OXPHOS Cancer Research Results

OXPHOS, Oxidative phosphorylation: Click to Expand ⟱

Source:

Type:

Oxidative phosphorylation (or phosphorylation) is the fourth and final step in cellular respiration.
Alterations in phosphorylation pathways result in serious outcomes in cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers.
Many tumors exhibit a well-known metabolic shift known as the Warburg effect, where glycolysis is favored over OxPhos even in the presence of oxygen. However, this is not universal.
Many cancers, including certain subpopulations like cancer stem cells, still rely on OXPHOS for energy production, biosynthesis, and survival.

– In several cancers, especially during metastasis or in tumors with high metabolic plasticity, OxPhos can remain active or even be upregulated to meet energy demands.

In some cancers, high OxPhos activity correlates with aggressive features, resistance to standard therapies, and poor outcomes, particularly when tumor cells exploit mitochondrial metabolism for survival and metastasis.

– Conversely, low OxPhos activity can be associated with a reliance on glycolysis, which is also linked with rapid tumor growth and certain adverse prognostic features.

Inhibiting oxidative phosphorylation is not a universal strategy against all cancers. Targeting OXPHOS can potentially disrupt the metabolic flexibility of cancer cells, leading to their death or making them more susceptible to other treatments.
Since normal cells also rely on OXPHOS, inhibitors must be carefully targeted to avoid significant toxicity to healthy tissues.
Not all tumors are the same. Some may be more glycolytic, while others depend more on mitochondrial metabolism. Therefore, metabolic profiling of tumors is crucial before adopting this strategy. Inhibiting OXPHOS is being explored in combination with other treatments (such as chemo- or immunotherapies) to improve efficacy and overcome resistance.

In cancer cells, metabolic reprogramming is a hallmark where cells often rely on glycolysis (known as the Warburg effect); however, many cancer types also depend on OXPHOS for energy production and survival. Targeting OXPHOS(using inhibitor) to increase the production of reactive oxygen species (ROS) can selectively induce oxidative stress and cell death in cancer cells.

-One side effect of increased OXPHOS is the production of reactive oxygen species (ROS).
-Many cancer cells therefore simultaneously upregulate antioxidant systems to mitigate the damaging effects of elevated ROS.
-Increase in oxidative phosphorylation can inhibit cancer growth.

Scientific Papers found: Click to Expand⟱

3453-

5-ALA,

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

in-vitro,

Lung,

A549

OXPHOS↑, A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption.
OCR↑,
Warburg↓, These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death.
ROS↑, ALA significantly increased O2-generation over 4 h
SOD2↑, ALA stimulates MnSOD, catalase and HO-1 protein expression.
Catalase↑,
HO-1↑,
Casp3↑, ALA induced an increase in the protein expression of activated (cleaved) caspase-3.
Apoptosis↑, these data demonstrate that ALA induced caspase- dependent apoptosis in A549 cells.

5689-

BJ,

Brucea javanica oil inhibited the proliferation, migration, and invasion of oral squamous carcinoma by regulated the MTFR2 pathway

vitro+vivo,

Oral,

CAL27

nude mice with xenografted OSCC cells and in vitro experiments with OSCC

TumCP↓, BJO treatment significantly inhibited the proliferation, migration, and invasiveness of OSCC cells
TumCMig↓,
TumCI↓,
SOD2↓, BJO could effectively reduce the expression levels of MTFR2 and SOD2/H2O2 related signal transduction pathways.
H2O2↓,
OXPHOS↑, At the same time, the expression of oxidative phosphorylation markers increased, the expression of glycolytic markers decreased
Glycolysis↓, down-regulation of MTFR2-mediated aerobic glycolysis
ROS↑, Wang D et al. suggested that Brucea javanica oil induces cell cycle arrest and apoptosis in lung cancer cells through reactive oxygen species (ROS)-mediated mitochondrial dysfunction (14).
RadioS↑, Pan P et al. reported that Brucea javanica oil enhances the radio-sensitization of esophageal cancer cells by inhibiting HIF1α (15).
Hif1a↓,
TumCG↓, BJO represses the xenograft tumor growth in vivo

933-

CUR,

EP,

Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: A global proteomics study

in-vitro,

BC,

50uM, 1200v/c,100us

Apoptosis↑,
ALDOA↓,
ENO2↓,
LDHA↓, LDH inhibitor
LDHB↓,
PFKP↓,
PGK1↓,
PGM1↓,
PGAM1↓,
OXPHOS↑, upregulation of 10 oxidative phosphorylation pathway proteins
TCA↑, upregulation of 8 tricarboxylic acid (TCA) cycle proteins

1875-

DCA,

Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells

in-vitro,

neuroblastoma,

in-vivo,

NA,

five mice were treated with 2.5 mg/kg/
dose of DCA, 14 mice were treated with 25 mg/kg/dose

mice

selectivity↑, acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells.
AntiCan↑, DCA exhibits an unexpected anticancer effect on NB tumor cells
TumVol↓, growth inhibition became statistically significant when mice were treated with 25 mg/kg/dose of DCA (55% of reduction compared with control group)
PDKs↓, effects of DCA are related to PDK inhibition, mitochondrial oxidative phosphorylation activation and specific mitochondrial hyperpolarization reduction,
mt-OXPHOS↑,
MMP↓,
Glycolysis↓, shifting cellular metabolism from glycolysis to glucose oxidation, without any deleterious effect on normal cells.
toxicity↓, Indeed, more than 40 clinical trials of DCA report that the most significant adverse effect of long-term DCA administration is a reversible peripherical neuropathy.
Warburg↓, indeed, DCA is able to reverse the Warburg effect by inhibiting PDK, restoring mitochondrial membrane potential and increasing ROS production.
ROS↑,
eff↑, DCA was celebrated as the magic bullet against cancer, even if it is currently not yet approved for cancer treatment.

5196-

DCA,

Dichloroacetate induces apoptosis in endometrial cancer cells

in-vitro,

Var,

selectivity↑, Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells.
MMP↓, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism.
survivin↓,
Ca+2↓, DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway.
P53↑, DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism.
PDK1↓, DCA binds to PDK and attenuates inhibition of PDH activity.
PDH↑,
Glycolysis↓, The increased PDH activity shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential (MMP) hyperpolarization
OXPHOS↑,
ROS↑, translocation of reactive oxygen species (ROS) and cytochrome c from the mitochondria to the cytoplasm, subsequently inducing apoptosis through the activation of caspases
Cyt‑c↑,
Apoptosis↑,
Casp↑,
tumCV↓, DCA Reduces Endometrial Cancer Cell Viability in a Dose-Dependent Manner
PUMA↑, DCA Increases PUMA Expression

4901-

DCA,

Sal,

Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer

Review,

NSCLC,

Glycolysis↓, DCA redirects mitochondrial metabolism away from glycolysis to OXPHOS by the inhibition of PDKs
OXPHOS↑,
PDKs↓,
ROS↑, DCA increases reactive oxygen species (ROS), which induce downstream changes in mitochondrial function, causing the selective apoptosis of cancer cells.
Apoptosis↑,
GlucoseCon↓, treatment with DCA decreased glucose consumption and lactate production in vitro in a manner that was statistically significant compared to the controls
lactateProd↓,
RadioS↑, it enhanced the sensitivity of A549 and H1299 cells to X-ray-induced cell killing
TumAuto↑, DCA has been shown to induce autophagy instead of inhibiting it.
mTOR↓, The DCA-induced induction of autophagy was found to be mediated by the generation of ROS, the inhibition of the mammalian targets of rapamycin (mTOR),
LC3s↓, Lu and colleagues found that LC3 decreased while p62 levels increased, both of which are hallmarks of autophagy inhibition
p62↑,
TumCG↓, In vivo studies have demonstrated that DCA inhibits the growth of A549 and H1975 tumor xenografts and enhances the survival of tumor-bearing nude mice
OS↑,
toxicity↝, the most clinically limiting side effect of DCA is peripheral neuropathy
ChemoSen↑, DCA exerts synergistic potential with the most widely used chemotherapy agent, paclitaxel, on NSCLC cells.
eff↑, DCA has also been shown to have anticancer synergies with various non-traditional agents, the most prominent of which is metformin.
eff↑, Another compound that DCA has been shown to have a strong synergism with is ivermectin.
Ferritin↓, SAL and its derivatives prevent the movement of iron from the lumen to the cytosol, triggering an iron-depletion reaction that is characterized by the rapid degradation of ferritin
CSCs↓, SAL has been shown to selectively target CSCs in vitro and in vivo, but its mode of action is not fully understood.
EMT↓, SAL has also been shown to suppress the epithelial–mesenchymal transition (EMT) as well as transforming growth factors (TGFs). EMT is a process that is pivotal to metastasis.
ROS↑, SAL triggers apoptosis by elevating intracellular ROS levels, leading to the translocation of Bax protein to the mitochondria, cytochrome c (Cytc) release, and the activation of caspase-3
Cyt‑c↑,
Casp3↑,
ER Stress↑, SAL was observed to upregulate ER stress-related proteins in a time-/dose-dependent manner
selectivity↑, SAL induced cell death in multiple apoptosis-resistant cancer cell lines, but not in normal healthy human cells
eff↑, Skeberdytė and colleagues were among the first to recognize that DCA had synergistic potential with SAL.
TumCG↓, DCA and SAL were found to significantly suppress tumor growth in vivo in the mice.

1863-

dietFMD,

Chemo,

Effect of fasting on cancer: A narrative review of scientific evidence

Review,

Var,

eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

1853-

dietFMD,

Impact of Fasting on Patients With Cancer: An Integrative Review

Review,

Var,

*toxicity∅, Data suggest overall good compliance, no malnutrition, minimal side effects. No significant changes were identified to suggest increased harm.
QoL∅, unchanged quality of life (QOL),
eff↑, improved endocrine parameters
eff↝, mixed results for cancer outcomes
ChemoSideEff↓, decreasing chemotherapy-related side effects
TumCG↓, limiting tumor growth
Dose↑, When fasting is used as an adjunct to chemotherapy, a minimum fasting period of at least 48 hours is currently recommended for nutritional interventions in order to achieve a measurable metabolic response at the cellular level
toxicity↝, The increased risk for poor outcomes associated with malnutrition, weight loss, and cachexia poses an obvious safety concern for patients with cancer who participate in calorie-restricted fasting
eff↑, short-term fasting involving water-only or limited daily calorie consumption for less than a week has the potential to achieve positive metabolic changes while avoiding malnutrition and significant weight loss
IGF-1↑, statistically significant decrease in IGF-1 among participants compliant with fasting compared with regular diet during the middle of therapy
*OXPHOS↑, Healthy cells also use mitochondrial oxidative phosphorylation for metabolism while cancer cells use aerobic glycolysis, also known as the Warburg effect
BG↓, statistically significant decrease in glucose among participants compliant with fasting compared with controls
Insulin↓, statistically significant decrease in insulin among participants compliant with fasting compared with regular diet before the first cycle of chemotherapy (p = .001), as well as during the middle of therapy
RadioS↑, A complete or partial radiographic response was also noted more often among fasting participants compared with normal diet participants

5069-

dietSTF,

The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases

Review,

Var,

Risk↓, IF has shown potential for reducing cancer risk and enhancing therapeutic efficacy by sensitizing tumor cells to chemotherapy and radiotherapy.
ChemoSen↑, intermittent fasting (IF) may enhance the effectiveness of chemotherapy and targeted therapies by activating autophagy. IF enhances the effectiveness of chemotherapy, including drugs such as cisplatin, cyclophosphamide, and doxorubicin
RadioS↑, disease stabilization, improved response to radiotherapy patients with glioma
*Dose↝, 16:8—16 h of fasting with an 8 h eating window;
*Dose↝, 5:2—consuming a standard number of calories for 5 days and reducing intake to 25% of daily requirements for 2 days;
*Dose↝, Eat–Stop–Eat—complete fasting for 24–48 h.
*LDL↓, IF during Ramadan (approximately 18 h of fasting for 29–30 days) reduces LDL cholesterol levels and increases HDL cholesterol in women, as well as reducing inflammatory markers such as CRP and TNF-α
*CRP↓,
*TNF-α↓,
TumAuto↓, Intermittent fasting activates autophagy as an adaptive mechanism to nutrient deprivation, which may modulate tumor development and treatment
GLUT1↓, fasting reduces the expression of glucose transporters GLUT1/2, which slow down cancer metabolism and increase the susceptibility of cancer cells to oxidative stress
GLUT2↓,
glucose↓, studies on cell and animal models have shown that intermittent fasting reduces glucose and insulin-like growth factor (IGF-1) levels [103], as well as insulin [104,105], resulting in the inhibition of the mTOR kinase pathway (PI3K/Akt/mTOR), suppress
IGF-1↓,
Insulin↓,
mTOR↓,
mTORC1↓, suppression of mTORC1 [22], and activation of AMPK through increased ADP/ATP ratio in cells, which supports autophagy and induces apoptosis
AMPK↑,
Warburg↓, Moreover, IF counteracts the Warburg effect by promoting oxidative phosphorylation, leading to an increase in the production of reactive oxygen species (ROS) and enhanced oxidative stress in cancer cells [106,108], causing DNA damage and the activati
OXPHOS↑,
ROS↑,
DNAdam↑,
JAK1↓, fasting reduces the production of adenosine by cancer cells, inhibiting the activation of the JAK1/STAT pathway, thereby reducing cancer cell proliferation
STAT↓,
TumCP↓,
QoL↑, reduction in IGF-1 levels, improved quality of life patients with multiple cancer types

2512-

H2,

Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch

in-vivo,

asthmatic,

selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

2887-

HNK,

Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming

in-vitro,

AD,

BV2

*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
*ATP↑,
*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
*MMP↑,
*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
*PGC-1α↑,

2543-

M-Blu,

The use of methylene blue to control the tumor oxygenation level

in-vivo,

Lung,

 mouse Lewis lung carcinoma (LLC) model

OCR↑, A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50–75 mm3) and normal tissue 120 min after the introduction of MB
OXPHOS↑, A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB
Half-Life↝, persisted for at least 120 min after the administration and did not return to its initial level.
AntiTum↑, B therapy enhances tumor oxygenation levels, which contributes to more effective antitumor therapy.

2541-

M-Blu,

Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism

in-vivo,

Var,

 mice model of Ehrlich carcinoma

TumCG↓, In the group receiving MB with drinking water, a decrease of the tumor growth rate, reduction of oxygenation level, and a1/a2 metabolic index were observed, which confirms the shift from glycolysis to oxidative phosphorylation.
Glycolysis↓,
OXPHOS↑,
ROS↑, The ability of MB to generate reactive oxygen species together with a small molecular size makes this dye attractive for using it as a photosensitizer in photodynamic therapy
OCR↑, MB can increase oxygen consumption, decrease glycolysis and increase glucose uptake in vitro
GlucoseCon↑,
lactateProd↓, The decrease of the lactate amount and extracellular acidification rate after MB introduction, which is reported in the literature [31], is supposed to be a secondary effect mediated by the metabolic shift towards oxidation phosphorylation as a resul

2540-

M-Blu,

Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots

Review,

Var,

Review,

AD,

*OCR↑, MB was found to increase oxygen consumption of normal tissues having aerobic glycolysis and of tumors
*Glycolysis↓, Methylene blue increases oxygen consumption, decrease glycolysis, and increases glucose uptake in vitro.
*GlucoseCon↑, Methylene blue enhances glucose uptake and regional cerebral blood flow in rats upon acute treatment.
neuroP↑, methylene blue provides protective effect in neuron and astrocyte against various insults in vitro and in rodent models of Alzheimer’s, Parkinson’s, and Huntington’s disease.
Warburg↓, In glioblastoma cells, methylene blue reverses Warburg effect by enhancing mitochondrial oxidative phosphorylation, arrests glioma cell cycle at s-phase, and inhibits glioma cell proliferation.
mt-OXPHOS↑,
TumCCA↑,
TumCP↓,
ROS⇅, MB has very unique redox property that exists in equilibrium between oxidized state in dark blue (MB) and colorless reduced state (leucomethylene blue), making it both prooxidant and antioxidant under different conditions.
*cognitive↑, Methylene blue feeding improved water-maze and bridge walking performance in 5 X FAD mice. MB enhances memory function in normal rodents potentially through neurometabolic mechanisms
*mTOR↓, MB has been demonstrated to induce autophagy and attenuate tauopathy through inhibition of mTOR signaling both in vitro and in vivo
*mt-antiOx↑, Secondly, the distinct redox property enables MB as a regenerable anti-oxidant in mitochondria that distinct from the traditional free radical scavenges
*memory↑, , MB has been found to improve various experimental memory tasks in rodents
*BBB↑, MB can cross BBB and reach brain at concentrations 10 times higher than that in the circulation
*eff↝, In fibroblast cells, MB has been shown to stimulate 2-deoxyglucose uptake (Louters et al., 2006; Roelofs et al., 2006). Using MRI and PET, we demonstrated that acute treatment of MB significantly enhance glucose uptake
*ECAR↓, MB increased oxygen consumption rate and decreased extracellular acidification rate in both neuronal cells and astrocytes
eff↑, MB has also been used as a tracer for cancer diagnosis and as a photosensitizer for cancer treatment
lactateProd↓, MB increase oxygen consumption rate, decrease lactic acid production and extracellular acidification rate, reduce NADPH, and inhibit proliferation
NADPH↓,
OXPHOS↑, increases oxidative phosphorylation, decreases glycolytic flux and metabolic intermediates, hence, exhausts the building brick for cancer cell proliferation.
AMPK↑, MB is capable of activating AMPK signal pathway
selectivity↑, with low toxicity, and the high affinity to both neuronal and cancer tissues

2384-

MET,

Integration of metabolomics and transcriptomics reveals metformin suppresses thyroid cancer progression via inhibiting glycolysis and restraining DNA replication

in-vitro,

Thyroid,

BCPAP

BCPAP cell lines were treated with 10 and 20 mM metformin for 24 h in subsequent experiments

in-vivo,

NA,

nude mice

in-vitro,

Thyroid,

TPC-1

Glycolysis↓, Metformin promotes the metabolic transition from glycolysis to oxidative phosphorylation.
OXPHOS↑,
tumCV↓, metformin reduced cell viability, invasion, migration, and EMT, and induced apoptosis and cell cycle G1 phase arrest in thyroid cancer.
TumCI↓,
TumCMig↓,
EMT↓,
Apoptosis↑,
TumCCA↑, cell cycle G1 phase
LDHA↓, metformin suppressed glycolysis by downregulating the key glycolytic enzymes LDHA and PKM2 and upregulating IDH1 expression in thyroid cancer.
PKM2↓,
IDH1↑,
TumCG↓, Metformin inhibits the growth of thyroid cancer in vivo

2242-

MF,

Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair

in-vitro,

Nor,

2.5G, 5G, 10G, 15G, and 20G

*MMP↑, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation.
*Diff↑,
*OXPHOS↑, effect was mediated via increased OxPhos activity
*BMD↑, EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization
ATP∅, higher mitochondrial OxPhos activity leads to higher ATP production, increased cellular activity leads to increased ATP consumption.

2241-

MF,

Pulsed electromagnetic therapy in cancer treatment: Progress and outlook

Review,

Var,

other↝, PEMFs act on the cell, it will firstly change the cell membrane transport capacity, osmotic potential and ionic valves
p‑ERK↝, Also, it will cause changes in mitochondrial protein profile, decrease mitochondrial phosphor-ERK (extracellular-signal-regulated kinase), p53, and cytochrome c, and activate OxPhos.
P53↝,
Cyt‑c↝,
OXPHOS↑,
Apoptosis↑, PEMFs decreases cellular stress factors, increase energy demand, this series of reactions will eventually lead to apoptosis.
ROS↑, The introduction of PEFs and PEMFs can improve the penetration efficiency of ROS, not only reduce the concentration of drugs, but also reduce the irradiation dose of CAP, w

2247-

MF,

Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis

in-vivo,

Nor,

Sprague Dawley rats

*Glycolysis↓, PEMF-treated animals exhibited decreased glycolysis and increased LDHB expression, enhancing NAD signaling and ATP production
*LDHB↑,
*NAD↑,
*ATP↑,
*antiOx↑, Antioxidant protein levels increased, controlling ROS production.
*ROS↑,
*YAP/TEAD↑, upregulation of YAP and PGC1alpha and increasing slow myosin isoforms, thus speeding up physiological recovery.
*PGC-1α↑,
*TCA↑, increased in PEMF-treated injured limbs
*FAO↑,
*OXPHOS↑, Oxidative phosphorylation was increased in the muscle of injured rats that underwent PEMF treatment

2260-

MF,

Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming

in-vitro,

GBM,

U87MG

18 mT at the center

in-vitro,

GBM,

LN229

in-vivo,

NA,

AMF for 30 min daily, for a total of five sessions.

mice

TumCP↓, proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz.
TumCG↓, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival
OS↑,
ROS↑, This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression.
SOD2↑,
eff↓, anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger.
ECAR↓, decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR).
OCR↑,
selectivity↑, This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Furthermore, in cancer cells, AMF decreased ECAR and increased OCR, while there were no changes in normal cells.
*toxicity∅, did not affect non-cancerous human cells [normal human astrocyte (NHA), human cardiac fibroblast (HCF), human umbilical vein endothelial cells (HUVEC)].
TumVol↓, The results showed a significant treatment effect, as assessed by tumor volume, after conducting AMF treatment five times a week for 2 weeks
PGC-1α↑, Corresponding to the rise in ROS, there was also a time-dependent increase in PGC1α protein expression post-AMF exposure
OXPHOS↑, enhancing mitochondrial oxidative phosphorylation (OXPHOS), leading to increased ROS production
Glycolysis↓, metabolic mode of cancer cells to shift from glycolysis, characteristic of cancer cells, toward OXPHOS, which is more typical of normal cells.
PKM2↓, We extracted proteins that changed commonly in U87 and LN229 cells. Among the individual proteins related to metabolism, pyruvate kinase M2 (PKM2) was found to be inhibited in both.

538-

MF,

The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift

in-vitro,

BC,

MDA-MB-231

in-vitro,

Melanoma,

MSTO-211H

TumCG↓, did not affect the non-malignant counterpart.
Ca+2↑,
COX2↓,
ATP↑, (ATP5B) and mitochondrial transcription (MT-ATP6)
MMP↑, significant enhancement of mitochondrial membrane potential (ΔΨm)
ROS↑, demonstrated for the first time the association of ROS production with the stimulation of the mitochondrial metabolism triggered by the electromagnetic field
OXPHOS↑,
mitResp↑, Mitochondrial respiration is increased by ELF-EMF exposure

2396-

PACs,

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

in-vitro,

HCC,

HCCLM3

80.59 μM

in-vitro,

HCC,

SMMC-7721 cell

76.32 μM

in-vitro,

HCC,

Bel-7402

in-vitro,

HCC,

HUH7

in-vitro,

HCC,

HepG2

in-vitro,

Nor,

L02

TumCP↓, PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro.
TumCCA↓,
Apoptosis↑,
GlucoseCon↓, PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.
lactateProd↓,
PKM2↓,
Glycolysis↓, to suppress aerobic glycolysis
HK2↓, PB2 suppressed the expression of HK2, PFKFB3, and PKM2, while enhancing the expression of OXPHOS in both HCC-LM3 and SMMC-7721 cells
PFK↓,
OXPHOS↑, PB2 inhibited aerobic glycolysis and improved OXPHOS in HCC cell lines
ChemoSen↑, PB2 enhanced the chemosensitivity of SORA on HCC, both in vivo and in vitro
HSP90↓, PB2 reduced the expressions of both HSP90 and HIF-1α in a dose-dependent manner in HCC cells
Hif1a↓,

993-

RES,

Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

in-vitro,

CRC,

Caco-2

10 µM, 48 hr

in-vivo,

Nor,

HCEC 1CT

TumCG↓,
Glycolysis↓,
PPP↓,
ATP↑, significant increase (20%) in ATP production
PDH↑, Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity.
Ca+2↝, resveratrol is a potent modulator of many cellular Ca2+ signaling pathways. Ca2+ is a key mediator of the effect of resveratrol on the oxidative capacity of colon cancer cells.
TumCP↓,
lactateProd↓,
OCR↑, increase of oxygen consumption rate (OCR) both in normal colonic epithelial HCEC 1CT cells
ECAR↓, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells, whereas it was significantly reduced (31%) in HCEC 1CT RPA cells ****
*ECAR∅, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells
*other?, Resveratrol promotes a shift from respiration to glycolysis in cancer-like cells, but not in normal colonocytes
cycE/CCNE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1/CCNA1↑,
TumCCA↑,
cycD1/CCND1↑, and by decreasing cyclin D1
OXPHOS↑, Taken together, these observations indicate that exposure to resveratrol leads to a metabolic reorientation from aerobic glycolysis toward OXPHOS.

3935-

RT,

Sodium rutin ameliorates Alzheimer's disease-like pathology by enhancing microglial amyloid-β clearance

in-vivo,

AD,

*Aβ↓, rutin enhances microglial Aβ clearance, providing a potential therapeutic avenue for Alzheimer’s disease treatment.
*Glycolysis↓, NaR promotes a metabolic switch from anaerobic glycolysis to mitochondrial OXPHOS (oxidative phosphorylation), which could provide microglia with sufficient energy (ATP) for Aβ clearance.
*OXPHOS↑,
*memory↑, eventually reversing spatial learning and memory deficits. Our findings suggest that NaR is a potential therapeutic agent for AD.
*BioAv↓, poor solubility in aqueous media (approximately 0.125 g/liter at room temperature) has largely limited its usage owing to its poor bioavailability
*BioAv↑, In the present study, we processed rutin into sodium salt [hereafter called sodium rutin (NaR)], which is highly water soluble and bioavailable.
*cognitive↑, NaR ameliorates learning and memory deficits and rescues synaptic impairment in mouse models of AD
*Inflam↓, NaR decreases neuroinflammation in AD mice

3194-

SFN,

Sulforaphane impedes mitochondrial reprogramming and histone acetylation in polarizing M1 (LPS) macrophages

in-vitro,

Nor,

*OXPHOS↑, suggesting that OXPHOS activity is needed for maximal inhibition of M1 marker expression by Sfn
*M1↓,
*IL1β↓, Consistent with our previous study [40], presence of Sfn significantly diminished mRNA expression of il1β, il6, nos2, and tnfα in M1 (LPS) cells
*IL6↓,
*NOS2↓,
*TNF-α↓,
*ROS↓, 0 and 10 μM, impaired M1 marker expression, ROS or NO production and preserved respiratory activity after LPS exposure
*NO↓,
*ACC↑, Sfn prevents the drop of nuclear and cytosolic acetyl-CoA in LPS-stimulated macrophages

1001-

SIL,

Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism

in-vitro,

NA,

0–200µM

100µM@72hr

 LMP-1+ NPC tumor cells (C666–1),

TumCG↓,
Glycolysis↓, Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation.
OXPHOS↑,
LDHA↓,
lactateProd↓,
i-citrate↑,
Hif1a↓,
PD-L1↓, silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A

2413-

TTT,

Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression

in-vitro,

GBM,

U87MG

We used [18F]DASA-23, a novel radiotracer that measures PKM2 expression and which has been shown to be safe in humans,

PKM2↓, Quantitative Western blot analysis and qualitative immunofluorescence for PKM2 confirmed the TTFields-induced reduction in PKM2 expression. TTFields exposure reduced PKM2 expression by 49% at 3 d
Glycolysis↓, Regardless, both outcomes suggest a shift from aberrant glycolysis towards oxidative phosphorylation
OXPHOS↑,

Showing Research Papers: 1 to 26 of 26

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 26

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 125

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, mt-antiOx↑, 1, OXPHOS↑, 6, ROS↓, 2, ROS↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 2, MMP↑, 2, OCR↑, 1, PGC-1α↑, 2,

Core Metabolism/Glycolysis ⓘ

ACC↑, 1, ECAR↓, 1, ECAR∅, 1, FAO↑, 1, GlucoseCon↑, 1, Glycolysis↓, 3, Glycolysis↑, 1, LDHB↑, 1, LDL↓, 1, NAD↑, 1, PPARα↑, 1, TCA↑, 1,

Cell Death ⓘ

YAP/TEAD↑, 1,

Transcription & Epigenetics ⓘ

other?, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1, mTOR↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

CRP↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 1, M1↓, 1, TNF-α↓, 2,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1, Dose↝, 3, eff↝, 1,

Clinical Biomarkers ⓘ

BMD↑, 1, CRP↓, 1, IL6↓, 1, NOS2↓, 1,

Functional Outcomes ⓘ

cognitive↑, 2, memory↑, 2, toxicity∅, 2,
Total Targets: 45

Scientific Paper Hit Count for: OXPHOS, Oxidative phosphorylation

5 Magnetic Fields
3 Dichloroacetate
3 Methylene blue
2 diet FMD Fasting Mimicking Diet
1 5-Aminolevulinic acid
1 Brucea javanica
1 Curcumin
1 Electrical Pulses
1 salinomycin
1 Chemotherapy
1 diet Short Term Fasting
1 Hydrogen Gas
1 Honokiol
1 Metformin
1 Proanthocyanidins
1 Resveratrol
1 Rutin
1 Sulforaphane (mainly Broccoli)
1 Silymarin (Milk Thistle) silibinin
1 Tumor Treating Fields

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#:230  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

OXPHOS Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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