Dose Cancer Research Results
Dose, Dosage: Click to Expand ⟱
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Drug dosage vs efficacy, and actual dosage number of research papers.
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Scientific Papers found: Click to Expand⟱
Dose↓, The patient was given 9 doses of KAT (200 mg) over a period of 6 months
Remission↑, After treatment, the patient loses cancer and the tissue regenerates from 5% to 30%
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in-vitro, |
BC, |
MCF-7 |
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in-vitro, |
Nor, |
MCF10 |
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in-vitro, |
BC, |
MDA-MB-231 |
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in-vitro, |
BC, |
BT549 |
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in-vivo, |
BC, |
MDA-MB-231 |
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ROS↑, AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death.
DNAdam↑,
selectivity↑, We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages.
TumCG↓, reduce TNBC growth and improve radiation therapy.
RadioS↑,
Dose↝, s 23±14 nm: particles were diluted to 40 μg/mL. 25 μg/mL AgNP dilution for 24 hours. zeta potential of AgNPs in water at pH 7 was approximately −36 mV, indicating good colloidal stability.
selectivity↑, Depending on AgNP dose, all three TNBC cell lines were 5- to 10-fold more sensitive to AgNP exposure than the nontumorigenic breast cells.
other↝, this study demonstrate that the cytotoxicity was dependent on exposure of cells to intact AgNPs and not due to Ag+ ions
eff↓, toxicity of AgNPs was significantly reduced in MDA-MB-231, MCF-7, and MCF-10A cells following pretreatment with GSH
eff↑, Selective depletion of GSH by BSO resulted in increased AgNP toxicity in all cell lines.
γH2AX↑, AgNPs significantly increased γH2AX in these cells compared to radiation alone.
Dose↓, Strikingly, an AgNP dose of as little as 1 μg/mL resulted in a dose enhancement of IR treatment (approximately 2-fold at the 2 Gy dose) f
eff↑, Moreover, intratumoral injection of AgNPs with or without radiation treatment can inhibit the growth of TNBC xenografts in mice
OS↑, remission
Dose↓, Electron microscopy of AgNP solution revealed bimodal nanoparticle size
distribution: 3 and 12 nm.
BioAv↝, basal **silver ion** concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution.
toxicity↓, no toxicities were observed and he had complete radiographic resolution of his cancer
Remission↑,
other↝, patient serum was analyzed and intact nanoparticles were not identified. Thus, we could not isolate the circulating AgNP form
other↝, Analysis of urine showed no AgNP or detectable nanoparticle fragments
other↝, AgNP solution was also exposed to simulated gastric fluid, in which they aggregated into larger nanoparticles according to UV-Vis absorption.
Dose↝, GDH: based on repeat setup, estimated PPM is 20PPM assuming 67% effecient. 1.2mg/60mL (he took 160mL/day
BioAv↝, GDH: chatAI computed the estimated bioavailability at 7%
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Lung, |
A549 |
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BC, |
MCF-7 |
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in-vitro, |
BC, |
MDA-MB-231 |
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Dose↓, IC50 change from 33ug/mL(APG) to 2.4ug/mL(APG-NLC)
selectivity↑, higher selectivity from cancer to normal cell: see Table 4
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in-vitro, |
BC, |
MDA-MB-231 |
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in-vitro, |
BC, |
T47D |
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in-vitro, |
Nor, |
MCF10 |
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TumCD↑, Astaxanthin increases the melatonin-induced cell death in breast cancer cells
DNAdam↑, Astaxanthin-melatonin combination and DNA damages in breast cancer cells
*antiOx↑, strong anti-oxidative, anti-tumoral, and anti-inflammatory effects.
*AntiTum↑,
Inflam↓,
tumCV↓, Astaxanthin at lower doses than melatonin reduced cell viability and Bcl2 expression, induced apoptosis and DNA damage in MDA-MB-231 and T47D.
Bcl-2↓,
Apoptosis↓,
selectivity↑, Meanwhile, the effects of astaxanthin on cell cytotoxicity, apoptosis, and DNA damage in MCF10A cells are insignificant compared to MDA-MB-231 and T47D.
eff↑, Furthermore, the presence of astaxanthin increased the function of melatonin-induced cell death in breast cancer cells.
Dose↓, The results showed that very low doses of astaxanthin reduced survival rate, induced apoptosis, reduced the expression of Bcl2 proteins, and destroyed the DNA in cancerous cells
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↑,
Risk↓, higher calcium intake was consistently associated with reduced CRC risk across tumor sites and sources of calcium.
Dose↓, Mean (SD) total calcium intake was 401 mg/d (104 mg/d) for females and 407 mg/d (95 mg/d) for males in the lowest quintile (Q1)
eff↝, While our study found an inverse association of total and supplemental calcium intake with rectal cancer risk, we did not observe a statistically significant association with dietary calcium intake.
TCA↓, Citrate serves as a key metabolite in the tricarboxylic acid cycle (TCA cycle, also referred to as the Krebs cycle)
T-Cell↝, modulation of T cell differentiation
Glycolysis↓, Citrate directly suppresses both cell glycolysis and TCA.
PKM2↓, citrate also inhibits glycolysis via its indirect inhibition of PK
PFK2?, In addition, citrate can inhibit PFK2,
SDH↓, citrate can inhibit enzymes, such as succinate dehydrogenase (SDH) and pyruvate
dehydrogenase (PDH), in the TCA cycle
PDH↓,
β-oxidation↓, Citrate also inhibits β-oxidation as it promotes the formation of malonyl-CoA, which decreases the mitochondrial transport of fatty acids by inhibiting carnitine palmitoyl transferase I (CPT I)
CPT1A↓,
FASN↑, citrate has a positive role in promoting fatty acid synthesis
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Hif1a↓, Notably, in AML cell line U937, citrate induces apoptosis in a dose- and time-dependent manner by regulating the expression of HIF-1α and its downstream target GLUT-1
GLUT1↓,
angioG↓, citrate can also inhibit angiogenesis
Ca+2↓, chelate calcium ions in tumor cells
ROS↓, The other potential mechanism involved in citrate-mediated promotion of cancer growth and proliferation may be through its ability to decrease the levels of reactive oxygen species (ROS) in tumor cells
eff↓, dual effects of citrate in tumors may depend on the concentrations of citrate treatment, and different concentrations may bring out completely opposite effects even in the same tumor.
Dose↓, citrate concentration (<5 mM) appears to boost tumor growth and expansion in lung cancer A549 cells. 10mM and higher inhibited cell growth.
eff↑, citrate combined with ultraviolet (UV) radiation caused activation of caspase-3 and -9 in tumor cells (
Mcl-1↓, citrate has also been found to downregulate Mcl-1
HK2↓, Citrate also inhibits the enzymes PFK1 and hexokinase II (HK II) in glycolysis in tumor cells
IGF-1R↓,
PTEN↑, citrate may exert its effect via activating PTEN pathway
citrate↓, In addition to prostate cancer, citrate levels are significantly decreased in blood of patients with lung, bladder, pancreas and esophagus cancers
Dose∅, daily oral administration of citrate for 7 weeks at dose of 4 g/kg/day reduces tumor growth of several xenograft tumors and increases significantly the numbers of tumor-infiltrating T cells with no significant side effects in mouse models
eff↑, combining citrate with other compounds such as celecoxib, cisplatin, and 3-bromo-pyruvate, and have generated promising results
eff↑, combination of low effective doses of 3-bromo-pyruvate (3BP) (15uM), an inhibitor of glycolysis, and citrate (3 mM) significantly depleted the proliferation capability and migratory power of the C6 glioma
eff↑, Zinc treatment could lead to citrate accumulation in malignant prostate cells, which could have therapeutic potential in clinical therapy of prostate cancer.
eff↑, synergistic efficacy mediated by citrate combined with current checkpoint blockade therapies with anti-CTLA4 and/or anti-PD1/PDL1 will develop alternative novel strategies for future immunotherapy.
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BC, |
MCF-7 |
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in-vitro, |
BC, |
MDA-MB-231 |
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angioG↓, confirming its potential to inhibit angiogenesis in cancer
tumCV↓, The CuO NPs showed enhanced toxic effect at both time intervals when compared to that of sinapic acid alone.
Dose↓, The enhanced cytotoxicity observed at much lower concentrations such as 21.5 and 7.5 ug/mL for MCF7 and MDA-MB231
ROS↑, the cancer cells display an elevated level of oxidative stress with increase in the production of reactive oxygen species (ROS).
eff↑, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36
Dose↓, Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21
Risk↓, Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence
*Dose↓, Low intensity electric fields appear to enhance cell function.
Apoptosis↑, Here we focus on high electric fields that induce programmed cell death or apoptosis in cells and tumors in mice.
DNAdam↑, Mitochondria, and probably nucleus/DNA and membrane pump mechanisms, are intracellular targets that contribute to cell death.
mtDam↑,
*MusCon↓, All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues
*Dose↓, bursts of bipolar pulses with much smaller pulse widths (0.25–50 μs).
*eff↑, demonstrated that the H-FIRE pulse waveforms at 4000 V/cm did not cause muscle contractions in a rat model, nor did they cause a significant temperature increase.
*Temp↝, generate negligible temperature increase (Δ𝑇<1°C) during the whole pulse application procedure
MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,
*neuroP↑, multiple pharmacological functions, including neuroprotection.
*GSH↑, Hon attenuates the H2O2- or 6-hydroxydopamine (6-OHDA)-induced apoptosis of PC12 cells by increasing the glutathione level
*HO-1↑, and upregulating a multitude of cytoprotective proteins, including heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, thioredoxin 1, and thioredoxin reductase 1.
*NADPH↑,
*Trx1↑,
*TrxR1↑,
*NRF2↑, Hon promotes transcription factor Nrf2 nuclear translocation and activation.
*ROS↓, Hon is promising for further development as a therapeutic drug against oxidative stress-related neurodegenerative disorders. Inhibition of ROS accumulation
*antiOx↑, Upregulation of antioxidant species in PC12 cells
*BBB↑, Hon has the ability to cross the BBB
Dose↓, We demonstrated here that Hon, at the concentration as low as 5 μM, significantly
rescues the cells from H2O2- or 6-OHDA-induced oxidative damage
*Dose↓, Overall, <2% of US adults and ∼5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium).
*eff↑, potassium intake increases urinary excretion of sodium through action on the renal tubule
*BP↓, potassium intake of ≥4700 mg/d in adults optimally decreases the blood pressure response to sodium intake
ROS↑, exposure to high doses of carotenoids has a pro-oxidant effect
Dose↓, lycopene, an intake of 5 to 7 mg per day was recommended for healthy people to maintain the circulating levels of this carotenoid, in order to combat oxidative stress and prevent chronic diseases
Dose↑, higher concentrations of lycopene (35–75 mg/day) may be required when there is a disease, such as cancer and cardiovascular diseases.
antiOx↑, main protective effect of lycopene is due to its antioxidant effect through the inactivation of ROS and the extinction of free radicals
P450↓, significant decrease in cytochrome P450 2E1
TNF-α↓, TNF-α, IL-1β, and IL-12) were also found
IL1β↓,
IL12↓,
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HCC, |
HUH7 |
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in-vivo, |
HCC, |
NA |
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TumCG↓, Metronomic S-1 significantly inhibited tumor growth, which was enhanced by combination with vandetanib.
toxicity↓, With respect to toxicities, MTD S-1 caused severe body weight loss and myelosuppression, whereas metronomic S-1 did not cause any overt toxicities.
OS↑, Moreover, metronomic S-1 or metronomic S-1 with vandetanib prolonged survival, the latter treatment providing the greatest benefit.
TSP-1↑, whereas the expression of thrombospondin-1 was upregulated by metronomic S-1 and metronomic S-1 with vandetanib.
Dose↓, The IC50 levels for the MTD and metronomic schedule for Huh-7 cells were 3.84 and 0.77 µM, respectively
Dose↓, hepatoma cell lines, the metronomic schedule inhibited cell proliferation at approximately 1/2 to 1/4 concentrations of 5-FU compared with MTD schedule
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BC, |
4T1 |
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in-vitro, |
BC, |
MCF-7 |
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ChemoSen↑, PEMF therapy may enhance DOX cytotoxicity in breast cancer cells,
TRPC1↑, increased by TRPC1 overexpression,
Dose↓, PEMF exposure enhances DOX-mediated killing of breast cancer cells, reducing the IC50 value of DOX by half, whereas muscle cells, representative of collateral tissues, were less sensitive to PEMF-enhanced DOX-mediated cytotoxicity
selectivity↑, whereas muscle cells, representative of collateral tissues, were less sensitive to PEMF-enhanced DOX-mediated cytotoxicity.
ROS↑, Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells.
Apoptosis↑,
TumAuto↑,
TumCP↓, Nimbolide inhibits the proliferation of human pancreatic ductal adenocarcinoma cells
TumCMig↓, Nimbolide suppresses migration, invasion, EMT and anchorage-independent growth of pancreatic cancer cells
TumCI↓,
EMT↓,
Dose↓, All three pancreatic adenocarcinoma cell lines (HPAC, MIAPaCa-2 and PANC-1) tested were sensitive to the cytotoxic effects of nimbolide at a minimal dose of 3–5 μM
selectivity↑, Nimbolide was not highly toxic to normal pancreatic cells (hTERT HPNE) even at higher doses (10 μM).
Akt↓, Nimbolide treatment reduced the activation of AKT in pancreatic cancer cells.
eff↓, Moreover, inhibition of ROS with NAC eliminated the nimbolide-induced cell death,
BAX↑, in response to nimbolide, as did the elevated expression levels of Bax, cleaved caspase-3, and cleaved PARP and the reduced levels of Bcl-2.
cl‑Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Risk↓, strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer.
AntiCan↑, Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects.
TumCP↓, PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis
TumMeta↓,
ChemoSen↑, combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy
*BioAv↑, ITCs are released from glucosinolates by the action of the enzyme myrosinase. The enzyme myrosinase can be activated by cutting or chewing the vegetables, but heating can destroy its activity
*other↝, Although water cress and broccoli are known to be the richest source, PEITC can also be obtained from turnips and radish
*Dose↝, In a study conducted with human volunteers, approximately 2 to 6 mg of PEITC was found to be released by the consumption of one ounce of watercress
Dose↓, significant anti-cancer effects can be achieved at micromolar concentrations of PEITC.
*BioAv↑, PEITC is highly bioavailable after oral administration. A single dose of 10–100 μmol/kg PEITC in rats resulted in bioavailability ranging between 90–114%
*Dose↝, Furthermore, about 928.5±250nM peak plasma concentration of PEITC was achieved in human subjects, after the consumption of 100g watercress.
*Half-Life↝, time to reach peak plasma concentration was observed to be 2.6h±1.1h with a t1/2 4.9±1.1h
*toxicity↝, long term studies are required to establish the safety profile of PEITC, since regular intake of PEITC can cause its accumulation resulting in cumulative effects, which could be toxic.
GSH↓, The conjugation of PEITC with intracellular glutathione and the subsequent removal of the conjugate result in depletion of glutathione and alteration in redox homeostasis leading to oxidative stress
ROS↑, PEITC-mediated generation of reactive oxygen species (ROS) is known to be a general mechanism of action leading to cytotoxic effects, especially specific to cancer cells
CYP1A1↑, PEITC on one hand causes induction of CYP1A1 and CYP1A2; however, it inhibits activity of certain CytP450 enzymes, such as CYP2E1, CYP3A4 and CYP2A3
CYP1A2↑,
P450↓,
CYP2E1↑,
CYP3A4↓,
CYP2A3/CYP2A6↓,
*ROS↓, PEITC treatment caused a significant increase in the activities of ROS detoxifying enzymes such as glutathione peroxidase1, superoxide dismutase 1 and 2. This was also confirmed in human study where subjects were administered watercress, a major sour
*GPx1↑,
*SOD1↑,
*SOD2↑,
Akt↓, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types
EGFR↓, PEITC is also known to inhibit EGFR and HER2, which are important growth factors and regulators of Akt in different cancer models
HER2/EBBR2↓,
P53↑, PEITC-mediated activation of another tumor suppressor, p53 was observed in oral squamous cell carcinoma, causing G0/G1 phase arrest in multiple myeloma,
Telomerase↓, PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells
selectivity↑, generation of reactive oxygen species (ROS), which also has been shown to be the basis of selectivity of PEITC toward cancer cells leaving normal cells undamaged [
MMP↓, ROS generation by PEITC leads to mitochondrial deregulation and modulation of proteins like Bcl2, BID, BIM and BAX, causing the release of cytochrome c into cytosol leading to apoptosis
Cyt‑c↑,
Apoptosis↑,
DR4↑, induction of death receptors and Fas-mediated apoptosis
Fas↑,
XIAP↓, PEITC-mediated suppression of anti-apoptotic proteins like XIAP and survivin, which are up-regulated in cancer cells
survivin↓,
TumAuto↑, PEITC induces autophagic cell death in cancer cells
Hif1a↓, PEITC directly or indirectly suppresses HIF1α
angioG↓, is possible that PEITC can block angiogenesis by non-hypoxic mechanisms also.
MMPs↓, Various studies with PEITC have shown suppression of invasion through inhibition of matrix metalloproteinases along with anti-metastatic effects caused by suppression of ERK kinase activity and transcriptional activity of NFkB
ERK↓,
NF-kB↓,
EMT↓, PEITC was also known to inhibit processes, such as epithelial to mesenchymal transition (EMT), cell invasion and migration, which are essential pre-requisites for metastasis
TumCI↓,
TumCMig↓,
Glycolysis↓, reduced rates of glycolysis in PEITC-treated cells and depletion of ATP lead to death in prostate cancer cells
ATP↓,
selectivity↑, PEITC (5μM) treatment suppressed glycolysis in the cancer cells, but no changes were observed in normal cells.
*antiOx↑, the antioxidant effect is achieved at very low ITC levels in normal cells as shown in various animal models
Dose↝, At higher concentrations, ITCs may generate ROS by depleting antioxidant levels. PEITC is known to cause ROS generation, which is the major mechanism of toxicity in cancer cells
other↝, There is a continuous leakage of electrons from the electron transport chain (ETC), which is major source of ROS production. PEITC causes generation of endogenous ROS by disrupting mitochondrial respiratory chain
OCR↓, PEITC also inhibits mitochondrial complex III activity and reduces the oxygen consumption rate in prostate cancer cells
GSH↓, PEITC binds to GSH and causes its depletion in cancer cells leading to ROS-induced cell damage
ITGB1↓, PEITC was found to inhibit major integrins, such as ITGB1, ITGA2 and ITGA6 in prostate cancer cells
ITGB6↓,
ChemoSen↑, Using pre-clinical studies, improved outcomes were observed when the conventional agents, such as docetaxel, metformin, vinblastine, doxorubicin and HDAC inhibitors were combined with PEITC
*SIRT1↑, Piperlongumine (PL) activates the deacetylase ability of Sirt1 in vitro.
*cognitive↑, PL improves cognitive deficits in APP/PS1 mice.
*Aβ↓, PL reduces amyloid deposition and neuro-inflammation in the brain of APP/PS1 mice.
*Inflam↓,
*neuroP↑,
memory↑, Sirt1 has been shown to modulate synaptic plasticity and memory formation
Dose↓, PL induced Sirt1 deacetylase activity at a relatively low concentration, i.e. 1.5 uM, compared to the resveratrol
treatment.
NAD↑, PL
treatment at doses of 0.5 and 4 μM significantly increased the level of
NAD +
. These results indicate that PL might activate Sirt1, subsequently
changing the NAD +
/NADH ratio
*AMPK↑, Efficacy correlated with increased AMP-activated protein kinase (AMPK) activation and the senescence marker p21.
*P21↑,
*Dose↓, Our results show that low dietary exposures not only elicit biological changes in mouse and human tissues relevant to colorectal cancer chemoprevention, but they have superior efficacy compared to high doses
*chemoPv↑, Superior cancer chemopreventive efficacy of low dose resveratrol
Risk↓, Selenium deficiency is an established risk factor for colorectal cancer. It is believed that selenium supplementation and eating fish or foods rich in selenium and folic acid are factors modifying the incidence and development of colorectal cancer.
selm↑, Colorectal cancer patients had significantly lower serum selenium concentration than the comparison patients (67.24±15.55 μg/L vs 78.81±12.93 μg/L; P<0.001), and selenium concentration was below the reference range in a high percentage of colorectal
Dose↓, Mean selenium concentration differed significantly between both groups; 67.24±15.55 μg/L in the study group vs 78.81±12.93 μg/L in the comparison group (Figure 1; P<0.001). Selenium concentrations in the CRC patients were seldom within the reference
antiOx↑, Selenium has a strong antioxidant effect, although its excess causes toxic effects.
Dose↑, Therefore, selenium supplementation can be justified in people whose microelement concentration is in the lowest tertile (≤105.2 ng/mL)
Dose↝, arod et al showed that selenium supplementation in the Polish population should be considered in people with serum selenium concentration below 70 μg/L, with the aim of maintaining the concentration in the range of 70–90 μg/L
Dose↓, low Se intake is associated with increased risk of various cancers, the results of supplementation trials have been confusing
other↝, Se supply modulates protein synthesis, unfolded protein response,
Wnt, Nrf2 and inflammatory pathways
Dose↑, a food-based recommendation is desirable and Brazil nuts have been shown to improve Se status
eff↓, undoubtedly Se is a micronutrient of concern in plant-based diets in Se-poor areas
Dose↓, A dramatic decrease in the Se status in the UK had been observed over the 1980s in longitudinal studies on same subjects
*selenoP↑, Selenium is an essential trace element involved in many biological processes that are mediated through, at least, 25 selenoproteins expressed in humans.
*Dose↓, 50-200 μg/day have been used mainly for primary prevention (15), and Se supplementation at these doses for Se-deplete individuals has been associated with lower overall mortality and incidence of certain cancer types
Risk↓,
*toxicity↝, Animal laboratory studies have shown that the organic forms of Se are both more effective and safer than the commonly-used inorganic forms such as sodium selenite (SS), which are more genotoxic
Dose↑, All patients given 4,800 μg SLM twice daily achieved plasma Se levels >15 μM, the Se concentration required for reduced chemotherapy-induced toxicity and enhanced antitumor efficacy of chemotherapeutic drugs in preclinical animal models
chemoP↑, hence the optimal form and dose of Se to be used with chemotherapy or radiotherapy remains unclear.
radioP↑,
*memory↑, reduced thiamine can drive AD-like abnormalities, including memory deficits, plaques, and hyperphosphorylation of tau.
*p‑tau↓, Thiamine deficiency also increase the phosphorylation of tau
*cognitive↑, Thiamine deficiency has been linked to impaired cognition for decades
*Dose↝, For adults, excretion of less than 100 mcg/day thiamine in urine suggests insufficient thiamine intake, and less than 40 mcg/day indicates an extremely low intake.
*Dose↓, thiamine in plasma is reduced by about one-third in AD patients.
*Aβ↓, Thiamine deficiency greatly exacerbates plaque formation in mice genetically engineered to make plaques
*other↝, Furthermore, increasing thiamine with the compound benfotiamine reduces plaques, hyperphosphorylated tau, and memory deficits in a mouse genetically engineered to make plaques.
*eff↑, On the other hand, other compounds, such as solbutaimine, benfotiamine, and fursultiamine, have been designed to increase thiamine 5 to 10 times higher than thiamine and maintain these high levels for hours
*eff↑, benfotiamine was much more effective than fursultiamine in raising blood thiamine
| - |
Study, |
AD, |
NA |
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|
|
- |
Study, |
Park, |
NA |
|
|
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*Risk↑, As such, decreased dietary pantothenic acid intake may be associated with both PD incidence and severity.
*Dose↝, Due to the ease of obtaining sufficient amounts of pantothenic acid from food sources (5 mg daily for adults [19]), deficiency is rare, and usually only present in individuals with severe general malnutrition.
*Dose↓, Despite the rarity of pantothenic acid deficiency, significantly lower levels of dietary pantothenic acid intake have been observed in individuals with PD in comparison to healthy individuals
*other↝, despite a lack of outright pantothenic acid deficiency, supplementation may be a potential therapeutic option for the treatment of these neurodegenerative diseases.
*antiOx↑, major lipid-soluble antioxidant, which functions to maintain neurological integrity
*neuroP↑,
*Dose↓, Alarmingly, 90% of the population does not consume the RDA of 15 mg/day but average closer to half that value—around 7 mg/day [17]
*cognitive↑, individuals who consumed higher vitamin E-containing foods exhibited reduced cognitive decline per an adaptation of the Mini Mental State Examination (MMSE)
*other↝, benefit of vitamin E is skewed towards a pre-emptive measure to attenuate cognitive decline.
Showing Research Papers: 1 to 29 of 29
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 29
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 2, CYP1A1↑, 1, CYP2E1↑, 1, GSH↓, 2, ROS↓, 1, ROS↑, 7,
Metal & Cofactor Biology ⓘ
selm↑, 1,
Mitochondria & Bioenergetics ⓘ
ATP↓, 2, ETC↝, 1, MEK↓, 1, MMP↓, 3, mtDam↑, 1, OCR↓, 1, Raf↓, 1, SDH↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 1, citrate↓, 1, CPT1A↓, 1, CYP3A4↓, 1, FASN↑, 1, Glycolysis↓, 3, HK2↓, 1, NAD↑, 1, PDH↓, 1, PFK2?, 1, PKM2↓, 1, p‑S6K↓, 1, TCA↓, 1, β-oxidation↓, 1,
Cell Death ⓘ
Akt↓, 3, Apoptosis↓, 1, Apoptosis↑, 3, BAX↑, 1, Bax:Bcl2↑, 1, Bcl-2↓, 3, Casp2↑, 1, Casp3↑, 3, cl‑Casp3↑, 1, Casp8↑, 1, Casp9↑, 4, Cyt‑c↑, 2, DR4↑, 1, Fas↑, 2, Mcl-1↓, 1, MOMP↑, 1, p27↑, 1, survivin↓, 1, Telomerase↓, 2, TumCD↑, 2,
Kinase & Signal Transduction ⓘ
HER2/EBBR2↓, 1,
Transcription & Epigenetics ⓘ
other↝, 6, tumCV↓, 2,
Protein Folding & ER Stress ⓘ
ER Stress↑, 1, UPR↑, 1,
Autophagy & Lysosomes ⓘ
TumAuto↑, 2,
DNA Damage & Repair ⓘ
DNAdam↑, 5, P53↑, 1, cl‑PARP↑, 2, γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 1, CDK4↓, 1, cycD1/CCND1↓, 1, cycE/CCNE↓, 1, TumCCA↑, 1,
Proliferation, Differentiation & Cell State ⓘ
CD133↓, 2, CD44↓, 1, CSCs↓, 2, Diff↓, 1, EMT↓, 3, ERK↓, 2, IGF-1R↓, 1, p‑mTORC1↓, 1, n-MYC↓, 1, Nestin↓, 1, NOTCH↓, 1, PI3K↓, 1, PTEN↑, 2, SOX2↓, 1, STAT3↓, 1, TumCG↓, 2,
Migration ⓘ
Ca+2↓, 1, Ca+2↑, 1, ITGB1↓, 1, ITGB6↓, 1, MMP2↓, 1, MMP9↓, 1, MMPs↓, 1, TRPC1↑, 1, TSP-1↑, 1, TumCI↓, 2, TumCMig↓, 2, TumCP↓, 2, TumMeta↓, 1, uPA↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 3, EGFR↓, 2, EPR↑, 1, Hif1a↓, 3, VEGF↓, 1, VEGFR2↓, 1,
Barriers & Transport ⓘ
GLUT1↓, 1,
Immune & Inflammatory Signaling ⓘ
CCR7↓, 1, COX2↓, 1, CXCR4↓, 1, HMGB1↓, 1, IL12↓, 1, IL1β↓, 1, IL6↓, 1, Imm↑, 1, Inflam↓, 2, JAK2↓, 1, MCP1↓, 1, NF-kB↓, 1, PGE2↓, 2, T-Cell↝, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↝, 2, ChemoSen↑, 5, CYP1A2↑, 1, CYP2A3/CYP2A6↓, 1, Dose?, 1, Dose↓, 22, Dose↑, 6, Dose↝, 6, Dose∅, 1, eff↓, 4, eff↑, 14, eff↝, 2, P450↓, 2, RadioS↑, 2, selectivity↑, 10,
Clinical Biomarkers ⓘ
EGFR↓, 2, HER2/EBBR2↓, 1, IL6↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 1, chemoP↑, 1, memory↑, 1, OS↑, 2, radioP↑, 1, Remission↑, 2, Risk↓, 5, toxicity↓, 2,
Total Targets: 143
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 4, GPx1↑, 1, GSH↑, 1, HO-1↑, 1, NRF2↑, 1, ROS↓, 2, selenoP↑, 1, SOD1↑, 1, SOD2↑, 1, Trx1↑, 1, TrxR1↑, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 1, NADPH↑, 1, SIRT1↑, 2,
Transcription & Epigenetics ⓘ
other↝, 4,
Cell Cycle & Senescence ⓘ
P21↑, 1,
Angiogenesis & Vasculature ⓘ
Hif1a↑, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
Inflam↓, 1,
Cellular Microenvironment ⓘ
Temp↝, 1,
Synaptic & Neurotransmission ⓘ
p‑tau↓, 1,
Protein Aggregation ⓘ
Aβ↓, 2,
Drug Metabolism & Resistance ⓘ
BioAv↑, 2, Dose↓, 8, Dose↝, 4, eff↑, 4, Half-Life↝, 1,
Clinical Biomarkers ⓘ
BP↓, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiTum↑, 1, chemoPv↑, 1, cognitive↑, 3, memory↑, 1, MusCon↓, 1, neuroP↑, 3, Risk↑, 1, toxicity↝, 2,
Total Targets: 37
Scientific Paper Hit Count for: Dose, Dosage
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#:1114 State#:% Dir#:1
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