toxicity Cancer Research Results
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Scientific Papers found: Click to Expand⟱
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↑,
eff↑, novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum.
TumCG↓, Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity.
TumMeta↓,
toxicity↝,
Glycolysis↓, The anticancer effects of 3BP were initially attributed to inhibition of glycolysis (Ganapathy-Kanniappan et al., 2009;
toxicity↓, Our previous work demonstrated that microencapsulation of 3BP reduces its toxicity (Chapiro et al., 2014).
Dose↝, we were only able to reliably deliver multiple doses of the drug intravenously (i.v.), and the number of injections and time periods over which we could administer the drug were limited.
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].
toxicity↑, German police took action on 4 August after two patients from the Netherlands and one from Belgium died shortly after undergoing treatment at the Biological Cancer Centre, run by alternative practitioner Klaus Ross in the town of Brüggen, Germany
Glycolysis↓, It is believed to "starve" tumor cells to death by inhibiting glycolysis, the breakdown of glucose molecules to provide cells with energy.
eff↑, experiments on human cancer cell lines showed that combining another chemotherapeutic with 3BP increased its efficacy.
OS↑, the patient "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↑,
toxicity↝, Vogl says doctors should "absolutely" not perform systemic infusions, in which the drug circulates through the entire body. "
*Dose↑, A 3-year-old, male neutered Labrador Retriever, weighing 28.2 kg, presented to the emergency department ... after ingesting a human supplement containing 200 mg of 5-HTP. The amount of 5-HTP ingested was estimated between 980 and 1988mg
*toxicity↝, At presentation, the dog demonstrated progressive neurologic abnormalities consistent with serotonin syndrome, including altered mentation and ataxia.
*BioAv↑, By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT
*Dose↝, he tolerability and subjective effects of oral 5-HTP at 100, 200 and 300 mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge.
*toxicity↝, Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100 mg.
*5HT↑, 5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-tryptophan (L-Trp).
*toxicity↝, The use of L-Trp as a dietary supplement was discontinued in 1989 due to an outbreak of eosinophilia-myalgia syndrome (EMS) that was traced to a contaminated synthetic L-Trp from a single manufacturer.
*toxicity↓, However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for last 20 years, with the possible exception of one unresolved case of a Canadian woman.
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*5HT↑, 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis.
*Inflam↓, 5-HTP also suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators
*memory↑, figure 10
*Sleep↑, In a group of children with sleep terrors, treatment with 5-HTP was able to modulate the arousal level and to induce a long-term improvement of sleep terrors [1
*Weight↓, The effect of 5-HTP on feeding behavior, mood state, and weight loss was studied. 5-HTP promoted decreased food intake and weight loss as well as typical anorexia-related symptoms without changes in mood state during the period of observation
*DNAdam↓, 5-HTP significantly reduced tert-butylhydroperoxide-induced oxidative damage in human fibroblast cells and protected these cells against oxidative DNA damage
*ROS↓, By acting as a reactive oxygen species (ROS) scavenger, 5-HTP has the potential for use in the treatment of inflammatory diseases and as an analgesic
*toxicity↝, An excess of 5-HTP may be responsible for serotonin syndrome (see Section 8.2.1) and an excessive treatment was found to be associated with severe side effects, including behavioral disturbances, abnormal mental functions, and intolerance.
*toxicity↝, Interestingly, our patient’s supplement did not contain L-tryptophan but instead had 5-HTP. There have been several reports of 5-HTP associated EMS. Michelson et al8 reports a case of family members who became ill with EMS and eosinophilia after expo
*toxicity↝, The L-5-HTP was found to have an impurity and once it was replaced without the impurity, the eosinophilia resolved, suggesting the impurities in L-5-HTP may have been related to the development of EMS
*toxicity↝, The serotonin syndrome (SS) is a clinical condition resulting from serotonergic over-activity at synapses of the central and peripheral nervous systems.
*toxicity↝, A 9-month-old female Labrador retriever was evaluated after ingestion of a 5-HTP supplement. Signs of agitation developed within 1 h of ingestion
*toxicity↝, Treatment included fluid therapy, a mannitol constant rate infusion, antiemetics, gastroprotectants, and cyproheptadine as a serotonin antagonist. The patient responded well to treatment and was discharged within 48 h of presentation.
*toxicity↝, Ingestion of 5-HTP in dogs can result in a potentially life-threatening syndrome resembling serotonin syndrome in humans, which requires prompt and aggressive care
*5HT↑, The reported mechanism of action of 5-HTP is through an increase of serotonin concentrations within the CNS,1
*Dose↝, The lowest dose at which signs developed was 23.6 mg/kg (10.7 mg/lb); death was reported for 3 dogs at 128, 131.9, and 287 mg/kg (58.2, 60, and 157.7 mg/lb), respectively
*toxicity↝, The eosinophilia—myalgia syndrome is a newly recognized illness that has been associated with the consumption of tryptophan products. It is not known whether the cause is related to the tryptophan itself or to chemical constituents introduced by the
*toxicity↝, The outbreak of the eosinophilla—myalgia syndrome in 1989 resulted from the ingestion of a chemical constituent that was associated with specific tryptophan-manufacturing conditions at one company.
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BC, |
MDA-MB-231 |
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Nor, |
MCF10 |
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Paraptosis↑, We show here that 4~5 µM AF induces paraptosis, a non-apoptotic cell death mode characterized by dilation of the endoplasmic reticulum (ER) and mitochondria, in breast cancer cells.
ER Stress↑,
TrxR↓, covalent inhibition of thioredoxin reductase (TrxR)
selectivity↑, subtoxic doses of AF and Bz induced paraptosis selectively in breast cancer cells, sparing non-transformed MCF10A cells
toxicity↝, whereas 4~5 μM AF killed both cancer and MCF10A cells
ROS↑, We found that treatment with 5 μM AF very weakly and transiently increased ROS levels at 2~4 h and then again at 24 h
mt-TrxR1↓, AF inhibits cytosolic and mitochondrial TrxR (TrxR1 and TrxR2), two selenoenzymes for the Trx pathway [3]
mt-TrxR2↓,
*Dose?, Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days.
*Half-Life↝, The mean gold maximum concentration in plasma (Cmax) at day 7 was 0.312 μg/ml and the half-life (t1/2) 35 days, so steady-state blood levels would not be reached in short-term therapy.
*Dose↑, The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC50) for E. histolytica and 4× that for Giardia, was in feces at 7 days.
*toxicity↝, Long-term (months to years) auranofin therapy was linked to side effects, including diarrhea (40% of subjects), skin rashes (2% to 5%), hematologic abnormalities (rare), and proteinuria (5%)
*Bacteria↓, Higher doses of auranofin will clearly be required for some infections.
*Dose↑, The FDA has approved clinical trials using auranofin at up to 21 mg/day for treatment of relapsed chronic lymphocytic leukemia after daily doses of 9 and 12 mg for at least 28 days were well tolerated
*Bacteria↓, strong antibacterial, anticancer, anti-inflammatory, and wound-healing properties.
AntiCan↑,
*Inflam↓,
*Wound Healing↑,
eff↑, Cytotoxic effects of anticancer drugs such as verapamil, cisplatin, carmustine, and methotrexate are improved by citrate-coated silver oxide NP
ChemoSen↑,
EGFR↓, silver (AgNPs), gold (AuNPs), and superparamagnetic iron oxide nanoparticles (SPIONPs) have shown the
ability to interfere with EGFR
ROS↑, In MCF-7 breast cancer cells, AgNP induced ROS activated proteins, such as p53, Bax, and caspase-3, cause programmed cell death
P53↑,
BAX↑,
Casp3↑,
toxicity↝, AgNPs produce ionic silver and ROS that have
antibacterial properties, but their non-specific absorption
can harm healthy cells.
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BC, |
BT549 |
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MDA-MB-231 |
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MCF10 |
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TumCD↑, Our findings provide additional support for proteotoxic stress as a mechanism by which AgNPs selectively kill TNBCs
selectivity↑,
*toxicity↝, Failure to separate dissolved silver cations (Ag+) from AgNPs before toxicity testing likely contributes to the lack of a definitive answer. Ag+ is highly toxic and has a distinct cytotoxic mechanism of action compared to AgNPs;
Dose↝, doses in the range of 4–6 mg/kg delivered systemically for multiple weeks induced therapeutic responses
OS↑, 40 patients were injected intravenously with 1.8 mg of AgNPs for 3 consecutive days (combined with standard COVID-19 treatments), and the group receiving AgNPs had significantly greater survival rate
TumCD↑, IC50 values of the AgNPs, AuNPs and Ag/AuNPs on HepG2 cells were determined as 38.42 μg ml-1, 43.25 μg ml-1 and 39.20 μg ml-1
TumVol↓, tumour reduction (∼45 to 65%) was observed in the nanoparticle-treated animal
*toxicity↝, The No-Observed-Adverse-Effect-Level (NOAEL) for the AgNPs was determined to be 2000 mg per kg of body weight (bw) from an acute toxicity test.
hepatoP↑, (Ag/AuNPs) for hepatoprotective activity against diethylnitrosamine (DEN)-induced liver cancer in a Sprague Dawley (SD) rat model
toxicity↝, The effect of Ag ions was also investigated and compared with that of AgNPs, as it is anticipated that Ag ions will be released from AgNPs, which may be responsible for their toxicity.
tumCV↓, Cell viability tests indicated high sensitivity of Jurkat T cells when exposed to AgNPs compared to Ag ions
ROS↑, AgNPs and Ag ions induce similar levels of cellular reactive oxygen species during the initial exposure period and; after 24 h, they were increased on exposure to AgNPs compared to Ag ions, which suggest that oxidative stress may be an indirect caus
p38↑, AgNPs exposure activates p38 mitogen-activated protein kinase through nuclear factor-E2-related factor-2 and nuclear factor-kappaB signaling pathways, subsequently inducing DNA damage, cell cycle arrest and apoptosis.
NRF2↓,
NF-kB↝,
DNAdam↑,
Apoptosis↑,
*toxicity↝, As the liver is one of the largest accumulation and deposition sites of circulatory AgNPs, it is important to evaluate the hepatotoxicity induced by AgNPs
selectivity↑, cancerous liver cells were generally more sensitive than the normal liver cells.
mt-ROS↑, mitochondrial ROS has been identified as one of the causes of AgNPs-induced hepatotoxicity
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Colon, |
HCT116 |
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Nor, |
NCM460 |
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*Bacteria↓, Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles
ROS↑, intracellular reactive oxygen species (ROS) increased
p‑p38↑, Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax.
BAX↑,
Bcl-2↓, Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax/Bcl-2 ratio and activation of P21, further accelerating cell death
BAX↑,
P21↑,
TumCD↑,
toxicity↝, low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 μg/mL will cause oxidative damage to colon cells.
TumVol↓, incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA
TNF-α↓, TNF-α, IL-6 and IL-1β these cytokines were found to be downregulated after treatment with AgNP-MSA
IL6↓,
IL1β↓,
*toxicity↝, liver sections were found to have normal architecture in all treated groups except those treated at the 9 and 10 mg/kg b.w. doses
TumCG↓, treatment with AgNPs, the logistic growth of the tumor incidence was significantly lower (
selectivity↑, MSA-AgNPs aggregated instantly in response to the acidic extracellular pH of solid tumors, leading to greatly enhanced uptake by cancer cells
selectivity↑, Because the particle size in the study was approximately 10 nm, any AgNP that escaped entry into the tumor microenvironment and entered the systemic circulation was effectively cleared from the body.
Weight↑, AgNP-MSA not only inhibited the tumor incidence but also helped to overcome the progressive body weight loss of tumor-bearing mice.
ROS↑, anticancer property demonstrated by AgNP can be attributed to this increase in oxidative stress in the tumor microenvironment.
NO↑, AgNPs significantly increased the oxygen free radical and NO levels in the tumor microenvironment, which oppose hypoxia.
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CRC, |
HCT116 |
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HEK293 |
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NRF2↑, Nanosilver increased Nrf2 protein expression and disrupted the cell cycle at the G1 and G2/M phases.
TumCCA↑, AgNPs interact with DNA to stop
the cell cycle and lead to apoptosis
ROS↑, Nanosilver induced significant mitochondrial oxidative stress in HCT116, whereas it did not in the non-cancer HIEC-6 and nanosilver/sodium ascorbate co-treatment was preferentially lethal to HCT116 cells,
selectivity↑,
*AntiViral↑, AgNPs are effective antiviral agents against various viruses such as human
immunodeficiency virus, hepatitis B virus, and monkey pox virus through interaction with
surface glycoproteins on the virus
*toxicity↝, Citrate and PVP-coated AgNPs have been found to be less toxic than non-coated AgNPs
ETC↓, AgNPs affects mitochondrial function through the disruption of the electron transport
chain2,24,26,33,39–41
MMP↓, Studies have shown that exposure to AgNPs resulted in a decrease of mitochondrial membrane potential (MMP) in various in vitro and in vivo experiments
DNAdam↑, AgNPs has also been shown to interact with and induce damage to DNA, DNA strand breaks, DNA damage
Apoptosis↑, apoptosis induced by AgNPs were through membrane lipid peroxidation, ROS, and oxidative stress
lipid-P↑,
other↝, Several studies have showed AgNPs interact with various proteins such as haemoglobin, serum albumin, metallothioneins, copper transporters, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), and bacterial proteins.
UPR↑, Studies have shown exposure to AgNPs induces activation of the UPR
*GRP78/BiP↑, AgNPs induced increased levels of GRP78, phosphorylated PERK, phosphorylated eIF2-α, and
phosphorylated IRE1α, spliced XBP1, cleaved ATF-6, CHOP, JNK and caspase 12
*p‑PERK↑,
*cl‑eIF2α↑,
*CHOP↑,
*JNK↑,
Hif1a↓, One study showed AgNPs inhibits HIF-1 accumulation and suppresses expression of HIF-1 target genes in breast cancer cells (MCF-7) and also found the protein
levels of HIF-1α and HIF-1β decreased
AntiCan↑, Many studies have shown that ascorbic acid, on its own, has anti-cancer effects
*toxicity↓, However, when the rats were treated with both ascorbic acid
and AgNPs, a decrease in toxic effects was observed in non-cancer parotid glands in rats
eff↑, Studies have shown both AgNPs and ascorbic acid have greater effects and toxicity in
cancer cells relative to non-cancer cells
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RAW264.7 |
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*Wound Healing↑, unique antimicrobial properties silver nanocrystallites have garnered substantial attention and are used extensively for biomedical applications as an additive to wound dressings, surgical instruments and bone substitute materials.
*eff↝, cytotoxicity was dependent on various factors such as surface charge and coating materials used in the synthesis, particle aggregation, and the cell-type for the different silver nanoparticles that were investigated.
*toxicity↝, uncoated or colloidal silver nanoparticles were found to be the least toxic to both macrophage and lung epithelial cells
*AntiAg↑, n the present study we show that nanosilver has an innate antiplatelet property and effectively prevents integrin-mediated platelet responses, both in vivo and in vitro, in a concentration-dependent manner
*Bacteria↓, We have recently reported synthesis of highly stable, uniformly sized silver nanoparticles endowed with enhanced antibacterial properties.
*Dose↝, Nanoparticles were spherical in shape, 10-15nm in diameter and monodispersed
*Dose↝, The extent of inhibition was the same irrespective of whether platelets were aspirinized or not. More than 80% (n $ 10) inhibition in amplitude was recorded at a nanoparticle concentration of 50 uM, which also reduced the slope of agregation/min
*Dose↝, (2!8 mg/kg body weight) in two different mice strains led to significant inhibition of platelet aggregation in mouse whole blood (studied by electronic impedance) in a dose-dependent manner
*toxicity↝, a dose of nanosilver up to 300 mg/kg was nontoxic to rodents.
*DNAdam↑, AgNPs induced 8-oxoG, double strand breaks (DSBs), chromosomal damage, and DNA deletions in both genotypes
*toxicity↝, In summary, citrate-coated AgNPs are genotoxic in both genotypes and Ogg1 deficiency exacerbates the effect ( 4 mg/kg of citrate-coated AgNPs over a period of 7 d.)
eff↝, data suggest that humans with genetic polymorphisms and mutations in OGG1 may have increased susceptibility to AgNP-mediated DNA damage.
*VEGF↓,
*IL1↓, IL-1β-induced permeability
toxicity↝, Since low concentrations of Ag-NP were found to be non-toxic
other↝, Our results indicate that Ag-NP have a therapeutic benefit in vascular permeability.
*Dose↝, The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. 5 to 12 nm
*eff↑, Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin.
*RenoP↑, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid.
*antiOx↑, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content.
*MDA↓,
*NO↓,
*hepatoP↑, hepatoprotective effect of Ag NPs may be attributed to their antioxidant properties
*toxicity↝, The Ag NPs dose is 1/10 of LD50, which is 5.5 mg/kg.
*GSH↑, GSH, SOD, GST, and CAT of the septic group. Meanwhile, the Ag NPs-treated mice showed a significant (p < 0.05) increase in all four parameters.
*SOD↑,
*GSTs↑,
*Catalase↑,
toxicity↝, generally well tolerated. Eleven adverse events of grade 1 or grade 2 severity were observed. No grade 3 or grade 4 adverse events were observed.
hepatoP↓, Elevation of liver enzymes (5/11) and skin rash (2/11) was the most common adverse events.
BioAv↓, However, WA appears to have low oral bioavailability.
Apoptosis↑, WA has been reported to induce apoptosis via intrinsic and extrinsic pathways in human prostate, breast and leukemic cancer cells among others
ROS↑, It has also shown the ability to induce apoptosis in osteosarcoma U2OS cell lines by generating ROS, also causing cell cycle arrest in osteosarcoma cell lines by inhibition of G2/M checkpoint proteins
TumCCA↑,
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Melanoma, |
B16-F10 |
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Dose↝, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. 223 nm
TumCG↓, In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs
TumCP↓, AP has been found to inhibit the cell proliferation and DNA synthesis of various cancer cells, including breast, colon, glioblastoma, skin, and brain cancer cells (Naidu, 2003a).
BioAv↓, AP is limited due to its water insolubility, rapid degradation (accelerated by metal ions and/or light), and low bioavailability.
BioAv↑, Therefore, new technologies including nanoparticles that can enhance its delivery efficacy and reduce the dose of administration for Vc while not reducing its anti-cancer efficacy are highly desired.
other↑, These results conformed to the conclusion that only high doses of ascorbic acid have the ability to induce cancer cell death.
Apoptosis↑, Conclusively, the AP/PTX-SLNs exhibited a greater efficacy in inducing cell apoptosis by reducing the Bcl-2/Bax ratio accompanied by promoting tubulin polymerization
Bax:Bcl2↑,
EPR↑, such nanocarriers to permeate into tumor sites because of the enhanced permeation and retention (EPR) effect.
toxicity↝, AP/PTX synergistic combination-based SLN therapy did not induce toxicity and represents a promising strategy for paclitaxel/the vitamin C derivative in promoting anti-cancer effects.
*Dose↝, Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones.
*toxicity↝, lethal dose (LD50) in Swiss albino mice was 120.65 mg/kg.
tumCV↓, Aloe vera whole-leaf material caused a dose-dependent decrease in the viability in HeLa and HepG2 cells
*AntiAg↑, Aloe vera have antiplatelet effects,
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BC, |
MCF-7 |
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HUVECs |
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toxicity↝, We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein.
ChemoSen↑, Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells.
selectivity↑, Surprisingly, low concentrations of baicalin and baicalein had a greater effect on MCF-7 viability. A
Apoptosis↑, Induction of Apoptosis and Necrosis by Baicalin and Baicalein Used alone and in Combination with Anticancer Drugs
necrosis↑,
MMP↓, After treatment with baicalin and baicalein at high concentrations (IC50), the ΔΨm of cancer cells was diminished to 30% of the control value
DNAdam↑, DNA Damage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
cl‑PARP↑, PARP Cleavage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
MRP1↓, Moreover, baicalin and baicalein reduced cisplatin resistance by inhibiting the expression of genes involved in drug resistance, such as MRP1 [30] and Bcl-2, and via the Akt/mTOR and Nrf2/Keap 1 pathway [26].
Bcl-2↓,
hepatoP↑, baicalin and baicalein can also help decrease the side effects of cisplatin treatment by protecting the liver from damage [31]
cardioP↑, Similar to baicalein, baicalin also significantly protects against doxorubicin’s cardiotoxicity.
BioAv↝, This is because baicalein has a smaller size and high lipophilicity, contributing to fast absorption and an improved ability to penetrate cells [60].
BioAv↓, BA is greatly hindered by its poor water solubility, low bioavailability, and off-target toxicity
toxicity↝,
BioAv↑, nanoparticles, liposomes, micelles, and nanofibers, aiming to improve its solubility and bioavailability, prolong plasma half-life, and enhance targeting ability, thereby augmenting its anti-cancer efficacy
Half-Life↑,
NRF2↓, Brusatol is a potent Nrf2 inhibitor for future cancer treatment.
TumCG↓, Brusatol exhibits significant tumor inhibition in multiple cancers.
ChemoSen↑, also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents
ROS↑, Graphical Abstract
NF-kB↓,
Akt↓,
mTOR↓,
TumCCA↑,
Apoptosis↑,
PARP↑,
Casp↑,
P53↓,
Bcl-2↓,
PI3K↓,
JAK2↓,
EMT↓,
p27↑,
ROCK1↓,
MMP2↓,
MMP9↓,
NRF2↓, which is the reason why brusatol is called an Nrf2 inhibitor [15]. Brusatol is a potent Nrf2 inhibitor
AntiTum↑, Brusatol shows significant antitumor effects in vitro and in vivo
HO-1↓, Moreover, brusatol inhibited the expression of Nrf2 downstream genes, such as HO-1 [19], [31], [32], NQO1 [43], [44], VEGF [45], and AKR1C1 [46].
NQO1↓,
VEGF↓,
MRP1↓, brusatol reduced both the mRNA and protein levels of NQO1, HO-1, MDR1, and MRP5
RadioS↑, Improvement of sensitivity to radiotherapy and phototherapy
PhotoS↑,
toxicity↝, the toxicity of brusatol is a problem that can not be ignored.
Dose↝, Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose.
toxicity↝, injection of BromAc into mucinous tumours had a manageable safety profile.
eff↑, An objective response to treatment was seen in 73·2% of treated sites.
AntiCan↑, Borneol is a multifaceted anticancer agent with intrinsic cytotoxic activity;
Apoptosis↑, via diverse mechanisms such as apoptosis induction, mitochondrial dysfunction, ROS generation
mtDam↑,
ROS↑,
mTORC1↓, and inhibition of oncogenic pathways, including mTORC1/eIF4E/HIF-1α, NF-κB, STAT3, and PI3K/Akt.
EIF4E↓,
Hif1a↓,
NF-kB↓,
STAT3↓,
PI3K↓,
Akt↓,
ChemoSen↑, borneol demonstrates significant synergistic effects when combined with established chemotherapeutic agents like temozolomide, doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil,
BioEnh↑, enhancing drug uptake, overcoming resistance, and amplifying apoptosis, especially in drug-resistant and brain tumor models.
BioAv↑, borneol possesses high intestinal absorption, BBB permeability, moderate toxicity, and compliance with Lipinski's Rule of Five.
BBB↑,
toxicity↝,
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*eff↑, L-borneol has better potential in cerebrovascular diseases.
*eff↑, D-borneol exhibits better antitumour sensitizing effects than L-borneol.
*toxicity↝, Synthetic borneol is less safe. Synthetic borneol is widely used because of its advantages of low cost and easy availability.
*Inflam↓, It has anti-inflammatory, analgesic, antipyretic, antibacterial, neuroprotective, and permeation-promoting effects.
*Bacteria↓,
*neuroP↑,
*Half-Life↝, oral administration. It reaches its highest concentration in 30 min, and its half-life is 18 h
*BBB↑, and can easily pass through the BBB and blood–ocular barrier (BOB).
*BioEnh↑, Borneol can promote the absorption and affect the distribution of other drugs, which is beneficial for reducing the dosage, prolonging the action time, and improving the curative effects of these drugs
*P-gp↓, inhibitory activity against P-gp is as follows: L-borneol > D-borneol ≈ synthetic borneol.
*CYP3A4↓, inhibition of intestinal CYP3A4 would improve the bioavailability of drugs.
*ROS↓, and reduce the rate of cerebral oedema and the volume of infarcts by inhibiting oxidative stress
*neuroP↑, neuroprotective effects of the three kinds of borneol are as follows: L-borneol > synthetic borneol > D-borneol
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vitro+vivo, |
BC, |
T47D |
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- |
in-vitro, |
BC, |
MCF10 |
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AntiTum↓, Carnosic acid (CA) exerts an anti‐tumor effect via generating ROS or activating the mitochondria‐related apoptosis pathway in vitro and in vivo.
ROS↑, CA promoted cancer cell apoptosis via ROS generation, which activated c‐Jun N‐terminal kinase (JNK) and p38 phosphorylation.
cJun↑, CA Activated JNK and p38 in Breast Cancer Cell Lines
p‑p38↑,
Apoptosis↑, CA induced apoptosis of hepatocellular carcinoma cells via the reactive oxygen species (ROS)‐mediated mitochondrial pathway
ROS↑,
eff↑, Furthermore, the combined application of CA and curcumin suppressed the proliferative activity and disrupted the mitochondrial function of metastatic prostate cancer cells compared with their individual uses
TumCP↓, CA Inhibited Breast Cancer Proliferation and Glucose Uptake
glucose↓, Glucose consumption was accelerated by low concentrations of CA, but decreased with increasing time and CA concentration.
BAX↑, up‐regulating Bax and PARP and down‐regulating Bcl‐2.
PARP↑,
Bcl-2↓,
eff↓, We then abrogated the effect of CA‐induced ROS using the antioxidant NAC (5 mM).
Ki-67↓, These findings indicated that CA could accelerate tumor apoptosis by up‐regulating Bax expression and down‐regulating Ki67 and Bcl‐2 in vivo.
toxicity↝, Furthermore, CA did not injure vital organs.
STAT3↓, CA has been reported to suppress the STAT3 signaling pathway through ROS generation and inhibit the phosphoinositide 3‐kinase/Akt/mTOR signaling pathway in colon cancer and lung cancer
PI3K↓,
Akt↓,
mTOR↓,
Pain↓, It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams.
BioAv↓, clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties.
toxicity↝, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting.
toxicity↓, The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.
eff↑, The non-pungent capsaicin analogs arvanil and olvanil display improved anti-invasive activity relative to capsaicin in human SCLC cells.
AMPK↑, Furthermore, the anti-invasive activity of arvanil, olvanil and capsaicin was mediated by the AMPK pathway.
toxicity↝, These adverse side effects of capsaicin have led patients to abandon taking the drug
BioAv↑, Arvanil and olvanil were selected because they are orally available, non-pungent, and have comparable pharmacological activity profile, relative to capsaicin.
TRPV1↑, Arvanil and olvanil bind to TRPV1 with higher affinity than capsaicin.
TumCI↓, Capsaicin displays anti-invasive activity in human SCLC cells
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in-vitro, |
BC, |
MCF-7 |
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- |
in-vitro, |
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MDA-MB-231 |
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eff↑, The thymol/carvacrol mixture demonstrated superior cytotoxicity (IC50 = 0.92–1.70 µg/mL) and increased selectivity compared to cisplatin,
selectivity↑, with high selectivity indices (144.88–267.71).
BioAv↝, The bioavailability score for both thymol and carvacrol is 0.55, indicating moderate bioavailability
BBB↑, The blood–brain barrier (BBB) permeability values are 1.82 for thymol and 1.99 for carvacrol, indicating that both compounds have moderate permeability across the BBB.
*toxicity↝, carvacrol may be slightly less toxic than thymol. Both compounds have a predicted toxicity class of 4, indicating moderate toxicity.
*antiOx↑, This remarkable synergy in antioxidant activity
COX2↓, carvacrol and thymol showed considerable outcomes, their mixture proved more effective in suppressing COX-2.
5LO↓, synergistic effect observed with the thymol/carvacrol mixture, particularly pronounced for 5-LOX and COX-2 inhibition
DNAdam↑, It is generally agreed that DNA is the preferential and cytotoxic target for cisplatin and other platinating agents. able to induce similar numbers of single-strand and double-strand breaks on DNA
ER Stress↑, shown to cause activation of apoptotic caspases through activation of the endoplasmic reticulum (ER) stress pathway (
UPR↑, When the ER experiences stress such as starvation or treatment with inhibitors of N-glycosylation (e.g. tunicamycin), it cannot fold or transport proteins correctly, and the UPR is activated.
ATF4↑, regulatory components of the ER stress pathway, including ATF4, ATF6, XBP1, and BiP (Grp78), are upregulated
ATF6↑,
XBP-1↑,
GRP78/BiP↑,
NP/CIPN↝, Carboplatin is notably less neurotoxic than cisplatin at conventional doses, with a similar sensory neuropathy occurring in approximately 6% of patients
toxicity↝, Carboplatin rarely results in nephrotoxicity and peripheral neuropathy, with its major toxicity being myelosuppression
eff↑, exposure to buthiomine sulfoximine (BSO), which significantly depleted cellular glutathione concentration, resulted in a significant enhancement in cisplatin cytotoxicity [151].
TrxR1⇅, Both cisplatin and transplatin show this inhibition of TxrR1 [161], as does oxaliplatin but not carboplatin [162]
Dose↑, The maximum-tolerated dose was 4.2 g/m(2) once daily or 1.0 g/m(2) three times daily.
toxicity↝, Oral GTE at the doses studied can be taken safely for at least 6 months.
Dose↝, UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily
*DNArepair↑, Uncaria tomentosa (Ut, Cat's claw) has antioxidant properties [10] and can stimulate DNA repair [11] and myelopoiesis
toxicity↝, Treatment with Ut did not alter liver function, defined as elevation of liver enzymes (alanine aminotransferase-ALT, aspartate aminotransferase-AST, γ glutamyl transpeptidase-GGT), and bilirubin levels, and kidney function
BioAv↝, consider the fact that all CRC patients in the present study underwent colectomy, which could interfere with the absorption of Ut.
eff∅, Ut at dose 300 mg dry extract daily is not effective in reducing the most prevalent adverse events due to treatment with 5FU/Leucovorin and oxaliplatin in patients with advanced CRC.
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.[
Apoptosis↑, apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side‑effects in normal cells
TumCMig↓,
*toxicity↝, toxic at higher doses and the recommended dose for chrysin is <3 g/day
ChemoSen↑, chrysin also inhibits multi‑drug resistant proteins and is effective in combination therapy
*BioAv↓, extremely low bioavailability in humans due to rapid quick metabolism, removal and restricted assimilation. The bioavailability of chrysin when taken orally has been estimated to be between 0.003 to 0.02%
Dose↝, safe and effective in various studies where volunteers have taken oral doses ranging from 300 to 625 mg without experiencing any documented effect
neuroP↑, Chrysin has been shown to exert neuroprotective effects via a variety of mechanisms, such as gamma-aminobutyric acid mimetic properties, monoamine oxidase inhibition, antioxidant, anti-inflammatory and anti-apoptotic activities
*P450↓, Chrysin inhibits cytochrome P450 2E1, alcohol dehydrogenase and xanthine oxidase at various dosages (20 and 40 mg/kg body weight) and protects Wistar rats against oxidative stress
*ROS↓,
*HDL↑, ncreased the levels of high-density lipoprotein cholesterol, glutathione S-transferase, superoxide dismutase and catalase
*GSTs↑,
*SOD↑,
*Catalase↑,
*MAPK↓, inactivate the MAPK/JNK pathway and suppress the NF-κB pathways, and at the same time upregulate the expression of PTEN, and activate the VEGF/AKT pathway
*NF-kB↓,
*PTEN↑,
*VEGF↑,
ROS↑, chrysin treatment in ovarian cancer led to the augmented generation of reactive oxygen species, a decrease in MMP and an increase in cytoplasmic Ca2+,
MMP↓,
Ca+2↑,
selectivity↑, It has been found that chrysin has no cytotoxic effect on normal cells, such as fibroblasts
PCNA↓, Chrysin likewise downregulates proliferating cell nuclear antigen (PCNA) expression in cervical carcinoma cells
Twist↓, Chrysin decreases the expression of TWIST 1 and NF-κB and thus suppresses epithelial-mesenchymal transition (EMT) in HeLa cells
EMT↓,
CDKN1C↑, Chrysin administration led to the upregulation of CDKN1 at the transcript and protein leve
p‑STAT3↑, Chrysin decreased the viability of 4T1 breast cancer cells by suppressing hypoxia-induced phosphorylation of STAT3
MMP2↓, chrysin-loaded PGLA/PEG nanoparticles modulated TIMPS and MMP2 and 9, and PI3K expression in a mouse 4T1 breast tumor model
MMP9↓,
eff↑, Chrysin used alone and as an adjuvant with metformin has been found to downregulate cyclin D and hTERT expression in the breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
CLDN1↓, CLDN1 and CLDN11 expression have been found to be higher in human lung squamous cell carcinoma. Treatment with chrysin treatment reduces both the mRNA and protein expression of these claudin genes
TumVol↓, Treatment with chrysin treatment (1.3 mg/kg body weight) significantly decreases tumor volume, resulting in a 52.6% increase in mouse survival
OS↑,
COX2↓, Chrysin restores the cellular equilibrium of cells subjected to benzopyrene by downregulating the expression of elevated proteins, such as PCNA, NF-κB and COX-2
eff↑, quercetin and chrysin together decreased the levels of pro-inflammatory molecules, such as IL-6, -1 and -10, and the levels of TNF via the NF-κB pathway.
CDK2↓, Chrysin has been shown to inhibit squamous cell carcinoma via the modulation of Rb and by decreasing the expression of CDK2 and CDK4
CDK4↓,
selectivity↑, chrysin selectively exhibits toxicity and induces the self-programed death of human uveal melanoma cells (M17 and SP6.5) without having any effect on normal cells
TumCCA↑, halting the cell cycle at the G2/M or G1/S phases
E-cadherin↑, upregulation of E-cadherin and the downregulation of cadherin
HK2↓, Chrysin decreased expression of HK-2 in mitochondria, and the interaction between HK-2 and VDAC 2 was disrupted,
HDAC↓, Chrysin, a HDAC inhibitor, caused cytotoxicity, and also inhibited migration and invasion.
Risk↓, CoQ10, an essential compound for cellular energy production, is often found at low levels in cancer patients, suggesting a link between CoQ10 deficiency and cancer risk
TumCG↓, Research shows CoQ10 helps fight cancer by slowing tumor growth, preventing new blood vessel formation in tumors and triggering self-destruction of abnormal cells
angioG↓,
TumCD↑,
*toxicity↓, The compound helps regulate immune function and inflammation by supporting
mitochondrial health and enhancing T-cell activity, while showing minimal side effects
even at high doses
*BioAv↑, Simple steps, like splitting doses and pairing CoQ10 with a meal containing fats, aid in its
absorption and effectiveness
MMPs↓, reported ability of CoQ10 to suppress something known
as MMPs (matrix metalloproteinases)
Inflam↓, A further aspect focused on the anti-inflammatory effects of CoQ10
chemoP↑, Some individuals received
significant help in diminishing tumor markers, while others used CoQ10 to mitigate drug
side effects.
cardioP↑, According to the authors, coenzyme Q10 shows evidence
of lowering that heart strain.
*ROS↓, Researchers explained that coenzyme Q10 is a compound naturally made in your body,
essential for mitochondrial energy production and normal oxidative processes
*toxicity↝, Liver enzyme elevation has been reported after prolonged use of doses of
300 milligrams (mg) daily, but this effect did not escalate into overt liver damage.
Dose?, If you have never taken CoQ10 before, aim for 200 mg to 300 mg daily for the first three weeks. After about 21 days, step down to 100 mg daily
*toxicity↝, The toxicity of Cu overload is known to be due, in part, to the release of ROS via the Fenton or Haber-Weiss reaction, causing lipid, protein, DNA, and RNA damage
ROS↑, Cu-induced ROS can induce lipid peroxidation, which raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic.
lipid-P↓,
HNE↑, raises hydroxynonenal (HNE) levels and causes lipid peroxidation to become toxic
MAPK↑, Cu exposure causes an elevation in intracellular ROS levels, which then stimulates the MAPK signaling pathway, increasing JNK/SAPK and p38 homologous activity and phosphorylation levels
JNK↑, Cu-induced ROS continuously activate JNK, promote the production of the AP-1 transcription factor, increase Beclin 1 and Atg7 production, and cause autophagy and apoptosis in tumor cells
AP-1↑,
Beclin-1↑,
ATG7↑,
TumAuto↑,
Apoptosis↑,
HO-1↑, Fang and colleagues consistently found that Cu activates the ROS/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase-1 (NQO1) signaling cascade to induce autophagy
NQO1↑,
mt-ROS↑, Cu NPs induce complete autophagy by enhancing mitochondrial ROS production and inducing autophagy
Fenton↑, generating large amounts of ROS and oxygen via a Fenton-like reaction
TumCD↑, Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and p
Apoptosis↓,
ROS↑,
angioG↑,
Cupro↑,
Paraptosis↑,
eff↑, copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy.
eff↓, Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes
selectivity↑, Copper nanoparticles also can selectively attack cancer cells and spare healthy cells
This selectivity is attributed to the EPR effect, which enables nanoparticles to accumulate in tumor tissue by exploiting leaky blood vessels
DNAdam↑, Copper has been found to induce DNA damage and oxidation through the formation of ROS.
eff↑, Tumor cells suffering from oxygen deficiency often have an increased concentration of CTR-1, which facilitates the transport of copper(I) into the cells
eff↑, The results demonstrate the promising capabilities of 64CuCl2 as a valuable tool for both diagnosis and therapy in various types of cancer
eff↑, nanoparticles have remarkable properties, including a large surface area to volume ratio, excellent compatibility with living organisms, and the ability to generate ROS when exposed to an acidic tumor microenvironment
eff↑, Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy (CDT)
Fenton↑, CDT is a promising treatment strategy for cancer that utilizes the in situ Fenton reaction, which is activated by endogenous substances, such as GSH and H2O2 without the need for external energy input
H2O2↑, Copper-based substrates have been developed that generate H2O2 internally and function effectively in weakly acidic tumor microenvironments (TME)
eff↑, metal peroxide nanomaterials and offers a promising strategy to improve CDT efficacy
eff↑, Copper nanoparticles can also be used in phototherapy
eff↑, Copper nanoparticles have also shown success in destroying cancer tissue by hyperthermia. This method is a local anticancer treatment in which cells are exposed to high temperatures.
RadioS↑, promising results when used in combination with radiotherapy or chemotherapy for various tumor types.
ChemoSen↑,
eff↑, copper nanoparticles are promising in cancer immunotherapy because they enhance immune-based therapies
*toxicity↝, Copper is a necessary trace mineral for the human body, but high concentrations of copper can be toxic
other↑, Extensive research has shown that cancer cells require an increased copper content to support their rapid growth compared to normal cells
eff↑, Copper nanoparticles can be used to generate heat when exposed to certain wavelengths of light or alternating magnetic fields.
Glycolysis↓, DCA redirects mitochondrial metabolism away from glycolysis to OXPHOS by the inhibition of PDKs
OXPHOS↑,
PDKs↓,
ROS↑, DCA increases reactive oxygen species (ROS), which induce downstream changes in mitochondrial function, causing the selective apoptosis of cancer cells.
Apoptosis↑,
GlucoseCon↓, treatment with DCA decreased glucose consumption and lactate production in vitro in a manner that was statistically significant compared to the controls
lactateProd↓,
RadioS↑, it enhanced the sensitivity of A549 and H1299 cells to X-ray-induced cell killing
TumAuto↑, DCA has been shown to induce autophagy instead of inhibiting it.
mTOR↓, The DCA-induced induction of autophagy was found to be mediated by the generation of ROS, the inhibition of the mammalian targets of rapamycin (mTOR),
LC3s↓, Lu and colleagues found that LC3 decreased while p62 levels increased, both of which are hallmarks of autophagy inhibition
p62↑,
TumCG↓, In vivo studies have demonstrated that DCA inhibits the growth of A549 and H1975 tumor xenografts and enhances the survival of tumor-bearing nude mice
OS↑,
toxicity↝, the most clinically limiting side effect of DCA is peripheral neuropathy
ChemoSen↑, DCA exerts synergistic potential with the most widely used chemotherapy agent, paclitaxel, on NSCLC cells.
eff↑, DCA has also been shown to have anticancer synergies with various non-traditional agents, the most prominent of which is metformin.
eff↑, Another compound that DCA has been shown to have a strong synergism with is ivermectin.
Ferritin↓, SAL and its derivatives prevent the movement of iron from the lumen to the cytosol, triggering an iron-depletion reaction that is characterized by the rapid degradation of ferritin
CSCs↓, SAL has been shown to selectively target CSCs in vitro and in vivo, but its mode of action is not fully understood.
EMT↓, SAL has also been shown to suppress the epithelial–mesenchymal transition (EMT) as well as transforming growth factors (TGFs). EMT is a process that is pivotal to metastasis.
ROS↑, SAL triggers apoptosis by elevating intracellular ROS levels, leading to the translocation of Bax protein to the mitochondria, cytochrome c (Cytc) release, and the activation of caspase-3
Cyt‑c↑,
Casp3↑,
ER Stress↑, SAL was observed to upregulate ER stress-related proteins in a time-/dose-dependent manner
selectivity↑, SAL induced cell death in multiple apoptosis-resistant cancer cell lines, but not in normal healthy human cells
eff↑, Skeberdytė and colleagues were among the first to recognize that DCA had synergistic potential with SAL.
TumCG↓, DCA and SAL were found to significantly suppress tumor growth in vivo in the mice.
Showing Research Papers: 1 to 50 of 85
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 85
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Fenton↑, 2, GSH↓, 1, H2O2↑, 1, HNE↑, 1, HO-1↓, 1, HO-1↑, 1, lipid-P↓, 1, lipid-P↑, 1, NQO1↓, 1, NQO1↑, 1, NRF2↓, 3, NRF2↑, 1, OXPHOS↑, 1, mt-OXPHOS↓, 2, ROS↑, 18, mt-ROS↑, 2, TrxR↓, 1, TrxR1⇅, 1, mt-TrxR1↓, 1, mt-TrxR2↓, 1,
Metal & Cofactor Biology ⓘ
Ferritin↓, 1,
Mitochondria & Bioenergetics ⓘ
ATP↓, 3, ETC↓, 1, mitResp↓, 1, mitResp↑, 1, MMP↓, 4, MPT↑, 1, mtDam↑, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 1, ATG7↑, 1, GAPDH↓, 1, glucose↓, 1, GlucoseCon↓, 1, GlutaM↓, 1, Glycolysis↓, 6, HK2↓, 2, lactateProd↓, 1, LDH↓, 1, PDH↓, 1, PDKs↓, 1, TCA↓, 1,
Cell Death ⓘ
Akt↓, 4, Apoptosis↓, 1, Apoptosis↑, 12, BAX↑, 4, Bax:Bcl2↑, 1, Bcl-2↓, 5, Casp↑, 1, Casp3↓, 1, Casp3↑, 2, Cupro↑, 1, Cyt‑c↑, 2, hTERT/TERT↓, 1, JNK↑, 1, MAPK↑, 1, Mcl-1↓, 1, necrosis↑, 1, p27↑, 1, p38↑, 1, p‑p38↑, 2, Paraptosis↑, 2, TRPV1↑, 1, TumCD↑, 5,
Kinase & Signal Transduction ⓘ
Sp1/3/4↓, 1,
Transcription & Epigenetics ⓘ
cJun↓, 1, cJun↑, 1, other↑, 2, other↝, 2, PhotoS↑, 1, tumCV↓, 2,
Protein Folding & ER Stress ⓘ
ATF6↑, 1, ER Stress↑, 4, GRP78/BiP↑, 1, UPR↑, 2, XBP-1↑, 1,
Autophagy & Lysosomes ⓘ
Beclin-1↑, 1, LC3s↓, 1, p62↑, 1, TumAuto↑, 3,
DNA Damage & Repair ⓘ
DNAdam↑, 5, P53↓, 1, P53↑, 1, PARP↑, 2, cl‑PARP↑, 1, PCNA↓, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 1, CDK4↓, 1, cycD1/CCND1↓, 1, P21↑, 1, TumCCA↑, 4,
Proliferation, Differentiation & Cell State ⓘ
CSCs↓, 2, EIF4E↓, 1, EMT↓, 4, HDAC↓, 1, mTOR↓, 3, mTORC1↓, 1, PI3K↓, 4, STAT3↓, 2, p‑STAT3↑, 1, TumCG↓, 7, Wnt/(β-catenin)↓, 1,
Migration ⓘ
5LO↓, 1, AP-1↑, 1, Ca+2↑, 2, CDKN1C↑, 1, CLDN1↓, 1, E-cadherin↑, 1, Ki-67↓, 1, MMP2↓, 3, MMP9↓, 3, MMPs↓, 1, ROCK1↓, 1, TumCI↓, 3, TumCMig↓, 3, TumCP↓, 3, TumMeta↓, 1, Twist↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 1, angioG↑, 1, ATF4↑, 1, EGFR↓, 1, EPR↑, 1, Hif1a↓, 2, NO↑, 1, VEGF↓, 1,
Barriers & Transport ⓘ
BBB↑, 2,
Immune & Inflammatory Signaling ⓘ
COX2↓, 3, IL1β↓, 1, IL6↓, 1, Inflam↓, 2, JAK2↓, 1, NF-kB↓, 2, NF-kB↝, 1, p‑NF-kB↓, 1, PGE2↓, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 4, BioAv↑, 4, BioAv↝, 3, BioEnh↑, 1, ChemoSen↑, 9, Dose?, 1, Dose↑, 1, Dose↝, 6, eff↓, 2, eff↑, 24, eff↝, 1, eff∅, 1, Half-Life↑, 1, MRP1↓, 2, RadioS↑, 4, selectivity↑, 13,
Clinical Biomarkers ⓘ
EGFR↓, 1, Ferritin↓, 1, hTERT/TERT↓, 1, IL6↓, 1, Ki-67↓, 1, LDH↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 3, AntiTum↓, 1, AntiTum↑, 1, cardioP↑, 2, chemoP↑, 1, chemoPv↑, 1, hepatoP↓, 1, hepatoP↑, 2, neuroP↑, 1, NP/CIPN↝, 1, OS↑, 5, Pain↓, 1, QoL↑, 2, Risk↓, 2, toxicity↓, 3, toxicity↑, 1, toxicity↝, 24, TumVol↓, 3, Weight↑, 1,
Total Targets: 177
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 2, Catalase↑, 2, GSH↑, 1, GSTs↑, 2, HDL↑, 1, MDA↓, 1, ROS↓, 4, SOD↑, 2,
Core Metabolism/Glycolysis ⓘ
CYP3A4↓, 1,
Cell Death ⓘ
JNK↑, 1, MAPK↓, 1,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, cl‑eIF2α↑, 1, GRP78/BiP↑, 1, p‑PERK↑, 1,
DNA Damage & Repair ⓘ
DNAdam↓, 1, DNAdam↑, 1, DNArepair↑, 1,
Proliferation, Differentiation & Cell State ⓘ
PTEN↑, 1,
Migration ⓘ
AntiAg↑, 2,
Angiogenesis & Vasculature ⓘ
NO↓, 1, VEGF↓, 1, VEGF↑, 1,
Barriers & Transport ⓘ
BBB↑, 1, P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
IL1↓, 1, Inflam↓, 3, NF-kB↓, 1,
Synaptic & Neurotransmission ⓘ
5HT↑, 3,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, BioAv↑, 2, BioEnh↑, 1, Dose?, 1, Dose↑, 3, Dose↝, 7, eff↑, 3, eff↝, 1, Half-Life↝, 2, P450↓, 1,
Functional Outcomes ⓘ
hepatoP↑, 1, memory↑, 1, neuroP↑, 2, RenoP↑, 1, Sleep↑, 1, toxicity↓, 3, toxicity↝, 29, Weight↓, 1, Wound Healing↑, 2,
Infection & Microbiome ⓘ
AntiViral↑, 1, Bacteria↓, 5,
Total Targets: 50
Scientific Paper Hit Count for: toxicity, toxicity
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#:1025 State#:% Dir#:4
wNotes=on sortOrder:rid,rpid
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