OCR Cancer Research Results

OCR, Oxygen consumption rate: Click to Expand ⟱

Source:

Type:

Oxygen consumption rate (OCR) is a measure of the rate at which cells consume oxygen, and it has been found to be altered in cancer cells. Cancer cells often exhibit increased glycolysis, a process in which glucose is converted into energy without the use of oxygen, even in the presence of oxygen. This is known as the Warburg effect.
Cancer cells often exhibit increased glycolysis, which leads to a decrease in OCR.
-When mitochondrial function is impaired (resulting in lower OCR), cells may compensate by upregulating glycolysis to meet their energy needs (known as the Pasteur effect).
-Instruments such as the Seahorse Analyzer allow simultaneous measurement of OCR (reflecting mitochondrial respiration) and Extracellular Acidification Rate (ECAR, which is commonly used as a proxy for glycolysis). This dual measurement helps researchers understand how shifts in one pathway correlate with compensatory changes in the other.

Scientific Papers found: Click to Expand⟱

5275-

3BP,

3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: Introduction to a special issue

Review,

Var,

AntiCan↑, the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent.
HK2↓, reported that HK2 is constitutively overexpressed and that 3BP an inhibitor of this enzyme induces cell death.
OCR↓, this agent was found to inhibit the membrane potential, oxygen consumption, and dehydrogenase activities.

5460-

AF,

Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species

vitro+vivo,

Var,

4T1

RadioS↑, AF at 3–10 μM is a potent radiosensitizer in vitro
ROS↑, . The first one is linked to an oxidative stress, as scavenging of reactive oxygen species (ROS)
eff↓, N-acetyl cysteine counteracted radiosensitization. (NAC)
mt-OCR↓, We also observed a decrease in mitochondrial oxygen consumption with spared oxygen acting as a radiosensitizer under hypoxic conditions.
DNAdam↑, Overall, radiosensitization was accompanied by ROS overproduction, mitochondrial dysfunction, DNA damage and apoptosis
Apoptosis↑,
TrxR↓, targeting thioredoxin reductase (TrxR)
eff↑, a simultaneous disruption of the thioredoxin and glutathione systems by the combination of AF and buthionine sulfoximine was shown to significantly improve tumor radioresponse.

3454-

ALA,

Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness

in-vitro,

BC,

MCF-7

(0.5 mM, 1 mM, 2.5 mM, and 5 mM)

in-vitro,

BC,

MDA-MB-231

TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

2389-

BA,

Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor

in-vitro,

Obesity,

3T3

*ECAR↑, Baicalin promoted metabolic reprogramming in 3T3-L1 preadipocytes, characterized by increased ECAR and decreased OCR
*OCR↓,
*p‑AMPK↑, baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability.
*p‑ACC↑,
*Glycolysis↑, significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism.
*lipidDe↓, inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition.
*SREBP1↓,
*FAO↑, baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO.
*HK2↑, baicalin upregulated glycolytic enzymes, such as HK1, HK2, PKM2, and LDHA, while downregulating pyruvate dehydrogenase,
*PKM2↑,
*LDHA↑,
*PDKs↓,
*ACC↓, leading to decreased acetyl-CoA production and enhanced fatty acid β-oxidation.

2671-

BBR,

Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action

in-vivo,

Diabetic,

*BioAv↓, After oral administration of 20 mg/kg BBR, we were unable to detect BBR in the plasma
*Half-Life↝, In contrast, dhBBR at the same oral dose was rapidly detected in the plasma (Supplementary Fig. 2), displaying a half-life (t1/2) of 3.5 ± 1.3 h and a maximum concentration (Cmax) of 2.8 ± 0.5 ng/ml
*OCR↓, BBR produced a dose-dependent inhibition of oxygen consumption in isolated muscle mitochondria with complex I–linked substrate (pyruvate),
*AMPK↑, ability of BBR to activate AMPK

943-

BetA,

Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

mouse model

Glycolysis↓,
lactateProd↓,
GlucoseCon↓,
ECAR↓,
cMyc↓,
LDHA↓,
p‑PDK1↓,
PDK1↓,
Cav1↑, Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation
*Glycolysis↑, BA could lead to increased glycolysis in mouse embryonic fibroblasts by activating LKB1/AMPK pathway, whereas we found that BA inhibited aerobic glycolysis in breast cancer cells by modulating Cav-1/NF-ÎºB/c-Myc signaling
selectivity↑,
OCR↓, OCR parameters including the basal respiration, maximal respiration and spare respiratory capacity were also simultaneously inhibited
OXPHOS↓, implying that the activity of mitochondrial oxidative phosphorylation (OXPHOS) chain was also suppressed by BA

2733-

BetA,

Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling

in-vitro,

Oral,

12.5–100 μM BA for 24–72 h

in-vivo,

NA,

BA against OSCC in implanted mice in vivo

TumCP↓, BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume.
TumVol↓,
mt-Apoptosis↑, BA significantly promoted mitochondrial apoptosis, as reflected by an increase in TUNEL+ cells and the activities of caspases 3 and 9, an increase in Bax expression, and a decrease in Bcl-2 expression and the mitochondrial oxygen consumption rate.
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↑,
OCR↓, BA dose-dependently decreased the oxygen consumption rate, indicating that BA induced a significant mitochondrial dysfunction
TumCCA↑, BA significantly increased cell population in the G0/G1 phase and decreases the S phase cell number, indicating the occurrence of G0/G1 cell cycle arrest.
ROS↑, ROS generation was significantly increased by BA
eff↓, and antioxidant NAC treatment markedly inhibited the effect of BA on apoptosis, cell cycle arrest, and proliferation.
P53↑, BA dose-dependently increased p53 expression in KB cells and implanted tumors.
STAT3↓, Inhibition of STAT3 Signaling Is Involved in BA-Induced Suppression of Cell Proliferation
cycD1/CCND1↑, We found that BA mainly increased the mRNA expression of cyclin D1 but had no significant effect on cyclin E, CDK2, CDK4, or CDK6 expression.

2738-

BetA,

Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vivo,

NA,

mice

TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

1577-

Citrate,

Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet

in-vivo,

PC,

30 mg·kg ·day citrate(injection)

mice

in-vitro,

PC,

PANC1

10 mmol·L citrate

in-vitro,

PC,

PATU-8988

in-vitro,

PC,

MIA PaCa-2

Apoptosis↑, citrate treatment demonstrates signifcant effcacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo
TumCP↓,
TumCG↑,
SPARC↑, citrate treatment reveal decreased glycolysis and oxygen consumption in tumor cells, increased SPARC protein expression, and the promotion of M1 polarization
Glycolysis↓,
OCR↓,
pol-M1↑, repolarizing M2 macrophages into M1 macrophages
pol-M2 MC↓, shift from the M2 phenotype to the M1 phenotype in TAMs following citrate treatment
Weight∅, no signficant changes in body weight observed between the two groups
ATP↓, decreased ATP production of pancreatic tumors in vivo
ECAR↓, signifcantly reduced glycolytic flux, glycolytic reserve, glycolytic capacity, and acidifcation rates
mitResp↓, decreased basal mitochondrial respiration
i-ATP↑, decrease in intracellular ATP levels
p65↓, citrate effectively suppressed the expression of RELA findings collectively underscore the critical role of RELA in mediating citrate's regulation of glycolysis and suppression of pancreatic cancer progression
i-Ca+2↑, inhibition of RELA resulted in a rapid elevation of intracellular calcium levels
eff↓, overexpression of RELA and SPARC knockdown attenuated the therapeutic effects of citrate

1574-

Citrate,

Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway

in-vitro,

Lung,

A549

5,10,15mM

in-vitro,

Melanoma,

WM983B

in-vivo,

NA,

4 g/kg citrate twice a day for 4 week

mice. Plasma levels in chronically treated animals were approximately 3 mM

TumCG↓,
eff↑, additional benefit accrued in combination with cisplatin
T-Cell↑, significantly higher infiltrating T-cells
p‑IGF-1R↓, citrate inhibited IGF-1R phosphorylation
p‑Akt↓, inhibited AKT phosphorylation
PTEN↑, activated PTEN
p‑eIF2α↑, increased expression of p-eIF2a p-eIF2a was decreased when PTEN was depleted
OCR↓, citrate treatment of A549 cells dramatically reduced oxygen consumption
ROS↓, observed a decrease in ROS in A549
ECAR∅, acidification rate (ECAR) and found it to be unchanged
IL1↑, s (e.g. interleukin-1, tumor necrosis factor-alpha, etc) and anti-inflammatory cytokines (e.g. interleukin-10 and interleukin 1 receptor antagonist) are activated
TNF-α↑,
IL10↑,
IGF-1R↓, Citrate Inhibits IGF-1R Activation And Its Downstream Pathway
eIF2α↑, eIF2α activity was increased in A549 cells after citrate treatment
PTEN↑, PTEN was activated
TCA↓,
Glycolysis↓, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
selectivity↑, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
*toxicity∅, Chronic citrate treatment was non-toxic as evidenced by gross pathology in numerous organs (liver, lung, spleen and kidney)
Dose∅, corresponding to approximately 56 g of citrate in a 70 kg person

4761-

CoQ10,

Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer

in-vitro,

PC,

in-vivo,

PC,

MIA PaCa-2 xenograft mouse model

*ETC↝, Coenzyme Q10 is a critical cofactor in the electron transport chain with complex biological functions that extend beyond mitochondrial respiration.
ROS↑, This study demonstrates that delivery of oxidized Coenzyme Q10 (ubidecarenone) to increase mitochondrial Q-pool is associated with an increase in ROS generation, effectuating anti-cancer effects in a pancreatic cancer model.
*antiOx↑, In addition to its role in ETC function, CoQ10 has phenolic antioxidant activity via its ability to undergo hydrogen abstraction by free radicals6
ROS↑, Paradoxically, CoQ10 also exhibits pro-oxidant activity that occurs either due to a CoQ10 semiquinone reaction5 or due to a reaction with oxygen when CoQ10 is in its oxidized state
OCR↓, Delivery of supraphysiologic levels of ubidecarenone via BPM31510 decreases oxygen consumption rates (OCR) in pancreatic cancer
MMP↓, Ubidecarenone enhances succinate-dependent and glycerol-3-phosphate-dependent ROS generation, mitochondrial membrane depolarization, and regulated cell death
TumCD↑,
TumCG↓, BPM31510 (25 mg/kg, b.i.d) resulted in a significant decrease in tumour growth by day 45 after inoculation compared to saline-treated mice
other↝, NOTE: this is oxidized CoQ10, not the same as CoQ10!!!!!!

951-

DHA,

Docosahexaenoic Acid Attenuates Breast Cancer Cell Metabolism and the Warburg Phenotype by Targeting Bioenergetic Function

in-vitro,

BC,

BT474

25-100uM

in-vitro,

BC,

MDA-MB-231

in-vitro,

Nor,

MCF10

Hif1a↓, in the malignant cell lines but not in the non-transformed cell line. ****
GLUT1↓, Downstream targets of HIF-1a, including glucose transporter 1 (GLUT 1) and lactate dehydrogenase (LDH), were decreased
LDH↓,
GlucoseCon↓,
lactateProd↓,
ATP↓, 50%
p‑AMPK↑,
ECAR↓, DHA significantly decreased basal ECAR by over 60%
OCR↓, basal OCR was decreased by 80%
*toxicity↓, while not affecting non-transformed MCF-10A cells

1621-

EA,

The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art

Review,

Var,

AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

694-

EGCG,

Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways

in-vitro,

BC,

MCF-7

~0.2 mg/ml, in tissue culture

Glycolysis↓, MGT might similarly act as a glycolysis inhibitor
GAPDH↓,
ROS↑, Tea cathechins may act both as anti-oxidant and as pro-oxidants
OCR↓,
ECAR↓,
mTOR↓,
OXPHOS↓,

5526-

EP,

Nanosecond Pulsed Electric Field Modulates Electron Transport and Mitochondrial Structure and Function

Review,

Var,

CellMemb↑, In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the cytosol and mitochondria, and Electron Transport Chain (ETC) in cell cultures.
ROS↑, nsPEF and rotenone synergistically enhanced ROS production in intact cells suggesting that nsPEF and rotenone act at different Complex I sites.
ETC↝, A reduced cellular oxygen consumption after nsPEFs treatment indicates an alteration of the ETC at Complex I in intact and permeabilized cells as well as in isolated hepatocyte mitochondria
OCR↓,
MMP↓, collapse the mitochondrial membrane potential and cause cell death.

5529-

EP,

Effects of nsPEFs on Electron Transport and Mitochondrial Structures and Functions

Review,

Var,

ETC↓, NsPEFs attenuated electron transport (ET) (O2 consumption) in the electron transport chain (ETC) of intact and permeabilized cells
OCR↓,
CellMemb↑,
mt-ROS↑, Effects of nsPEFs on increases in mROS were synergistic with the complex I inhibitor rotenone
MMP↓, dissipating the ΔΨm

5148-

GamB,

Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics

Review,

Var,

AntiCan↑, In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent.
angioG↓, anti-angiogenesis, and chemo-/radiation sensitizer activities
ChemoSen↑, Moreover, GA has shown chemotherapy/radiation sensitization properties in different types of cancers
RadioS↑,
VEGF↓, Figure 2
MMP2↓,
MMP9↓,
Telomerase↓,
TrxR↓,
ERK↓,
HSP90↓,
ROS↑,
SIRT1↑,
survivin↓,
cFLIP↓,
Casp3↑,
Casp8↑,
Casp9↑,
BAD↓,
BID↓,
Bcl-2↓,
BAX↑,
STAT3↓,
hTERT/TERT↓,
NF-kB↓,
Myc↓,
Hif1a↓,
FOXD3↑,
BioAv↓, Unfortunately, the aqueous solubility of GA (0.013 mg/mL) is very low, thus limiting its clinical application.
BioAv↑, For example, GA can be coupled with alkanolamines to improve aqueous solubility and achieve equivalent anti-proliferation effects
P53↑, This inhibition was co-related with increase of p53 levels and reduced bcl-2 levels
eff↓, Such effect was received for GA due to production of ROS which can be removed by N-acetyl-L-cysteine (NAC, a ROS inhibitor)
OCR↓, GA exhibited a dose-dependent generation of intracellular ROS levels and lowered the oxygen consumption rate and the mitochondrial membrane potential.
MMP↓,
PI3K↓, GA happens to promote antimetastasis properties in melanoma cells by active inhibition of PI3K/Akt and ERK signaling pathways
Akt↓,
BBB↑, This study demonstrated successful uptake of GA through blood-brain barrier (BBB)
TumCG↓, GA-based nanomedicine is efficient in targeting tumors, capable to inhibit tumor growth, metastasis, angiogenesis, and reverse drug resistance
TumMeta↓,
BioAv↑, deliver GA using nanoparticles for enhanced solubility, bioavailability, adsorption and tumor imaging and targeting

1625-

HCA,

In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase

Review,

Nor,

aged yeast cells

CRM↑, Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy.
ACLY↓, competitive inhibitor of ATP citrate lyase (ACLY)
TumAuto↑, promoting autophagy.
Inflam↓, reduce inflammation and tumour development
TumCG↓,
toxicity∅, HCA appear to have a low or negligible impact in terms of acute or chronic toxicity, genotoxicity, reproductive failure and teratogenicity
lipoGen↓, decreases lipogenesis, insulin resistance, inflammation and oxidative stress
*ROS↓, H2O2 treatment: Strikingly, the molecule was able to largely prevent the massive cell death (PI+ cells) caused by the intense oxidative stress. In parallel there was a sharp increase of live cells with high ROS levels
*OCR↓, chronic exposure to 5 mM HCA (from cell seeding) down-regulated yeast OCR

2879-

HNK,

Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function

in-vitro,

Lung,

H226

in-vivo,

NA,

mouse

tumCV↓, honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5%
selectivity↑,
TumCP↓, In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis.
TumCCA↑,
Apoptosis↑,
mt-ROS↑, interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, : mitochondrial ROS generation
Casp3↑, cells treated with honokiol showed a significant increase in caspase 3/7 activity, which occurred in dose- and time-dependent manners
Casp7↑,
OCR↓, Honokiol caused a fast and concentration-dependent decrease in basal oxygen consumption rate (OCR) in both cell lines
Cyt‑c↑, cytochrome c release was increased in honokil treated mouse lung SCC tissue
ATP↓, found a dramatic decrease in cellular ATP content
mitResp↓, Honokiol inhibits mitochondrial respiration and decreases ATP levels in H226 and H520 cells, which may elevate AMP and the intracellular AMP/ATP ratio, leading to activation of the AMPK
AMP↑,
AMPK↑,

2883-

HNK,

Honokiol targets mitochondria to halt cancer progression and metastasis

Review,

Var,

ChemoSen↑, Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death
BBB↓, HNK is also capable of crossing the BBB
Ca+2↑, HNK promotes human glioblastoma cancer cell apoptosis via regulation of Ca(2+) channels
Cyt‑c↑, release of mitochondrial cytochrome c and activation of caspase-3
Casp3↑,
chemoPv↑, potent chemopreventive agent against lung SCC development in a carcinogen-induced lung SCC murine model
OCR↓, HNK treatment results in a decreased oxygen consumption rate (OCR) in whole intact cells, rapidly, and persistently inhibiting mitochondrial respiration, which leads to the induction of apoptosis
mitResp↓,
Apoptosis↑,
RadioS↑, Honokiol as a chemo- and radiosensitizer
NF-kB↓, HNK as an anticancer drug is its potential to inhibit multiple important survival pathways, such as NF-B and Akt
Akt↓,
TNF-α↓, by inhibiting TNF-induced nerve growth factor IB expression in breast cancer cells
PGE2↓, reduced prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) secretion levels
VEGF↓,
NO↝, HNK inhibits cancer cell migration by targeting nitric oxide and cyclooxygenase-2 or Ras GTPase-activating-like protein (IQGAP1) [
COX2↓,
RAS↓,
EMT↓, HNK can reverse the epithelial-mesenchymal-transition (EMT) process, which is a key step during embryogenesis, cancer invasion, and metastasis,
Snail↓, HNK reduced the expression levels of Snail, N-cadherin and -catenin, which are mesenchymal markers, but increased E-cadherin,
N-cadherin↓,
β-catenin/ZEB1↓,
E-cadherin↑,
ER Stress↑, induction of ER stress
p‑STAT3↓, HNK inhibited STAT3 phosphorylation
EGFR↓, inhibiting EGFR phosphorylation and its downstream signaling pathways such as the mTOR signaling pathway
mTOR↓,
mt-ROS↑, We demonstrated that HNK treatment suppresses mitochondrial respiration and increases generation of ROS in the mitochondria, leading to the induction of apoptosis in lung cancer cells
PI3K↓, inhibition of PI3K/Akt/ mTOR, EMT, and Wnt signaling pathways.
Wnt↓,

2178-

itraC,

Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer

in-vivo,

CRC,

HCT116

xenograft model in tumor-bearing mice

TumCG↓, We found that itraconazole could inhibit tumor growth and glycolysis
Glycolysis↓, itraconazole could repress CRC tumor growth by inhibiting glycolysis
CEBPB?, CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression
ENO1↓, glycolysis enzymes (ENO1, LDHA, PGK1, PKM and GAPDH) was significantly decreased after itraconazole treatment
LDHA↓,
PKM2↓,
GAPDH↓,
ECAR↓, itraconazole treatment could significantly reduce ECAR and OCR
OCR↓,

4779-

Lyco,

Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells

in-vitro,

PC,

PANC1

ROS↓, The results show that the lycopene decreased intracellular and mitochondrial ROS levels, mitochondrial function (determined by the mitochondrial membrane potential and oxygen consumption rate),
NF-kB↓, NF-κB activity, and expression of NF-κB-dependent survival genes in PANC-1 cells.
tumCV↓, Lycopene reduced cell viability with increases in active caspase-3 and the Bax to Bcl-2 ratio in PANC-1 cells
Casp3↑,
Apoptosis↑, Lycopene Induces Apoptosis in PANC-1 Cells
OCR↓, Lycopene Decreases Intracellular and Mitochondrial ROS Levels and OCR in PANC-1 Cells
MMP↓, Lycopene Decreases MMP in PANC-1 Cells
CIP2A↓, Lycopene Decreases Expression of cIAP1, cIAP2, and Survivin in PANC-1 Cells
survivin↓,
Casp3↑, Thus, lycopene induces caspase-3-dependent apoptosis and increased the Bax to Bcl-2 ratio in PANC-1 cells.
Bax:Bcl2↑,

4789-

Lyco,

Inhibitory Effect of Lycopene on Amyloid-β-Induced Apoptosis in Neuronal Cells

in-vitro,

AD,

SH-SY5Y

 amyloid-β-induced alterations. Amyloid-β induces its neurotoxicity in a variety of ways, including accelerating mitochondrial dysfunction, ROS production, and neuronal death

*antiOx↑, Lycopene is an antioxidant protecting from oxidative stress-induced cell damage
*ROS↓, Lycopene inhibited apoptosis by reducing ROS, and by inhibiting mitochondrial dysfunction and NF-κB-target gene Nucling expression in neuronal cells.
*NF-kB↓,
*neuroP↑, Lycopene may be beneficial for preventing oxidative stress-mediated neuronal death in patients with neurodegeneration.
*MMP↓, As shown in Figure 3C, amyloid-β increased the ratio of green to red fluorescence in the cells, which reflects a decrease in MMP in amyloid β-stimulated cells
*mtDam↓, Lycopene suppressed decrease in OCR in amyloid-β-stimulated cell, suggesting that lycopene prevents mitochondrial damage induced by amyloid-β in the cells.
*OCR↓, In the present study, lycopene significantly inhibited amyloid-β-induced mitochondrial dysfunction, which was proven by its protective effect in reducing both MMP and OCR.

184-

MFrot,

MF,

Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells

in-vitro,

GBM,

GBM

 80mT pulsed

ROS↑, sOMF
mitResp↓, Inhibit Mitochondrial Respiration
mtDam↑, Produce Loss of Mitochondrial Integrity
Dose↝, Repeated intermittent sOMF was applied for 2 hours at a specific frequency, in the 200-300 Hz frequency range, with on-off epochs of 250 or 500 ms duration.
MMP?, ROS generation has been shown to be driven, in part, by elevated mitochondrial membrane chemiosmotic potential (ΔΨ) and ubiquinol (QH2)
OCR↓, Immediately after cessation of field rotation we observe a loss of mitochondrial integrity (labeled LMI), with a very rapid increase in O2 consumption
mt-H2O2↑, We have previously demonstrated that sOMF treatment of cells generates superoxide/hydrogen peroxide in the mitochondrial matrix
eff↓, we repeated the same experiment in the presence of Trolox, which protects thiols from ROS oxidation (47). sOMF treatment of RLM in State 3u pre-treated with Trolox (15 μM), show minimal inhibition,
SDH↓, SDH Inhibition by sOMF in State 3u RLM Is Caused by ROS Generation
Thiols↓, suggest that thiol oxidation in SDH may result from sOMF.
GSH↓, Glutathione in the mitochondrial matrix can provide some protection from ROS, but after solubilizing the mitochondria, this protection is lost and the SDH becomes more sensitive to sOMF.
TumCD↑, sOMF is highly effective at killing non-dividing GBM cell cultures,
Casp3↑, caspase-3 activation 1 h after sOMF
Casp7↑, rapid activation of caspase-3/7
MPT↑, OMF-treated cell that causes near simultaneous MPT, release of cytochrome c and other apoptosis-inducing factors, resulting in caspase-3/7 activation in these GBM cells.
Cyt‑c↑,
selectivity↑, differential sensitivity to sOMF of cancer cells over ‘normal’ cells becomes apparent. rapid increase in the reactive oxygen species (ROS) in the mitochondria to cytotoxic levels only in cancer cells, and not in normal human cortical neurons
GSH/GSSG↓, increasing GSSG/GSH ratio
ETC↓, completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM)

2041-

PB,

The Effect of Glucose Concentration and Sodium Phenylbutyrate Treatment on Mitochondrial Bioenergetics and ER Stress in 3T3-L1 Adipocytes

in-vitro,

Nor,

3T3

*mitResp↓, Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration.
*ER Stress↓, sodium phenylbutyrate (PBA), an agent that reduces ER stress in adipocytes
MMP↓, Sodium phenylbutyrate (PBA) reduces protein succination and mitochondrial membrane potential in adipocytes matured in high glucose
GlucoseCon↓, PBA inhibits adipocyte maturation and glucose uptake
OCR↓, We observed that PBA reduced adipocyte glucose uptake (Figure 5 D), suggesting that overall the OCR is lower due to decreased metabolic flux coupled with selective reductions in mitochondrial protein content
CHOP↑, Both normal and high glucose adipocytes proceed through adipogenesis by activation of the UPR but only in high glucose is this accompanied by increased protein succination and CHOP production.

1672-

PBG,

The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers

Review,

BC,

ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

4922-

PEITC,

Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms

Review,

Var,

Risk↓, strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer.
AntiCan↑, Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects.
TumCP↓, PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis
TumMeta↓,
ChemoSen↑, combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy
*BioAv↑, ITCs are released from glucosinolates by the action of the enzyme myrosinase. The enzyme myrosinase can be activated by cutting or chewing the vegetables, but heating can destroy its activity
*other↝, Although water cress and broccoli are known to be the richest source, PEITC can also be obtained from turnips and radish
*Dose↝, In a study conducted with human volunteers, approximately 2 to 6 mg of PEITC was found to be released by the consumption of one ounce of watercress
Dose↓, significant anti-cancer effects can be achieved at micromolar concentrations of PEITC.
*BioAv↑, PEITC is highly bioavailable after oral administration. A single dose of 10–100 μmol/kg PEITC in rats resulted in bioavailability ranging between 90–114%
*Dose↝, Furthermore, about 928.5±250nM peak plasma concentration of PEITC was achieved in human subjects, after the consumption of 100g watercress.
*Half-Life↝, time to reach peak plasma concentration was observed to be 2.6h±1.1h with a t1/2 4.9±1.1h
*toxicity↝, long term studies are required to establish the safety profile of PEITC, since regular intake of PEITC can cause its accumulation resulting in cumulative effects, which could be toxic.
GSH↓, The conjugation of PEITC with intracellular glutathione and the subsequent removal of the conjugate result in depletion of glutathione and alteration in redox homeostasis leading to oxidative stress
ROS↑, PEITC-mediated generation of reactive oxygen species (ROS) is known to be a general mechanism of action leading to cytotoxic effects, especially specific to cancer cells
CYP1A1↑, PEITC on one hand causes induction of CYP1A1 and CYP1A2; however, it inhibits activity of certain CytP450 enzymes, such as CYP2E1, CYP3A4 and CYP2A3
CYP1A2↑,
P450↓,
CYP2E1↑,
CYP3A4↓,
CYP2A3/CYP2A6↓,
*ROS↓, PEITC treatment caused a significant increase in the activities of ROS detoxifying enzymes such as glutathione peroxidase1, superoxide dismutase 1 and 2. This was also confirmed in human study where subjects were administered watercress, a major sour
*GPx1↑,
*SOD1↑,
*SOD2↑,
Akt↓, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types
EGFR↓, PEITC is also known to inhibit EGFR and HER2, which are important growth factors and regulators of Akt in different cancer models
HER2/EBBR2↓,
P53↑, PEITC-mediated activation of another tumor suppressor, p53 was observed in oral squamous cell carcinoma, causing G0/G1 phase arrest in multiple myeloma,
Telomerase↓, PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells
selectivity↑, generation of reactive oxygen species (ROS), which also has been shown to be the basis of selectivity of PEITC toward cancer cells leaving normal cells undamaged [
MMP↓, ROS generation by PEITC leads to mitochondrial deregulation and modulation of proteins like Bcl2, BID, BIM and BAX, causing the release of cytochrome c into cytosol leading to apoptosis
Cyt‑c↑,
Apoptosis↑,
DR4↑, induction of death receptors and Fas-mediated apoptosis
Fas↑,
XIAP↓, PEITC-mediated suppression of anti-apoptotic proteins like XIAP and survivin, which are up-regulated in cancer cells
survivin↓,
TumAuto↑, PEITC induces autophagic cell death in cancer cells
Hif1a↓, PEITC directly or indirectly suppresses HIF1α
angioG↓, is possible that PEITC can block angiogenesis by non-hypoxic mechanisms also.
MMPs↓, Various studies with PEITC have shown suppression of invasion through inhibition of matrix metalloproteinases along with anti-metastatic effects caused by suppression of ERK kinase activity and transcriptional activity of NFkB
ERK↓,
NF-kB↓,
EMT↓, PEITC was also known to inhibit processes, such as epithelial to mesenchymal transition (EMT), cell invasion and migration, which are essential pre-requisites for metastasis
TumCI↓,
TumCMig↓,
Glycolysis↓, reduced rates of glycolysis in PEITC-treated cells and depletion of ATP lead to death in prostate cancer cells
ATP↓,
selectivity↑, PEITC (5μM) treatment suppressed glycolysis in the cancer cells, but no changes were observed in normal cells.
*antiOx↑, the antioxidant effect is achieved at very low ITC levels in normal cells as shown in various animal models
Dose↝, At higher concentrations, ITCs may generate ROS by depleting antioxidant levels. PEITC is known to cause ROS generation, which is the major mechanism of toxicity in cancer cells
other↝, There is a continuous leakage of electrons from the electron transport chain (ETC), which is major source of ROS production. PEITC causes generation of endogenous ROS by disrupting mitochondrial respiratory chain
OCR↓, PEITC also inhibits mitochondrial complex III activity and reduces the oxygen consumption rate in prostate cancer cells
GSH↓, PEITC binds to GSH and causes its depletion in cancer cells leading to ROS-induced cell damage
ITGB1↓, PEITC was found to inhibit major integrins, such as ITGB1, ITGA2 and ITGA6 in prostate cancer cells
ITGB6↓,
ChemoSen↑, Using pre-clinical studies, improved outcomes were observed when the conventional agents, such as docetaxel, metformin, vinblastine, doxorubicin and HDAC inhibitors were combined with PEITC

910-

QC,

The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism

tumCV↓,
Apoptosis↑,
PI3k/Akt/mTOR↓, QUE induces cell death by inhibiting PI3K/Akt/mTOR and STAT3 pathways in PEL cells
Wnt/(β-catenin)↓, reducing β-catenin
MAPK↝,
ERK↝, ERK1/2
TumCCA↑, cell cycle arrest at the G1 phase
H2O2↑,
ROS↑,
TumAuto↑,
MMPs↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
P53↑,
Casp3↑,
Hif1a↓, by inactivating the Akt-mTOR pathway [64,74] and HIF-1α
cFLIP↓,
IL6↓, QUE decreased the release of interleukin-6 (IL-6) and IL-10
IL10↓,
lactateProd↓,
Glycolysis↓, It is suggested that QUE alters glucose metabolism by inhibiting monocarboxylate transporter (MCT) activity
PKM2↓,
GLUT1↓,
COX2↓,
VEGF↓,
OCR↓,
ECAR↓,
STAT3↓,
MMP2↓, Consistently, QUE was able to reduce the protein levels of MMP-2, MMP-9, VEGF and mTOR, and p-Akt in breast cancer cell lines
MMP9:TIMP1↓,
mTOR↓,

2190-

SK,

Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway

in-vitro,

HCC,

HCCLM3

TumCP↓, shikonin inhibited the proliferation, migration, and invasiveness of HCCLM3 cells, and promoted cell apoptosis in a dose-dependent manner
TumCMig↓,
TumCI↓,
Apoptosis↑,
MMP↓, shikonin affected mitochondrial function by disrupting mitochondrial membrane potential and oxidative stress (OS) status.
ROS↑,
OCR↓, shikonin decreased the oxygen consumption rate of HCCLM3 cells, as well as the levels of ATP and metabolites involved in the tricarboxylic acid cycle (TCA cycle)
ATP↓,
PKM2↓, Shikonin decreased the expression of PKM2 in the mitochondria

2414-

β‐Ele,

Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF-7

in-vivo,

NA,

mice

TumCMig↓, β‐elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo
TumCI↓,
TumMeta↓, β‐Elemene inhibited breast cancer metastasis in lung and liver in mice
Glycolysis↓, β‐Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose
GlucoseCon↓,
lactateProd↓, and the production of pyruvate and lactate
PKM2↓, through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2.
EGFR↓, blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5
GLUT1↓,
LDHA↓,
ECAR↓, In our research, β‐elemene decreased both ECAR and OCR in MCF‐7 cells, but the cancer cells still survived.
OCR↓,

Showing Research Papers: 1 to 30 of 30

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 30

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, GPx1↑, 1, lipidDe↓, 1, ROS↓, 3, SOD1↑, 1, SOD2↑, 1,

Mitochondria & Bioenergetics ⓘ

ETC↝, 1, mitResp↓, 1, MMP↓, 1, mtDam↓, 1, OCR↓, 4,

Core Metabolism/Glycolysis ⓘ

ACC↓, 1, p‑ACC↑, 1, AMPK↑, 1, p‑AMPK↑, 1, ECAR↑, 1, FAO↑, 1, Glycolysis↑, 2, HK2↑, 1, LDHA↑, 1, PDKs↓, 1, PKM2↑, 1, SREBP1↓, 1,

Transcription & Epigenetics ⓘ

other↝, 1,

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,

Drug Metabolism & Resistance ⓘ

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

Functional Outcomes ⓘ

neuroP↑, 1, toxicity↓, 1, toxicity↝, 1, toxicity∅, 1,
Total Targets: 34

Scientific Paper Hit Count for: OCR, Oxygen consumption rate

3 Betulinic acid
2 Citric Acid
2 Electrical Pulses
2 Honokiol
2 Lycopene
1 3-bromopyruvate
1 Auranofin
1 Alpha-Lipoic-Acid
1 Baicalin
1 Berberine
1 Coenzyme Q10
1 Docosahexaenoic Acid
1 Ellagic acid
1 EGCG (Epigallocatechin Gallate)
1 Gambogic Acid
1 HydroxyCitric Acid
1 itraconazole
1 Magnetic Field Rotating
1 Magnetic Fields
1 Phenylbutyrate
1 Propolis -bee glue
1 Phenethyl isothiocyanate
1 Quercetin
1 Shikonin
1 β‐Elemene

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#:846  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

OCR Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

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 ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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