mitResp Cancer Research Results

mitResp, mitochondrial respiration: Click to Expand ⟱

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Mitochondrial respiration plays a crucial role in the development and progression of cancer. Cancer cells often exhibit altered metabolic profiles, including changes in mitochondrial respiration, to support their rapid growth and proliferation.

In cancer cells, mitochondrial respiration is often downregulated, and instead, they rely on glycolysis for energy production, even in the presence of oxygen. This phenomenon is known as the "Warburg effect."

There are several key players involved in the regulation of mitochondrial respiration in cancer cells, including:

Pyruvate dehydrogenase (PDH): a critical enzyme that converts pyruvate into acetyl-CoA, which is then fed into the citric acid cycle.
Citrate synthase: an enzyme that catalyzes the first step of the citric acid cycle.
Succinate dehydrogenase (SDH): an enzyme that participates in both the citric acid cycle and the electron transport chain.
Cytochrome c oxidase (COX): the final enzyme in the electron transport chain, responsible for generating ATP.
Alterations in the expression and activity of these enzymes can impact mitochondrial respiration in cancer cells. For example, increased expression of PDH and citrate synthase can enhance mitochondrial respiration, while decreased expression of SDH and COX can impair it.

Additionally, various transcription factors and signaling pathways regulate mitochondrial respiration in cancer cells, including:

HIF-1α (hypoxia-inducible factor 1 alpha): a transcription factor that promotes glycolysis and suppresses mitochondrial respiration in response to hypoxia.
c-Myc: a transcription factor that regulates the expression of genes involved in mitochondrial respiration and biogenesis.
PI3K/Akt/mTOR: a signaling pathway that promotes cell growth and proliferation, in part by regulating mitochondrial respiration.

Scientific Papers found: Click to Expand⟱

5257-

3BP,

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Review,

Var,

Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

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↓,

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

1368-

Ash,

Cisplatin,

Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’

in-vitro,

Colon,

HT-29

1 μg/mL, 5 μg/mL and 10 μg/mL W. somnifera for 48 h

in-vitro,

BC,

MDA-MB-231

tumCV↓,
*toxicity↓, However, in non-cancer cells (MCF10A) there was no reduction in cell viability compared to non-treatment
ROS↑, only in cancer cells ****
mitResp↓,
ChemoSen↑, ‘Priming’ with W. somnifera (treatment: 48 h prior to 100 μM cisplatin)

1355-

Ash,

Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species

in-vitro,

BC,

MDA-MB-231

2.5 or 5 µM WA

WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis.

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.

5850-

CAP,

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

Review,

Var,

TRPV1↑, Capsaicin functions as a classic agonist of the TRPV1 receptor
Ca+2↑, multiple mechanisms such as increase of intracellular calcium, induction of calpain activity, reactive oxygen species (ROS) generation, inhibition of coenzyme Q, suppression of mitochondrial respiration,
ROS↑,
mitResp↓,
ChemoSen↑, capsaicin promotes the apoptotic activity of cancer chemotherapy agents by multiple mechanisms
P-gp↓, capsaicin has been reported to inhibit p-glycoprotein efflux transporters in KB-C2 human endocervical adenocarcinoma cells.

1259-

CAP,

Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells

in-vitro,

Lung,

H1299

in-vitro,

Lung,

A549

in-vitro,

Lung,

H23

in-vitro,

Lung,

H2009

Hif1a↓, Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein
PDK1↓,
GLUT1↓,
ROS↑,
mitResp↓,
ATP↓,

6002-

CGA,

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

Review,

Var,

Review,

Diabetic,

Review,

AD,

Review,

Park,

Review,

Stroke,

*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms

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

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↓,

1175-

IVM,

PDT,

Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors

in-vitro,

Var,

Hypoxia↓,
mitResp↓,
ROS↑, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.

2491-

MET,

Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

in-vivo,

Nor,

Rats

*glucoNG↓, Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
*glucose↓, Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production (EGP)
*mitResp↓, These findings are supported by our data showing that metformin significantly inhibited mitochondrial respiration from G-3-P

2249-

MF,

Pulsed electromagnetic fields modulate energy metabolism during wound healing process: an in vitro model study

in-vitro,

Nor,

L929

4mT, 80 Hz

 pulsed burst (burst width, 2 ms; pulse width, 10.5 ms).

*TumCMig↑, PEMFs with specific parameter (4mT, 80 Hz) promoted cell migration and viability.
*tumCV↑,
*Glycolysis↑, PEMFs-exposed L929 cells was highly glycolytic for energy generation
*ROS↓, PEMFs enhanced intracellular acidification and maintained low level of intracellular ROS in L929 cells.
*mitResp↓, shifting from mitochondrial respiration to glycolysis
*other↝, Furthermore, the analysis of ECAR/ OCR basal ratio demonstrated a tendency toward to glycolytic phenotype in L929 cells under PEMF exposure, compared to control group
*OXPHOS↓, PEMFs promoted the transformation of energy metabolism pattern from oxidative phosphorylation to aerobic glycolysis
*pH↑, result of pH detection by flow cytometer indicated the pH level in L929 cells was significantly increased in the PEMFs group compared to the control group
*antiOx↑, PEMFs upregulated the expression of antioxidant or glycolysis related genes
*PFKM↑, Pfkm, Pfkl, Pfkp, Pkm2, Hk2, Glut1, were also significantly up-regulated in the PEMFs group
*PFKL↑,
*PKM2↑,
*HK2↑,
*GLUT1↑,
*GPx1↑, GPX1, GPX4 and Sod 1 expression were significantly higher in the PEMFs group compared to the control group
*GPx4↑,
*SOD1↑,

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)

1271-

NCL,

Niclosamide inhibits ovarian carcinoma growth by interrupting cellular bioenergetics

vitro+vivo,

Ovarian,

SKOV3

Wnt/(β-catenin)↓,
mTOR↓,
STAT3↓,
NF-kB↓,
NOTCH↓,
TumCG↓,
Apoptosis↑,
MEK↓, inactivating MEK1/2-ERK1/2
ERK↓,
mitResp↓,
Glycolysis↓, aerobic glycolysis
ROS↑, abolishment of the excess ROS production with NAC (10 mM) abrogated the Niclosamide-induced cell apoptosis under glucose deprivation
JNK↑,

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.

4956-

PEITC,

Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells

vitro+vivo,

Lung,

A549

 IC50 value from 11.6 μM for PEITC down to 4.1 μM for LBL21

GSH↓, synthetic analog of PEITC with superior in vitro and in vivo antitumor effects. Mechanistic study showed that LBL21 induced a rapid depletion of intracellular glutathione (GSH), leading to abnormal ROS accumulation
ROS↑,
mtDam↑, and mitochondrial dysfunction, evident by a decrease in mitochondrial respiration and transmembrane potential.
mitResp↓,
MMP↓,
CSCs↓, Importantly, LBL21 exhibited the ability to abrogate stem cell-like cancer side population (SP) cells in non-small cell lung cancer A549
OCT4↓, with a downregulation of stem cell markers including OCT4, ABCG2, SOX2 and CD133.
ABC↓,
SOX2↓,
CD133↓,
CD44↓, LBL21 caused a significant decrease in various CSC biomarkers CD44, CD133, OCT4, ABCG2, SOX2, ALDH2 and NANOG in mRNA expression levels
ALDH↓,
Nanog↓,
TumCG↓, LBL21 substantially suppressed tumor growth in A549 xenograft mice

2942-

PL,

Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems

in-vitro,

CRC,

CT26

in-vitro,

CRC,

DLD1

in-vivo,

CRC,

CT26

CT26 tumor-bearing mice

ROS↑, known to selectively kill tumor cells via perturbation of reactive oxygen species (ROS) homeostasis
GSH↓, PL induced excessive production of ROS due to depletion of glutathione and inhibition of thioredoxin reductase
TrxR↓,
RadioS↑, PL enhanced both the intrinsic and hypoxic radiosensitivity of tumor cells
DNAdam↑, inked to ROS-mediated increase of DNA damage, G2/M cell cycle arrest, and inhibition of cellular respiration
TumCCA↑,
mitResp↓,
GSTs↓, PL proved to perturb GSH system by inhibition of glutathione S-transferase (GST) that catalyzes the conjugation of GSH with its substrate
OS↑, delays tumor growth and improves the survival rate of tumor-bearing mice.

1201-

QC,

Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1

in-vivo,

BC,

 female breast cancer mice (BALB/c) model.

mitResp↓, significant reduction in the intracellular mitochondrial respiration
Glycolysis↓,
ATP↓,
ROS↑,
GSH↓,
TumMeta↓,
Apoptosis↑,
FAO↓,

5022-

UA,

Ursolic Acid’s Alluring Journey: One Triterpenoid vs. Cancer Hallmarks

Review,

Var,

TumCP↓, inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment
Apoptosis↑,
angioG↑,
TumMeta↓,
BioAv↓, acknowledges hurdles related to UA’s low bioavailability,
Hif1a↓, graphical abstract
Glycolysis↓,
mitResp↓,
Akt↓,
MAPK↓,
ERK↓,
mTOR↓,
P53↑,
P21↑,
E2Fs↑,
STAT3↓,
MMP↓,
NLRP3↓,
iNOS↓,
CHK1↓,
Chk2↓,
BRCA1↓,
E-cadherin↑,
N-cadherin↓,
Casp↑,
p62↓,
LC3II↑,
Vim↓,
ROS↑, administration of UA has effectively modulated the generation of both cellular and mitochondrial ROS
CSCs↓, This, in turn, triggers a response in embryonic CSCs known as DNA damage response (DDR), strongly suggesting the potential for UA-induced cell death
DNAdam↑,
GutMicro↑, UA has shown potential in modulating the composition of the gut microbiota and improving the microenvironment within the digestive system
VEGF↓, UA treatment significantly reduced the expression of VEGF-A and FGF-β in both CRC tumors and HT-29 cells (

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 1, GPx↑, 1, GPx1↑, 1, GPx4↑, 1, GSH↑, 1, HO-1↑, 1, MDA↓, 1, NRF2↑, 2, OXPHOS↓, 1, Prx↑, 1, ROS↓, 2, ROS∅, 1, SOD↑, 1, SOD1↑, 1, SOD2↑, 1,

Mitochondria & Bioenergetics ⓘ

mitResp↓, 3,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, glucoNG↓, 1, glucose↓, 2, Glycolysis↑, 1, HK2↑, 1, LDH↓, 1, PFKL↑, 1, PFKM↑, 1, PKM2↑, 1, PPARα↝, 1,

Cell Death ⓘ

Casp↓, 1, Casp3?, 1, JNK↓, 1,

Transcription & Epigenetics ⓘ

other↝, 1, tumCV↑, 1,

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,

Migration ⓘ

Ca+2↓, 1, TRPC1↓, 1, TumCMig↑, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,

Barriers & Transport ⓘ

GLUT1↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL6↓, 1, Inflam↓, 1, NF-kB↓, 2, TLR4↓, 1, TNF-α↓, 1,

Cellular Microenvironment ⓘ

pH↑, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

eff↑, 1,

Clinical Biomarkers ⓘ

BP↓, 1, IL6↓, 1, LDH↓, 1,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, cardioP↑, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 2, toxicity↓, 2,
Total Targets: 57

Scientific Paper Hit Count for: mitResp, mitochondrial respiration

3 Ashwagandha(Withaferin A)
2 Capsaicin
2 Honokiol
2 Magnetic Fields
1 3-bromopyruvate
1 Alpha-Lipoic-Acid
1 Cisplatin
1 Chlorogenic acid
1 Citric Acid
1 Ivermectin
1 Photodynamic Therapy
1 Metformin
1 Magnetic Field Rotating
1 Niclosamide (Niclocide)
1 Phenylbutyrate
1 Phenethyl isothiocyanate
1 Piperlongumine
1 Quercetin
1 Ursolic acid

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

mitResp Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

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 ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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