ATP Cancer Research Results

ATP, Adenosine triphosphate: Click to Expand ⟱

Source:

Type:

Adenosine triphosphate (ATP) is the source of energy for use and storage at the cellular level.
Cellular ATP levels are critical for cell survival, and several reports have shown that reductions in cellular ATP levels can lead to apoptosis and other types of cell death in cancer cells, depending on the level of depletion.
Adenosine triphosphate (ATP) is one of the main biochemical components of the tumor microenvironment (TME), where it can promote tumor progression or tumor suppression depending on its concentration and on the specific ecto-nucleotidases and receptors expressed by immune and cancer cells.

Cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation.

Scientific Papers found: Click to Expand⟱

2424-

2DG,

SRF,

The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells

in-vitro,

HCC,

Hep3B

in-vitro,

HCC,

HUH7

ChemoSen↓, combination of 2-DG and sorafenib reduced persister tumor growth in mice
Glycolysis↓, The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG), an inhibitor of all forms of HK
HK1↓,
HK2↓,
ATP↓, reducing ATP production

5271-

3BP,

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

Review,

Var,

selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

5281-

3BP,

A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside

Case Report,

Var,

Glycolysis↓, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosphorylation.
mt-OXPHOS↓,
ATP↓, This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an “Energy Blocker”, is very rapid in killing such cells.
selectivity↑, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells.
toxicity↝, The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.
OS↑, The patient (Fig. 5) was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP.
QoL↑,

5279-

3BP,

Rad,

Abstract 5243: 3-Bromopyruvate in combination with radiation inhibits pancreatic cancer growth by dismantling mitochondria and ATP generation in a preclinical mouse model

in-vivo,

PC,

ATP↓, ATP production was severely inhibited in cancer cells treated with same concentration of 3-BP
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme of glycolysis pathway and ATP generation in cancer cells.
RadioS↑, We also observed that 3-BP in combination with low doses of irradiation was more effective in killing cancer cells than 3-BP alone.

5278-

3BP,

The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

Caco-2

in-vitro,

CRC,

SW48

ATP↓, 3-Bromopyruvate (3BP) is a pyruvate analogue with alkylating properties that depletes cellular ATP levels and induces rapid cell death in neoplastic cells with limited cytotoxic effects against normal cells.
TumCD↑,
selectivity↑,
toxicity↓, 3BP treatment led to eradication of tumours of hepatocellular carcinoma cell origin in rats without apparent cytotoxic effects [19]
OS↑, first human case report suggested that 3BP was able to prolong survival in a cancer patient diagnosed with hepatocellular carcinoma in 2012 [19,20].
HK2?, 3BP is able to dissociate and inhibit mitochondrial HKII function, thereby reducing ATP production. 3BP binding also frees up binding sites previously occupied by HKII
Cyt‑c↑, llowing pro-apoptotic molecules (such as BAX and BAD) to promote the release of cytochrome c into the cytosol and induce eventual cell death
eff↑, Raji lymphoma cells grown under hypoxic conditions were more sensitive to 3BP than in normoxia
p‑Akt↑, 3BP induces rapid AKT phosphorylation at residue Thr-308

5277-

3BP,

3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model

in-vivo,

PC,

Panc02

mouse model

HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5272-

3BP,

The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells

in-vitro,

GBM,

U87MG

in-vitro,

Nor,

HEK293

Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5263-

3BP,

CET,

3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis

in-vitro,

CRC,

DLD1

NA,

HCT116

eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

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].

5259-

3BP,

Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP

in-vivo,

HCC,

highly glycolytic cancers.  young rats. Advanced cancers (2-3cm) developed

ATP↓, Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death.
TumCD↑,
toxicity↓, In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence.
eff↑, These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
tumCV↓, The chemical agent 3-BrPA depletes ATP stores and inhibits HCC cell viability
Dose↝, administered eight treatments on successive days with 1 ml of 2 mM 3-BrPA, also in 1· PBS, pH 7.5. Injection of 3-BrPA was into the tumor.

5260-

3BP,

Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer

in-vivo,

PC,

TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA

5266-

3BP,

3-bromopyruvate-based agent KAT-101

Review,

Var,

eff↑, Upon oral administration of 3-BP-based agent KAT-101, the 3-BP derivative, being structurally similar to lactic acid, specifically binds to and enters cancer cells through monocarboxylic acid transporters (MCTs)
Glycolysis↓, KAT-101 interferes with both glycolysis and mitochondrial oxidative phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and thus limits energy supply needed by cancer cells to proliferate.
OXPHOS↓,
ATP↓,
TumCP↓,
Apoptosis↑, This induces cancer cell apoptosis and prevents cancer cell proliferation.
HK2↓, In addition, KAT-101 is able to release mitochondrial-bound hexokinase (HK) II (HK2)
MPT↑, increases the formation of mitochondrial permeability transition pores (MPTPs), which induces apoptosis.
LDH↓, KAT-101 also inhibits a variety of enzymes, including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase (PDHK).
PDH↓,

5468-

AF,

The gold complex auranofin: new perspectives for cancer therapy

Review,

Var,

TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

4383-

AgNPs,

Exploring the Potentials of Silver Nanoparticles in Overcoming Cisplatin Resistance in Lung Adenocarcinoma: Insights from Proteomic and Xenograft Mice Studies

in-vitro,

Lung,

A549

AgNPs was 23.45 nm, with zeta potentials lying on −20.33 mV.

in-vivo,

Lung,

A549

A549 and A549/DDP-bearing mice

Apoptosis↑, Silver nanoparticles (AgNPs) have shown great potential as therapeutic agents due to their ability to cause apoptotic cell death in cancer cells.
VEGF↓, suppressing the VEGF signaling pathway, repressing p53-mediated pathways, promoting cell cycle arrest,
P53↓,
TumCCA↑,
ROS↑, we found that AgNPs induced ROS generation
AntiTum↑, AgNPs exhibit similar antitumoral effects on both A549 and A549/DDP-bearing mice.
eff↑, AgNPs are internalized by cells far more effectively than free Ag+ under identical exposure conditions
ATP↓, AgNPs exposure also decreased basal respiration (52.3 ± 4.6 pmol/min/106 cells), maximal respiration (109.2 ± 12.2 pmol/min/106 cells), ATP production (
eff↑, These results explain why AgNPs remain effective against cisplatin-resistant A549 cells.
CTR1↑, recent studies have shown that AgNPs treatment significantly upregulates CTR1

4549-

AgNPs,

Silver nanoparticles: Synthesis, medical applications and biosafety

Review,

Var,

Review,

Diabetic,

ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier

4542-

AgNPs,

Silver Nanoparticles (AgNPs): Comprehensive Insights into Bio/Synthesis, Key Influencing Factors, Multifaceted Applications, and Toxicity─A 2024 Update

Review,

NA,

AntiCan↑, cytotoxicity against human colon carcinoma (HT-29) cells. The MTT assay confirmed their anticancer potential, with an IC50 value of 150.8 μg/mL.
DNAdam↑, Ag-NPs, accumulating in the nucleus, may cause genotoxicity, DNA damage, and chromosomal aberrations
ATP↓, Ag-NP exposure disrupts calcium homeostasis, leading to mitochondrial dysfunction, ATP depletion, and apoptosis.
Apoptosis↑,
ROS↓, induce cytotoxicity through numerous mechanisms viz., oxidative stress, mitochondrial dysfunction, DNA damage, cell cycle arrest, and subsequent apoptosis.
TumCCA↑,
*Bacteria↓, effectiveness as an antibacterial agent.
*BMD↑, Bone Repair Applications

373-

AgNPs,

Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116

in-vitro,

Colon,

HCT116

LDH↓, Increased lactate dehydrogenase leakage (LDH),
ROS↑,
MDA↑,
ATP↓,
GSH↓,
MMP↓, loss of

2287-

AgNPs,

Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine

in-vitro,

Nor,

HUVECs

*TumCP↓, AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability
*ROS↑, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes
*eff↓, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.
*MDA↑, exposure to AgNPs increased MDA levels and decreased GSH levels.
*GSH↓,
*MMP↓, significantly reduced both MMP and ATP levels (Fig. 7) in HUVECs,
*ATP↓,
*LC3II↑, expression levels of LC3-II and p62 were significantly increase
*p62↑,
*Bcl-2↓, the anti-apoptotic protein expression level of Bcl-2 in HUVECs decreased, while the pro-apoptotic protein expression levels of Bax and Caspase-3 increased significantly.
*BAX↑,
*Casp3↑,

5165-

AL,

The human allicin-proteome: S-thioallylation of proteins by the garlic defence substance allicin and its biological effects

in-vitro,

AML,

Jurkat

in-vitro,

Nor,

L929

necrosis↑, Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades.
Thiols↓, Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects.
GSH↓,
ENO1↓, allicin caused inhibition of enolase activity, an enzyme considered a cancer therapy target.
Zn2+↑, Allicin leads to Zn2+ release in murine EL-4 cells
Glycolysis↓, suggests that allicin can inhibit glycolysis which provides electron donors for ATP generation required for cellular biosynthesis pathways and growth of the cells.
ATP↓,
BioAv↓, achieving therapeutically relevant concentrations of allicin via the oral route is therefore unlikely and more direct routes of application to the desired site of action need to be considered

3434-

ALA,

Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

tumCV↓, significant dose-dependent reduction in cell viability, with the half-maximal inhibitory concentration (IC50) of LA to be 3.2 mM for MCF-7 cells and 2.9 mM for MDA-MB-231 cells
PI3K↓, LA significantly inhibited PI3K, p-AKT, p-p70S6K and p-mTOR levels
p‑Akt↓,
p‑P70S6K↓,
mTOR↓,
ATP↓, LA markedly reduced both ATP levels and glucose uptake (Fig. 4A and 4B). LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
GlucoseCon↓,
ROS↑,
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
LDHA↓,
Glycolysis↓,
ChemoSen↑, LA enhances chemosensitivity of spheroids to Dox treatment

3436-

ALA,

Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel

in-vitro,

BC,

MCF-7

ChemoSen↑, LA also enhanced the sensitivity of breast cancer spheroids to doxorubicin (Dox), demonstrating a synergistic effect.
PI3K↓, LA inhibits PI3K/AKT signaling in breast cancer spheroids
Akt↓,
ATP↓, found that LA markedly reduced both ATP levels and glucose uptake
GlucoseCon↓,
ROS↑, LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
Glycolysis↓,
CSCs↓,
IGF-1R↓, LA inhibits IGF-1R via furin downregulation, synergizes with other anticancer drugs like paclitaxel and cisplatin, and enhances radiosensitivity in breast cancer
Furin↓,
RadioS↑,

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↓,

1349-

And,

Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction

in-vitro,

Lung,

H460

33.16 μM

in-vitro,

Lung,

H1650

32.45 μM

TumCG↓,
TumMeta↓,
Ferroptosis↑,
ROS↑,
MDA↑,
Iron↑,
GSH↓, lipid ROS reduced glutathione (GSH) accumulation
GPx4↓,
xCT↓, SLC7A11
MMP↓,
ATP↓,

1536-

Api,

Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells

in-vitro,

MM,

MSTO-211H

0, 10, 30, and 50 µM) of apigenin for 48 h and 72 h

in-vitro,

MM,

H2452

tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

591-

Api,

doxoR,

Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

in-vitro,

AML,

Jurkat

in-vitro,

AML,

THP1

ATP↓,
Casp3↑,
γH2AX↑,

206-

Api,

Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress

in-vitro,

Lung,

H1299

 20 uM

in-vitro,

Lung,

H460

in-vitro,

Lung,

A549

 40 uM

in-vitro,

CRC,

HCT116

in-vitro,

Melanoma,

A375

in-vitro,

Lung,

H2030

in-vitro,

CRC,

SW480

Glycolysis↓, glucose consumption, lactate production, and ATP production were all strongly decreased by apigenin
lactateProd↓,
PGK1↓,
ALDOA↓,
GLUT1↓, Apigenin reduces GLUT1 expression levels.
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,
ROS↑, Apigenin causes oxidative stress leading to apoptosis. Because apoptotic signal transduction cascades involving caspase-9, -3 and PARP cleavage can be activated by increased ROS levels
Apoptosis↑,
eff↓, Cancer cells expressing high levels of GLUT1 are resistant to apigenin-induced apoptosis through metabolic compensation of glucose utilization.
NADPH↓, apigenin significantly decreased glucose utilization through suppression of GLUT1 expression, and consequently decreased NADPH production, which led to increased ROS levels.
PPP↓, inhibition of the PPP

566-

ART/DHA,

2DG,

Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells

in-vitro,

Lung,

A549

in-vitro,

Lung,

PC9

GlucoseCon↓,
ATP↓,
lactateProd↓,
p‑S6↓,
mTOR↓,
GLUT1↓,
Casp9↑,
Casp8↑,
Casp3↑,
Cyt‑c↑,
AIF↑,
ROS↑, generation of ROS is critical for the toxic effects of DHA

2388-

Ash,

Withaferin A decreases glycolytic reprogramming in breast cancer

in-vitro,

BC,

MDA-MB-231

5 μM WA

in-vitro,

BC,

MDA-MB-468

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-453

GlucoseCon↓, WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2.
lactateProd↓,
ATP↓,
Glycolysis↓,
GLUT1↓,
HK2↓,
PKM2↓,
cMyc↓, WA decreases the protein expression of key glycolytic enzymes via downregulation of c-myc expression
Warburg↓, WA decreases protein expression of key glycolytic enzymes and Warburg effect via c-myc inhibition
cMyc↓,

5173-

Ash,

2DG,

Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MDA-MB-468

in-vitro,

BC,

T47D

autoF↓, WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells.
lysosome↓, WFA treatment inhibits lysosomal activity
TumAuto↑, WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion.
p‑LDH↓, WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion
ATP↓, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation.
AMPK↑,
eff↑, WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells.
TumCG↓, WFA inhibits breast cancer growth and increases intracellular autophagosomes and autophagy markers
CTSD↓, we found that WFA impaired the maturation of Cathepsin D (CTSD)
CTSB↓, Inhibition of CTSD maturation also indicated reduced CTSB and CTSL activity as they are essential for the cleavage of CTSD.
CTSL↑,
cl‑PARP1↑, WFA and 2-DG treatment also showed higher cleavage of PARP1 in breast cancer cells
LDHA↓, WFA treatment effectively reduces the expression of LDHA in breast cancer cells
TCA↓, d leads to insufficient substrates for TCA cycle,

5362-

AV,

Anti-cancer effects of aloe-emodin: a systematic review

Review,

Var,

AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

1395-

BBR,

Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation

in-vitro,

GC,

20, 50, and 80 µM

Apoptosis↑,
ROS↑,
MMP↓,
ATP↓,
AMPK↑,
TP53↑,
p‑MAPK↓, decreased phosphorylated-MAPK3/1 expression
p‑ERK↓,

1379-

BBR,

Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells

in-vitro,

lymphoma,

TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

2707-

BBR,

Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway

in-vitro,

Liver,

HepG2

concentrations >25 µM after 48 h

in-vitro,

BC,

MCF-7

GLUT1↓, BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1
Akt↓, and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines
mTOR↓,
ATP↓, BBR-induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation
GlucoseCon↓,
TumCP↓,
Warburg↓, antineoplastic effect of BBR may involve the reversal of the Warburg effect
selectivity↑, The results demonstrated that the colony-forming capacity was slightly inhibited in Hs 578Bst normal breast cells following BBR treatment, but significantly inhibited in both cancer cell lines.
TumCCA↑, BBR effectively induced cell cycle arrest at the G2M phase
Glycolysis↓, Notably, our preliminary experiments identified that BBR strongly decreased the glucose uptake ability of HepG2 and MCF7 cell lines, therefore, it was hypothesized that BBR may interfere with tumor progression by inhibiting glycolysis.

2686-

BBR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Nor,

Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,

932-

BBR,

The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity

in-vivo,

Nor,

Rat liver

*glucoNG↓, These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis
*Glycolysis↑,
*NH3↑, inhibited ammonia detoxification
*NADPH/NADP+↑,
*ATP↓,
*toxicity↑, narrow margin between the expected benefits and toxicity

2735-

BetA,

Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications

Review,

Var,

mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-ÎºB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-ÎºB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2778-

Bos,

Development, Analytical Characterization, and Bioactivity Evaluation of Boswellia serrata Extract-Layered Double Hydroxide Hybrid Composites

in-vitro,

Nor,

*ATP↓, this extract is largely composed of terpene substances that are known to be able to bind to the membrane, thus causing the formation of irreversible pores, and they can lower protein synthesis, reducing ATP consumption
*ROS↓, well-known scavenger ability of the boswellic acids [49,50] was expected to significantly reduce the amount of the cytotoxic oxygen- and nitrogen-derived (ROS)

5849-

CAP,

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Review,

Var,

TRPV1↑, TRPV1 belongs to the transient receptor potential channel vanilloid subfamily and is also known as the capsaicin receptor and vanilloid receptor 1 (VR1).
Ca+2↑, The activation of TRPV1 induces the cellular influx of Ca2+ and Na+ ions 17-19, and the excess intracellular Ca2+ and Na+ leads to cell death 20.
TumCD↑,
TumCCA↑, Induced cell cycle arrest in G0/G1 phase and apoptosis by activating p53 to upregulate Fas/CD95 in TRPV1-overexpressing cells
Apoptosis↑,
P53↑,
Fas↑,
PI3K↑, Activated PI3K and p44/42 MAPK pathways to suppress ceramide production and increased androgen receptor expression
AR↑,
STAT3↓, attenuating STAT3 phosphorylation
ROS↑, Induced apoptosis by producing ROS originating from the mitochondria
MMP↓, Disrupted mitochondrial membrane potential and suppressed ATP synthesis to induce apoptosis
ATP↓,
CHOP↑, Stimulated ROS generation, increased CHOP expression level, and promoted apoptosis
TumCMig↓, As TRPV1 serves as the main Ca2+-influx channel, it is reasonable to suggest that TRPV1 could act as an enhancer or inhibitor of migration and invasion in a tissue- or cell-specific manner.
Twist↓, Capsaicin downregulated Tiwst1, Snail1, MMP2, and MMP9 and upregulated E-cadherin
Snail↓,
MMP2↓,
MMP9↓,
E-cadherin↑,

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↓,

2014-

CAP,

Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells

in-vitro,

PC,

Bxpc-3

150uM

in-vitro,

Nor,

HPDE-6

150uM

normal pancreatic epithelial cells were resistant to the effects of capsaicin.

in-vivo,

PC,

AsPC-1

mice orally fed with 2.5 mg/kg capsaicin

mice, 2.5 mg/kg capsaicin was given to mice by oral gavage, which is 0.202 mg/kg when converted to human equivalent dose (HED) and equates to 13.2 mg dose of capsaicin for a 60 kg person

ROS↑, ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells
*ROS∅, but not in normal HPDE-6 cells
selectivity↑, only small ~1.2fold ROS increase in normal cell
compI↓, capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity
compIII↓, and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively
eff↑, which was attenuable by SOD, catalase and EUK-134.
selectivity↑, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells
ATP↓, ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells
Cyt‑c↑, release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential
Casp9↑,
Casp3↑,
MMP↓,
SOD↓, mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls
GSH/GSSG↓, mice orally fed with 2.5 mg/kg capsaicin
Apoptosis↑, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
*toxicity∅, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
GSH↓, Taken together, our results suggest that depletion of GSH level and inhibition of SOD, catalase and GPx by capsaicin disturbs the cellular redox homeostasis resulting in increased oxidative stress.
Catalase↓,
GPx↓,
Dose↝, 13.2 mg dose of capsaicin for a 60 kg person

5819-

CBD,

The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence

Review,

Lung,

Apoptosis↑, Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress.
PPARγ↓,
mtDam↑,
ROS↑, Induced cell death via apoptosis and increased ROS levels.
EMT↓, It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity.
CD8+↑,
NK cell↑,
ChemoSen↑, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
ATP↓, CBD decreases intracellular ATP and glucose levels
glucose↓,
Ca+2↑, CBD enhances calcium influx (mediated by TRPV2) and elevates p-ERK expression in CIK cells
TRPV2↑,

5954-

CEL,

The molecular mechanisms of celecoxib in tumor development

Review,

Var,

TumCP↓, Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis
TumCMig↓,
TumCI↓,
COX2↓,
p‑NF-kB↓, thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
Akt↓,
MMP2↓,
MMP9↓,
Apoptosis↑, celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy.
mitResp↑,
ER Stress↑,
TumAuto↑,
ChemoSen↑, Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.
Inflam↓, NSAIDs achieve anti-inflammatory effects by inhibiting the activity of the inflammatory factor COX-2 and the synthesis of PGE2.
PGE2↓,
chemoPv↑, Numerous studies have confirmed that NSAIDs also have chemopreventive effects on tumors.
toxicity↓, Compared with other NSAIDs, celecoxib shows lower toxicity side effects (such as the most common gastrointestinal bleeding and gastric ulcer).[
Risk↓, Early studies have shown that celecoxib can effectively reduce the incidence of colorectal cancer, especially inhibiting the development of familial adenomatous polyposis to colorectal cancer.
PI3K↓, celecoxib can promote cancer cell apoptosis by inhibiting the signal pathway of 3-phosphoinositide-dependent kinase-1 and downstream protein kinase B (Akt) in human colon cancer cells.
RadioS↑, celecoxib enhances the sensitivity of cancer cells to radiation therapy
TumCMig↓, inhibits cancer cell migration and invasion by inhibiting the activity of C-Jun amino-terminal kinase and downregulating the expression of specific protein 1.
TumCI↓,
cJun↓,
Sp1/3/4↓,
ROS↑, Celecoxib targets mitochondria and promotes the release of ROS by significantly increased oxidative stress.
MMP↓, lead to the decrease of cell consumption and mitochondrial transmembrane potential (△ ψ m), increasing mitochondrial membrane permeability to promote the release of ROS
MPT↑,
Ca+2↑, promote Ca2+ influx, produce a higher pro-oxidation state, increase the accumulation of ROS in cancer cell mitochondria,
Glycolysis↓, inhibits the glycolysis process, ATP synthesis is significantly reduced, leading to cancer cell death.[
ATP↓,
CSCs↓, In addition to cancer cells, celecoxib can also inhibit CSCs.
Wnt/(β-catenin)↓, celecoxib can inhibit the transduction of Wnt/β-catenin signaling pathway
EMT↓, celecoxib can inhibit the process of EMT
toxicity↝, ong-term use increases the risk of hypertension among participants who already have cardiovascular risk factors.[

6009-

CGA,

Chlorogenic Acid: An In-Depth Review of Its Effectiveness in Cancer Treatment

Review,

Var,

TumCCA↑, CGA exerts potent anticancer effects through immunomodulation, induction of programmed cell death (PCD), cell cycle regulation, inhibition of tumor invasion and metastasis, suppression of angiogenesis, modulation of oxidative stress,
TumCI↓,
TumMeta↓,
angioG↓,
ROS↑, CGA exerts pro-oxidant effects within tumor cells in a concentration-dependent manner.
ChemoSen↑, and enhancement of chemotherapy efficacy. Boosting Chemotherapy Effectiveness of CGA
BioAv↓, its clinical applicability is often limited by its pharmacokinetic properties, including poor lipophilicity, low permeability, short half-life, and low oral bioavailability.
Half-Life↓,
PI3K↓, CGA suppresses the PI3K/Akt/mTOR cascade, increasing the Bax/Bcl-2 ratio and triggering apoptosis
Akt↓,
mTOR↓,
Apoptosis↑,
NOTCH↓, In non–small-cell lung cancer, it suppresses Notch pathway activity to induce apoptosis
Hif1a↓, CGA inhibits angiogenesis both in vitro and in vivo by suppressing HIF-1α expression and Akt phosphorylation, leading to reduced VEGF secretion
VEGF↓,
Casp3↑, In leukemia cells (U937, CML), CGA triggers caspase-3 activation, mitochondrial depolarization, and Bcr-Abl phosphorylation downregulation, culminating in apoptosis
MMP↓,
Ferroptosis↑, enhance bioavailability and sustain ROS generation, promoting ferroptosis in lymphoma and other malignancies [
ATP↓, combination of caffeine and CGA regulates mitochondrial function and ATP production, specifically targeting breast cancer mitochondria.

2781-

CHr,

PBG,

Chrysin a promising anticancer agent: recent perspectives

Review,

Var,

PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

1593-

Citrate,

Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?

in-vitro,

GC,

BGC-823

10mM

in-vitro,

GC,

SGC-7901

PFK↓, citrate, a strong physiological inhibitor of phosphofructokinase (PFK)
Glycolysis↓, citrate is a strong inhibitor of glycolysis
tumCV↓, 10 mM citrate led to a nearly complete disappearance of cancer cells, and after 72 h, no cells remained viable whatever the concentration used
cl‑Casp3↑,
cl‑PARP↑,
Apoptosis↑,
ATP↓, depletion of ATP generated by citrate
ChemoSen↑, In the previous study, citrate sensitized the cells to cisplatin, a drug which was poorly efficient by itself on such cells
Mcl-1↓, In the current study, citrate reduced MCL-1 expression in both the gastric cancer lines in a dose-dependent manner, in agreement with previous observations in mesothelioma cells
glucoNG↑, citrate activates neoglucogenesis by enhancing fructose 1,6-bisphosphatase activity
FBPase↑,
OXPHOS↓, When citrate is abundant in cells, this usually means that energy production (ATP) is sufficient, so oxidative phosphorylation (OXPHOS) and the Krebs cycle are slowed down or stopped.
TCA↓, Krebs cycle are slowed down or stopped.
β-oxidation↓, concomitantly inhibits β-oxidation
HK2↓, It may inhibit HK, at least indirectly, by the physiological retroaction of glucose-6-phosphate (G6P) on HK
PDH↓, citrate may inhibit pyruvate dehydrogenase (PDH) (39), the enzyme of the Krebs cycle which links glycolysis and the tricarboxylic cycle
ROS↑, citrate could also promote the formation of reactive oxygen species (ROS) since a sudden elevation of citrate concentration inside the cell might immediately stimulate the Krebs cycle.

1583-

Citrate,

Extracellular citrate and metabolic adaptations of cancer cells

Review,

NA,

Warburg↓, hypothesis that extracellular citrate might play a major role in cancer metabolism and is responsible for a switch between Warburg effect and OXPHOS
OXPHOS↓,
Dose∅, 10 mM citrate, cancer cells were shown to have decreased proliferation, ATP synthesis,
TumCP↓,
ATP↓,
eff↑, increased apoptosis and sensitivity to cis-platin
Apoptosis↑,
TumCG↓, high doses of citrate in vivo decreased tumour growth
PFK1↓, increased levels of cytosolic citrate taken up from the extracellular space would decrease phosphofructokinase-1 (PFK-1) activity

1587-

Citrate,

ATP citrate lyase: A central metabolic enzyme in cancer

Review,

NA,

ACLY↓, administration of citrate at high level mimics a strong inhibition of ACLY and could be tested to strengthen the effects of current therapies. -a strong ACLY inhibition could be mimicked by by flooding the cytosol with citrate.
other↓, ACLY inhibition by simple drugs such as HCA or bempedoic acid should be tested, optimally associated with glycolytic inhibitors (or glucose starvation diet) and current therapies.
PFK1↓, citrate promotes: - the inactivation of PFK1 and decreases ATP production [
ATP↓,
PFK2↓, inhibition of PFK2 in ascite cancer cells
Mcl-1↓, deactivation of the anti-apoptotic factor Mcl-1 and the activation of caspases such as caspase 2, 3 and 9
Casp3↑,
Casp2↑,
Casp9↑,
IGF-1R↓, downregulation of the IGF-1R/PI3K/AKT
PI3K↓,
Akt↓,
p‑Akt↓, decreased phosphorylation of AKT and ERK in non-small cell lung cancer
p‑ERK↓,
PTEN↑, activation of PTEN suppressor,
Snail↓, reversion of dedifferentiation (in particular through Snail inhibition with E-cadherin expression) and stimulation of T lymphocytes response
E-cadherin↑,
ChemoSen↑, increasing the sensitivity of tumors to cisplatin

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

2315-

Citrate,

Why and how citrate may sensitize malignant tumors to immunotherapy

Review,

Var,

Bcl-2↓, SCT can induce silent apoptosis by reducing expression of key pro-apoptotic proteins (Bcl-2, surviving, MCL1), and promoting the activation of caspases-3 and −9 and −8, as showed in multiple cancer cell lines
Mcl-1↓,
survivin↓,
Casp3↑,
Casp9↑,
Ferroptosis↑, SCT can also trigger ferroptosis, an iron-dependent form of lytic cell death inducing lipid peroxidation (LPO)
lipid-P↑,
Ca+2↓, citrate lowers mitochondrial Ca2+ concentration by chelation
Akt↓, by chelating cytosolic Ca2+, citrate inhibits the Ca2+/CAMKK2/AKT/mTOR signaling pathway, thereby suppressing HIF1-α dependent glycolysis
mTOR↓,
Hif1a↓,
MCU↓, reduces the activity of the mitochondrial calcium uniporter (MCU), resulting in decreasing ATP production, increasing ROS production
ATP↓,
ROS↑,
eff↑, Of note, ferroptosis can enhance the effectiveness of immunotherapy, as showed in glioma models

1601-

Cu,

The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress

in-vitro,

CRC,

i-CRT↓, Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD (immunogenic cell death)
ICD↑,
i-ATP↓,
i-HMGB1↓,
ER Stress↑, accumulation of ROS and inducing ERS
ROS↑,
DCells↑, promoted the maturation of dendritic cells (DCs)
CD8+↑, and activation of CD8+T cells
IL12↑, secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ)
IFN-γ↑,
TGF-β↓, while downregulating transforming growth factor-β (TGF-β) levels

Showing Research Papers: 1 to 50 of 126
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 126

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 2,
Total Targets: 276

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Catalase↑, 1, GPx↑, 1, GSH↓, 1, MDA↓, 1, MDA↑, 1, NADPH/NADP+↑, 1, ROS↓, 2, ROS↑, 1, ROS∅, 1, SOD↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↓, 3, MMP↓, 1,

Core Metabolism/Glycolysis ⓘ

glucoNG↓, 1, glucose↓, 1, Glycolysis↑, 1, NH3↑, 1,

Cell Death ⓘ

BAX↑, 1, Bcl-2↓, 1, Casp3↑, 1,

Autophagy & Lysosomes ⓘ

LC3II↑, 1, p62↑, 1,

Migration ⓘ

TumCP↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

eff↓, 1, eff↑, 1,

Clinical Biomarkers ⓘ

BMD↑, 1,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, Bone Healing↑, 1, hepatoP↑, 1, neuroP↑, 1, toxicity↑, 1, toxicity∅, 1, Wound Healing↑, 1,

Infection & Microbiome ⓘ

AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 2,
Total Targets: 37

Scientific Paper Hit Count for: ATP, Adenosine triphosphate

11 3-bromopyruvate
9 Vitamin C (Ascorbic Acid)
6 Berberine
6 Shikonin
5 Silver-NanoParticles
5 Citric Acid
5 salinomycin
4 Graviola
3 2-DeoxyGlucose
3 Alpha-Lipoic-Acid
3 Apigenin (mainly Parsley)
3 Capsaicin
3 Propolis -bee glue
3 Metformin
3 Quercetin
3 Sulforaphane (mainly Broccoli)
3 Silymarin (Milk Thistle) silibinin
3 Ursolic acid
2 Radiotherapy/Radiation
2 Ashwagandha(Withaferin A)
2 Copper and Cu NanoParticles
2 diet FMD Fasting Mimicking Diet
2 Galloflavin
2 Honokiol
2 Magnetic Fields
2 Pachymic acid
2 Phenethyl isothiocyanate
2 Resveratrol
2 Thymoquinone
1 Sorafenib (brand name Nexavar)
1 cetuximab
1 Auranofin
1 Allicin (mainly Garlic)
1 Andrographis
1 doxorubicin
1 Artemisinin
1 Aloe anthraquinones
1 Betulinic acid
1 Boswellia (frankincense)
1 Cannabidiol
1 Celecoxib
1 Chlorogenic acid
1 Chrysin
1 Curcumin
1 Docosahexaenoic Acid
1 Chemotherapy
1 Disulfiram
1 EGCG (Epigallocatechin Gallate)
1 Emodin
1 Electrical Pulses
1 Hyperthermia
1 Ivermectin
1 Luteolin
1 Methylene blue
1 Melatonin
1 immunotherapy
1 Magnesium
1 Methylglyoxal
1 Pterostilbene
1 Rosmarinic acid
1 SonoDynamic Therapy UltraSound
1 triptolide
1 Arsenic trioxide
1 Vitamin K2
1 γ-Tocotrienol

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

ATP Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

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 ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Autophagy & Lysosomes ⓘ

Migration ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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