↑, Baicalein supplementation in male Wistar rats significantly alleviated pro-oxidant markers and improved antioxidant profile.
*ROS∅, Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR.
*CRM↑, conclude that Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR.

1531- Ba,    Proteomic analysis of the effects of baicalein on colorectal cancer cells
- in-vitro, CRC, DLD1 - in-vitro, CRC, SW48
TumCP↓,
ROS↓, reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6)
Prx6↑,
eff↓, Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation
TumCCA↑, after baicalein treatment, the percentage of the S phase de- creased; those in the G1 phase rose to 45%, whereas those in the S and G2/M phase diminished to 22% and 33%.
ROS↝, Knocking down PRDX6 expression significantly promoted ROS product of the baicalein-treated DLD-1 cells
*ROS∅, baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

2479- Ba,    Baicalein Overcomes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Resistance via Two Different Cell-Specific Pathways in Cancer Cells but not in Normal Cells
- in-vitro, HCC, SW480 - in-vitro, Pca, PC3
12LOX↓, Baicalein is also known as a selective 12-lipoxygenase (12-LOX) inhibitor
DR5↑, Baicalein induces DR5 mRNA and protein expression in SW480 cells
CHOP↑, CHOP is increased by baicalein and responsible for DR5 up-regulation in SW480 cells
ROS↑, ROS are responsible for DR5 up-regulation in PC3 cells, but not in SW480 cells
*ROS∅,
selectivity↑, ROS are responsible for DR5 up-regulation in PC3 cells, but not in SW480 cells

2023- BBR,    Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor
- in-vitro, Colon, NA - in-vitro, Nor, YAMC
TumCD↑, Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells.
*toxicity↓, In contrast, YAMC(normal) cells were not sensitive to berberine-induced cell death. less cytotoxic effects on normal colon epithelial cells.
selectivity↑, see figure 2
ROS↑, berberine-stimulated ROS production
*ROS∅, ROS production in a concentration-dependent manner only in IMCE cells, but not in YAMC cells. In YAMC cells, berberine did not induce ROS production
MMP↓, berberine induced mitochondrial depolarization in a concentration-dependent manner in IMCE cells, but not in YAMC cells
*MMP∅, but not in YAMC cells
PARP↑, Berberine Activation of PARP
BioAv↝, absorption of berberine by YAMC is lower than that by IMCE cells

2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24/HTB-9 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB/CCNB1↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1/CCNA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,

5697- BRU,    Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous Cell Carcinoma
- in-vitro, HNSCC, NA
NRF2↓, Brusatol, a Nrf2 Inhibitor
STAT3↓, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells.
proCasp3↑, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells.
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Hif1a↓, BT also induced the degradation of HIF-1α
cMyc↓, BT suppressed c-Myc expression
JNK↑, BT was found to activate JNK and p38 MAPK pathways with concurrent inhibition of proinflammatory signaling pathways such as NF-κB and STAT3
MAPK↑,
tumCV↓, BT Reduced the Cell Viability of HNSCC Cells
ROS∅, BT treatment did not significantly alter the level of ROS

2014- CAP,    Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells
- in-vitro, PC, Bxpc-3 - in-vitro, Nor, HPDE-6 - in-vivo, PC, AsPC-1
ROS↑, ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells
*ROS∅, but not in normal HPDE-6 cells
selectivity↑, only small ~1.2fold ROS increase in normal cell
compI↓, capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity
compIII↓, and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively
eff↑, which was attenuable by SOD, catalase and EUK-134.
selectivity↑, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells
ATP↓, ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells
Cyt‑c↑, release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential
Casp9↑,
Casp3↑,
MMP↓,
SOD↓, mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls
GSH/GSSG↓, mice orally fed with 2.5 mg/kg capsaicin
Apoptosis↑, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
*toxicity∅, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
GSH↓, Taken together, our results suggest that depletion of GSH level and inhibition of SOD, catalase and GPx by capsaicin disturbs the cellular redox homeostasis resulting in increased oxidative stress.
Catalase↓,
GPx↓,
Dose↝, 13.2 mg dose of capsaicin for a 60 kg person

2020- CAP,    Capsaicinoids and Their Effects on Cancer: The “Double-Edged Sword” Postulate from the Molecular Scale
- Review, Var, NA
AntiTum↑, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer,
selectivity↑, while non-cancer cells tend to have greater tolerance
TRPV1↑, activation or phosphorylation of TRPV1
MMP↓, leads to cell membrane depolarization through the influx of Na2+ and Ca2+,
Ca+2↑,
ER Stress↑, endoplasmic reticulum stress [73], and the inhibition of angiogenesis
angioG↓,
Casp3?, increase in caspase-3 activation, PARP-1 cleavage
cl‑PARP↑,
selectivity↑, oxidative stress threshold reached by these could be potentially higher than that caused in normal cells (tNOX−) when exposed to CAP, possibly also contributing to the selectivity of its effects
ROS↑, increase in the production of reactive oxygen species (ROS),
*ROS∅, Remarkably, in this same work, cells derived from the normal epithelium of human pancreatic ducts (HPDE6-E6E7) showed high tolerance to the same treatment by keeping their ROS levels stable
selectivity↑, In this sense, non-transformed human astrocytes from a primary culture showed greater tolerance to CAP, as they did not experience any of the mentioned effects when exposed to the same treatment

1144- CHr,    8-bromo-7-methoxychrysin-induced apoptosis of hepatocellular carcinoma cells involves ROS and JNK
- in-vitro, HCC, HepG2 - in-vitro, HCC, Bel-7402 - in-vitro, Nor, HL7702
Casp3↑,
*ROS∅, BrMC did not affect ROS generation in L-02 cells
ROS↑,
JNK↑,
*toxicity↓, BrMC had little effect on human embryo liver L-02 cells

1600- Cu,    Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis
- Review, NA, NA
ER Stress↑, Endoplasmic reticulum stress, mediated by reactive oxygen species (ROS), is thought to induce an antitumor immune response
ROS↑,
AntiTum↑,
GSH↓, Li and coworkers recently reported that copper-cysteine nanoparticles could contribute to both oxidative •OH production and antioxidant GSH depletion
Ferroptosis↑, ferroptosis-dependent ICD response in cancer cells
selectivity↑, Markedly decreased cytotoxicity against the normal cell line, 293T, was seen
GSH/GSSG↓, GSH/GSSH ratio decreased from ∼9.30 to ∼4.71 after treatment with Cu-1 at its IC50 concentration over the course of 12 h
*ROS∅, only a slight increase was observed in (normal) 293T
eff↑, In sharp contrast, Cu-1 demonstrated a greater in vivo antitumor effect compared to oxaliplatin (Fig. 6 B and D) and did not induce systemic toxicity or body weight loss

1615- EA,    Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers
- Human, Nor, NA
*BioAv∅, 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h.
*ROS∅, whereas the generation of reactive oxygen species (ROS) was not affected

2851- FIS,    Apoptosis induction in breast cancer cell lines by the dietary flavonoid fisetin
- in-vitro, BC, MDA-MB-468 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, BC, T47D - in-vitro, BC, SkBr3 - in-vitro, Nor, NA
tumCV↓, Fisetin exhibited a dose- and time-dependent cytotoxic effect on breast cancer cell lines (e.g., 100 µM fisetin decreased MDA-MB-468 cell viability by 70% at 72h
selectivity↑, In contrast, the viability of normal cells was not substantially affected by concentrations of fisetin that killed breast cancer cells.
TumCCA↑, Fisetin-treated breast cancer cells showed cell cycle arrest (MDA-MB-468 cells arrested at G2/M phase; MDA-MB-231 cells arrested in S-phase) and death by apoptosis
Apoptosis↑,
ROS∅, fisetin did not cause ROS production in MDA-MB-468 or 231 cells, indicating that ROS do not contribute to the cytotoxic effect of fisetin

850- Gra,    Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by Annona muricata L. bark extract and phytochemical, annonacin
- in-vitro, PC, PC3 - in-vitro, Pca, DU145
ROS∅, EAB extract and annonacin does not elicit ROS generation in DU-145 cells
MMP∅,
Casp3↑, suggesting a caspase independent cell death
Casp7↑,
VEGF↓,

187- MFrot,  MF,    Method for noninvasive whole-body stimulation with spinning oscillating magnetic fields and its safety in mice
- in-vivo, GBM, NA
selectivity↑, Our in vitro experiments demonstrated selective cancer cell death while sparing normal cells by sOMF-induced increase in intracellular reactive oxygen species (ROS) levels due to magnetic perturbation of mitochondrial electron transport.
ROS↑,
*ROS∅,
*toxicity∅, no significant adverse effects of chronic or acute sOMF stimulation on the health, behavior, electrocardiographic and electroencephalographic activities, hematologic profile, and brain and other tissue and organ morphology of treated mice
ETC↓, We have evidence that its mechanism of action involves alteration of electron transport in the mitochondrial respiratory chain leading to the production of reactive oxygen species (ROS)(
TumVol↓, In a case report published recently we reported that 36-day treatment with this device caused a > 30% shrinkage of the contrast-enhanced tumor volume of a left frontal GBM in a 53-year-old male patient
Dose↝, rrangement of oncoscillators generates a magnetic field strength of >1 mT (range 1 – ~100 mT) in each cage

2046- PB,    Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-468 - in-vitro, Nor, MCF10
Apoptosis↑, NaBu induced a dose and time-dependent cell toxicity in breast cancer cells which was related to the cell cycle arrest and induction of apoptosis.
i-ROS?, NaBu-elicited apoptosis was accompanied by the elevated level of ROS
Casp↑, increased caspase activity
MMP?, reduced mitochondrial membrane potential (Δψm) in MCF-7 and MDA-MB-468 cells
selectivity↑, and with no effect on the above mentioned factors in MCF-10A cells.
*ROS∅, however the level of ROS production was remained approximately unchanged in MCF-10A cells.
HDAC↓, Sodium butyrate (NaBu), one of the well-studied HDACi, is a short-chain fatty acid and the byproduct of carbohydrate metabolism in the gut
DNArepair↓, Sodium butyrate including the inhibition of DNA double strand break repair and stress oxidative
Casp3↑, effect of sodium butyrate on the cell cycle distribution, intracellular formation of Reactive oxygen species (ROS), the caspase 3 and 8 activity,
Casp8↑,
*toxicity↓, MCF-10A cells were treated with the same concentrations of sodium butyrate (0.1–20 mM) for 24, 48, 72 h and the subsequent cytotoxic effect was significantly lower comparing to the breast cancer cells.
TumCCA↑, significant elevation in the percentage of accumulated cells in the sub-G1 phase which was observed in MCF-7 and MDA-MB-468 cells however the effect of sodium butyrate on MCF-10A cell cycle distribution was inconsiderable

2941- PL,    Selective killing of cancer cells by a small molecule targeting the stress response to ROS
- in-vivo, BC, MDA-MB-231 - in-vitro, OS, U2OS - in-vitro, BC, MDA-MB-453
ROS↑, . Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death
Apoptosis↑,
selectivity↑, but it has little effect on either rapidly or slowly dividing primary normal cells
*ROS∅, In contrast, PL did not cause an increase in ROS levels in normal cells
GSH↓, lead to a decrease in GSH and an increase in GSSG levels in cancer cells
GSSG↑,
H2O2↑, we found that hydrogen peroxide and nitric oxide, but not superoxide anion, were among the ROS species induced by PL in cancer cells
NO↑,
Half-Life?, 0.8 hrs

2955- PL,    Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine
- in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
ROS?, Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells.
*ROS∅,
other⇅, opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1)
HO-1↑, Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells.
*HO-1↑,
NRF2↑, piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species.
Keap1↓, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1)
cl‑PARP↑, Following piperlongumine treatment, cleaved PARP levels increased in time- (Fig. 1D) and dose-dependent
selectivity↑, These data clearly show that piperlongumine has a cancer cell-selective killing effect
GSH↓, piperlongumine can selectively decrease the level of reduced GSH and increase the level of oxidized GSSG, leading to ROS accumulation and subsequent apoptosis in cancer cells
GSSG↑, we observed piperlongumine-mediated depletion of GSH, a reduction in the GSH/GSSG ratio and accumulation of intracellular ROS in MCF-7 cells but not in MCF-10A cells

1987- PTL,  Rad,    A NADPH oxidase dependent redox signaling pathway mediates the selective radiosensitization effect of parthenolide in prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Nor, PrEC
selectivity↑, parthenolide (PN), a sesquiterpene lactone, selectively exhibits a radiosensitization effect on prostate cancer PC3 cells but not on normal prostate epithelial PrEC cells.
RadioS↑,
ROS↑, oxidative stress in PC3 cells but not in PrEC cells
*ROS∅, oxidative stress in PC3 cells but not in PrEC cells
NADPH↑, In PC3 but not PrEC cells, PN activates NADPH oxidase leading to a decrease in the level of reduced thioredoxin, activation of PI3K/Akt and consequent FOXO3a phosphorylation, which results in the downregulation of FOXO3a targets, MnSOD, CAT
Trx↓,
PI3K↑,
Akt↑,
p‑FOXO3↓, downregulation of FOXO3a targets, antioxidant enzyme manganese superoxide dismutase (MnSOD) and catalase
SOD2↓, MnSOD
Catalase↓,
radioP↑, when combined with radiation, PN further increases ROS levels in PC3 cells, while it decreases radiation-induced oxidative stress in PrEC cells
*NADPH∅, Parthenolide activates NADPH oxidase in PC3 cells but not in PrEC cells
*GSH↑, increases glutathione (GSH) in PrEC cells(normal cells)
*GSH/GSSG↑, GSH/GSSG ratio is not significantly changed by parthenolide in PC3 cells but is increased 2.4 fold in PrEC cells (normal cells)
*NRF2↑, The induction of GSH may be due to the activation of the Nrf2/ARE (antioxidant/electrophile response element) pathway

68- QC,  BaP,    Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PrEC
PrxI∅, Prx-I, Prx-II PrEC cells
PrxII∅, PrEC cells
*toxicity↓, lack of quercetin-mediated changes in Prx expression suggests that quercetin does not interfere with H2O2 levels, and thus may have no deleterious effect in normal prostate cells
ROS↓, <10uM Quercetin
ROS↑, BaP-mediated toxicity in both 22Rv1 and PrEC cells was confirmed by a significant increase in reactive oxygen species
ROS∅, Quercetin also antagonized the increase in ROS by BaP which suggests that BaP-mediated oxidative stress could be blocked with quercetin in 22Rv1 and PrEC cells. S
chemoP↑, Studies have shown that quercetin can be a potential chemopreventative agent in prostate cancer.
PrxII↑, A physiologically achievable concentration (5uM) of quercetin increased the expression of Prx II without affecting the Prx I levels in 22Rv1 cells
i-H2O2↓, Upregulation of Prx II may reduce the intracellular levels of H 2 O2 which in turn can interfere with growth signaling pathways suppressing cell proliferation.

980- QC,    Dietary Quercetin Exacerbates the Development of Estrogen-Induced Breast Tumors in Female ACI Rats
- in-vivo, BC, NA
COMT↓, bad
ROS∅, quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E2-induced oxidant stress and may exacerbate breast carcinogenesis in E2-treated ACI rats.

4570- RF,    Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems
- Review, Nor, NA
*ETC↓, Numerous studies revealed the detrimental effects of EMFs from mobile phones, laptops, and other electric devices on sperm quality and provide evidence for extensive electron leakage from the mitochondrial electron transport chain
*ROS↑, a growing body of evidence suggests that EMF exposure during spermatogenesis induces increased ROS production associated with decreased ROS scavenging activity.
*ROS∅, Similarly, numerous authors did not find the increase in ROS levels described above

3950- Taur,    Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes
- Review, Diabetic, NA - Review, Stroke, NA - Review, AD, NA
*Ca+2↝, taurine homeostasis can impact a number of biological processes, such as osmolarity control, calcium homeostasis, and inhibitory neurotransmission, and have been reported in both metabolic and neurodegenerative disorders.
*neuroP↑, taurine can afford neuroprotection in individuals with obesity and diabetes.
*other↝, Notably, both methionine and cysteine produced from protein degradation can generate taurine as an end-product
*pH↝, Taurine might counteract extreme mitochondrial pH fluctuations and help preserve mitochondrial physiology.
*ROS∅, Taurine is not able to act as a radical scavenger
eff↑, Taurine also decreased the activity of glutathione peroxidase and manganese-superoxide dismutase upon tamoxifen toxicity, which contributed to decreasing mitochondrial oxidative stress, measured through lipid peroxidation, protein carbonyl content, a
*MMP↑, In sum, taurine supplementation is proposed to improve the function of the mitochondria, contributing to the preservation of mitochondrial membrane potential, proton gradient, and matrix pH that are critical for energy metabolism and efficient oxidat
*Apoptosis↓, Taurine was found to prevent apoptosis upon many noxious challenges
*other↝, The most striking neuroprotective effects of taurine were observed on the reduction of apoptotic rates and the improvement of neurological outcomes upon brain ischemia.
*ER Stress↓, prevention of mitochondrial and endoplasmic reticulum (ER) stress.
*Bcl-xL↓, reduction of anti-apoptotic Bcl-xL and the increase of the pro-apoptotic Bax, preventing cytochrome C release from the mitochondria, and inhibiting the activation of calpain and caspase-3
*BAX↑,
*Cyt‑c↑,
*cal2↓,
*Casp3↓,
*UPR↓, prevent ischemia/hypoxia-induced endoplasmic reticulum (ER) stress by inhibiting the unfolded protein response via transcription factor 6 (ATF6), protein kinase R-like ER kinase (PERK), and inositol-requiring enzyme 1 (IRE1) pathways
*other↝, Altogether, one might speculate that taurine loss in patients with AD is linked to worsened cognitive deterioration.
*NF-kB↓, ameliorated the diabetes-induced increase of the transcription factor NF-κβ, involved in inflammatory processes, and the diabetes-induced reduction of Nrf2 and glucose transporters Glut1 and Glut3 in the brain.
*NRF2↑,
*GLUT1↑,
*GLUT3↑,
*memory↑, In mice fed a fat-rich diet, which develop metabolic syndrome, we recently demonstrated that 3% (w/v) taurine supplemented in the drinking water for 2 months prevented memory impairment

1888- VitB1/Thiamine,  DCA,    High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate
- in-vitro, PC, SK-N-BE - NA, PC, PANC1
p‑PDH↓, Both thiamine and DCA reduced the extent of PDH phosphorylation, reduced glucose consumption, lactate production, and mitochondrial membrane potential.
GlucoseCon↓, High dose thiamine reduces glucose consumption and lactate production
lactateProd↓,
MMP↓,
Casp3↑, High dose thiamine and DCA did not increase ROS but increased caspase-3 activity
eff↑, Our findings suggest that high dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate
PDKs↓,
selectivity↑, An advantage to targeting PDK activity is that overexpression of PDKs and extensive phosphorylation of PDH is found in cancer cells and not in normal tissue [14]. This may provide for selective targeting towards malignant tissue
TumCG↓, thiamine suppressed tumor growth at doses greater than 75 times the recommended daily intake
Dose∅, IC50 of thiamine was lower than DCA for both cell lines with values of 4.9 for SK-N-BE and 5.4 mM for Panc-1.
MMP↓, decrease in mitochondrial membrane potential
ROS∅, cells treated with thiamine or DCA were assayed for peroxide following 30 min, 1 h, and 2 h of treatment. No significant change in ROS was observed over all time
toxicity↑, Smithline et al. reported no adverse effects in healthy patients who were given 1.5g/day of thiamine [34]. Only minor side effects, such as nausea and indigestion were reported in patients given doses as high as 7.5 g/day
antiOx↑, Free thiamine has direct antioxidant properties


Showing Research Papers: 1 to 32 of 32

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 32

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↓, 2,   compI↓, 1,   Ferroptosis↑, 1,   GPx↓, 1,   GPx↑, 1,   GSH↓, 4,   GSH/GSSG↓, 2,   GSSG↑, 2,   H2O2↑, 1,   i-H2O2↓, 1,   HO-1↑, 1,   Keap1↓, 1,   NRF2↓, 1,   NRF2↑, 2,   OXPHOS↓, 2,   Prx6↑, 1,   PrxI∅, 1,   PrxII↑, 1,   PrxII∅, 1,   ROS?, 1,   ROS↓, 2,   ROS↑, 16,   ROS↝, 1,   ROS∅, 9,   i-ROS?, 1,   mt-ROS↑, 1,   SOD↓, 2,   SOD↑, 1,   SOD2↓, 1,   Trx↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   ATP∅, 1,   CDC25↓, 1,   compIII↓, 1,   compIII↑, 1,   ETC↓, 1,   mitResp↓, 1,   MMP?, 1,   MMP↓, 8,   MMP∅, 1,   mtDam↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,   cMyc↓, 1,   GlucoseCon↓, 1,   lactateProd↓, 1,   NADPH↑, 1,   p‑PDH↓, 1,   PDKs↓, 1,  

Cell Death ⓘ

Akt↑, 1,   p‑Akt↓, 2,   Apoptosis↑, 8,   Bak↑, 1,   BAX↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp↑, 2,   Casp3?, 1,   Casp3↑, 6,   proCasp3↑, 1,   Casp7↑, 1,   Casp8↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 2,   Ferroptosis↑, 1,   IAP1↓, 1,   JNK↑, 2,   MAPK↑, 1,   p‑p38↓, 1,   Paraptosis↑, 1,   survivin↓, 3,   TRPV1↑, 1,   TumCD↑, 3,  

Transcription & Epigenetics ⓘ

other↓, 1,   other⇅, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 3,   HSP70/HSPA5↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   DNArepair↓, 1,   P53↓, 1,   P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 4,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↑, 1,   CDK2↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

cFos↑, 1,   CSCs↓, 1,   FOXO↑, 1,   p‑FOXO3↓, 1,   HDAC↓, 1,   NOTCH1↓, 1,   PI3K↑, 1,   STAT3↓, 1,   TumCG?, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   ER-α36↓, 1,   MMP2↓, 1,   MMP9↓, 1,   Slug↓, 1,   Snail↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumCP⇅, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   NO↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↓, 1,   IL6↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

COMT↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 2,   ChemoSen∅, 1,   Dose⇅, 1,   Dose↝, 3,   Dose∅, 1,   eff↓, 2,   eff↑, 5,   Half-Life?, 1,   RadioS↑, 3,   selectivity↑, 21,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 2,   chemoP↑, 3,   neuroP↑, 1,   radioP↑, 1,   RenoP↑, 1,   toxicity↑, 1,   TumVol↓, 1,  
Total Targets: 142

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 1,   GSH/GSSG↑, 1,   HO-1↑, 1,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 1,   ROS∅, 24,   SOD2↑, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

ETC↓, 1,   MMP↑, 1,   MMP∅, 1,  

Core Metabolism/Glycolysis ⓘ

CRM↑, 1,   NADPH∅, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↑, 1,   Bcl-xL↓, 1,   Casp3↓, 1,   Cyt‑c↑, 1,  

Transcription & Epigenetics ⓘ

other↝, 3,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   UPR↓, 1,  

Migration ⓘ

Ca+2↝, 1,   cal2↓, 1,  

Barriers & Transport ⓘ

GLUT1↑, 1,   GLUT3↑, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Cellular Microenvironment ⓘ

pH↝, 1,  

Drug Metabolism & Resistance ⓘ

BioAv∅, 1,  

Functional Outcomes ⓘ

memory↑, 1,   neuroP↑, 1,   toxicity↓, 5,   toxicity∅, 3,  
Total Targets: 34

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
4 Ashwagandha(Withaferin A)
3 Baicalein
2 Capsaicin
2 Piperlongumine
2 Quercetin
1 Silver-NanoParticles
1 Allicin (mainly Garlic)
1 Apigenin (mainly Parsley)
1 doxorubicin
1 Artemisinin
1 Astaxanthin
1 Berberine
1 Betulinic acid
1 brusatol
1 Chrysin
1 Copper and Cu NanoParticles
1 Ellagic acid
1 Fisetin
1 Graviola
1 Magnetic Field Rotating
1 Magnetic Fields
1 Phenylbutyrate
1 Parthenolide
1 Radiotherapy/Radiation
1 benzo(a)pyrene
1 EMF
1 Taurine
1 Vitamin B1/Thiamine
1 Dichloroacetate
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

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