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⟱
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in-vitro, |
PC, |
Bxpc-3 |
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in-vitro, |
PC, |
PANC1 |
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in-vitro, |
PC, |
MIA PaCa-2 |
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in-vivo, |
NA, |
NA |
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mtDam↑, in cancer cells only. ALA protected normal cells
ROS↑, in cancer cells only. ALA protected normal cells
*toxicity↓, Nonmalignant CRL-4023 and LX-2 cells were treated with α-lipoic acid at concentrations of 0.5 mM, 1 mM, 2 mM and 3 mM, Both cell lines were largely resistant to any concentration
Dose∅, ALA dose: we used α-lipoic acid concentrations of 0.5 and 1 mM
selectivity↑, higher sensitivity of malignant cells to AgNPs.
*BioAv↝, For enteric tablets, ABB varied from 36–104%
*eff↓, but it was reduced to 22–57% when consumed with a high-protein meal, due to slower gastric emptying.
*BioAv↝, garlic powder capsules gave 26–109%
*BioAv↝, Kwai garlic powder tablets, which have been used in a large number of clinical trials, gave 80% ABB, validating it as representing raw garlic in those trials
*eff↑, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*Half-Life∅, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*eff↑, all brands of normal tablets gave high allicin bioavailability
*eff↑, Hence, both low-protein and high-protein meals would provide a gastric pH ≥ 4.0 for an ample amount of time for the alliinase in disintegrated normal tablets and capsules to convert most of the alliin to allicin in the stomach.
*Dose∅, Three tablets has been the most common dose used in these trials. The N1 tablets in these trials have been consistently standardized to contain 3.9 mg alliin/tablet and to yield 1.8 mg allicin/tablet
*eff↑, The bioavailability of allicin from garlic powder supplements containing alliin and active alliinase can be as high as that from an equivalent amount of crushed raw garlic containing maximum allicin, when consumed with a meal.
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vitro+vivo, |
Lung, |
A549 |
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vitro+vivo, |
Lung, |
PC9 |
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Apoptosis↑,
ROS↑, mitochondrial ROS(remarkably increased)
PDK1↓,
NRF2↓,
PDK1↓,
Bcl-2↓,
Casp9↑,
Dose∅, 1.5 mM LA for 24 h
*BioAv↓, We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range cu
Half-Life∅, elimination half-life (T1/2) averaging 2.52 ± 0.56h
*BioAv↓, bioavailability is in the region of 30%
Dose∅, Blood and urine samples were taken following a meal consisting of 2g parsley/kg body weight–which was equivalent to ∼17mg of apigenin -> 28–337nmol/L at 6–10h after consumption
eff↑, Apigenin and quercetin enhance their own and each other’s bioavailability by downregulating the activity of ABC transporters
CYP1A2↓, status of apigenin as an inhibitor of CYP1A2, CYP2C9 and CYP3A4
CYP2C9↓,
CYP3A4↓,
*BioAv↑, apigenin was developed as SNEDDS to solve its dissolution problem and enhance oral bioavailability
*Dose∅, Smix ratio of 1:1 and concentrations of Gelucire 44/14, Tween 80, and PEG 400 in the ranges of 5–40% w/w, 30–47.5% w/w, and 30–47.5% w/w, respectively, as shown in Table 1.
Dose∅, oral administration of apigenin (20 and 50 μg/mice) for 20 weeks reduced tumor volumes
TumVol↓,
Dose∅, 15-week period of oral administration of apigenin (2.5 mg/kg) in hamsters resulted in reduction of tumor volume
COX2↓, topical application of apigenin (5 μM) prior to UVB-exposure attenuated the expression of COX-2 and hypoxia inducible factor (HIF)-1α,
Hif1a↓,
TumCCA↑, apigenin was capable to promote cell cycle arrest and induction of apoptosis through p53-related pathways
P53↑,
P21↑, induction of the cell cycle inhibitor p21/WAF1,
Casp3↑,
DNAdam↑, DNA fragmentation
TumAuto↝, Only a small number of studies have observed the induction of autophagy in response to apigenin and the results are controversial
*BioAv↓, Apigenin is not easily absorbed orally because of its low water solubility, which is only 2.16 g/mL
*Half-Life∅, Apigenin is slowly absorbed and eliminated from the body, as evidenced by its half‐life of 91.8 h in the blood
selectivity↑, selective anticancer effects and effective cell cytotoxic activity while exhibiting negligible toxicity to ordinary cells
*toxicity↓, intentional consumption in higher doses, as the toxicity hazard is low
Wnt/(β-catenin)↓, inhibiting the Wnt/β‐catenin
P53↑,
P21↑,
PI3K↓,
Akt↓,
mTOR↓,
TumCCA↑, G2/M
TumCI↓,
TumCMig↓,
STAT3↓, apigenin can activate p53, which improves catalase and inhibits STAT3,
PKM2↓,
EMT↓, reversing increases in epithelial–mesenchymal transition (EMT)
cl‑PARP↑, apigenin increases the cleavage of poly‐(ADP‐ribose) polymerase (PARP) and rapidly enhances caspase‐3 activity,
Casp3↑,
Bax:Bcl2↑,
VEGF↓, apigenin suppresses VEGF transcription
Hif1a↓, decrease in hypoxia‐inducible factor 1‐alpha (HIF‐1α
Dose∅, effectiveness of apigenin (200 and 300 mg/kg) in treating CC was evaluated by establishing xenografts on Balb/c nude mice.
GLUT1↓, Apigenin has been found to inhibit GLUT1 activity and glucose uptake in human pancreatic cancer cells
GlucoseCon↓,
angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,
*SREBF2↓, apigenin prevented SREBP-2 translocation and reduced the downstream gene HMGCR transcription
*HMGCR↓,
*Dose∅, oral dosages of 5.4 mg apigenin/kg body weight would produce a C max value of 16.5 μm in serum
*BioAv?, Given its high bioavailability, its action on cholesterol synthesis could be achievable in this administrative method
TNF-α↓,
IL1β↓,
IL6↓,
IL10↓,
COX2↓, blocks the nitric oxide-mediated cyclooxygenase-2 expression
iNOS↓,
Inflam↓,
Dose∅, apigenin contents were reported high in celery and parsley with amounts of 19 and 215 mg per 100 g, respectively
Dose∅, dried parsley contains highest concentration of apigenin (45,035 μg/g). The dried chamomile flowers contain 3,000 to 5,000 μg/g of apigenin.
OS↑, Among the flavonoid-treated patients with resected colon cancer (n = 14), there was no cancer recurrence and one adenoma developed
Remission↓,
Dose∅, The flavonoid- treated patients took a daily dose of 2 tablets of the flavonoid mixture[24] containing 10 mg apigenin and 10 mg epigallocatechin-gallate per tablet.
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in-vitro, |
Nor, |
HDFa |
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in-vitro, |
PC, |
AsPC-1 |
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in-vitro, |
PC, |
MIA PaCa-2 |
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in-vitro, |
Pca, |
DU145 |
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in-vitro, |
Pca, |
LNCaP |
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in-vivo, |
NA, |
NA |
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selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly
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in-vitro, |
Ovarian, |
SKOV3 |
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in-vitro, |
Ovarian, |
TOV-21G |
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TumCG↓,
TumCCA↑, G2/M phase
ROS↑, Baicalein-induced G2/M phase arrest is associated with an increased reactive
oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation
DNAdam↑,
Chk2↑,
Dose∅, produced significant ROS in a dose- and time-dependent manner in SKOV-3 cells
p‑γH2AX↑, baicalein treatment increased the phosphorylation of H2AX (γH2AX)
CDC25↓,
CHK1↓,
cycD1/CCND1↓,
eff↓, CHK2 inhibitor indeed reduced the extent of CHK2 phosphorylation (Figure 4A) and protected SKOV-3 cells from baicalein-mediated G2/M arrest (Fig
12LOX↓, the pro-oxidative effect of baicalein, a specific inhibitor of 12-LOX, on ovarian cancer cells may occur through inhibiting the activity of 12-LOX, thereby inducing the accumulation of hydroxyl radicals.
Apoptosis↑,
Dose∅, Baicalein at 40 μM significantly hindered human oral cancer KB cells
ROS↑, anticancer effect of baicalein is likely due to its potential to improve ROS level and hence the increased apoptotic activity.
Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate
combination at high temperatures. However, a low amount of CA is
yielded via this pathway
eff↝, Decyl CA (DCA) is a
novel derivative of CA but its role in affecting colorectal cancer has not
been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both
autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM)
can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax
upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 μM) and
metformin (10 mM) is of interest in cervical squamous cell carcinoma
therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.
Dose∅, Black chokeberries seem to be the most potent source of caffeic acid (645 mg/100 g of dry weight)
ROS⇅, Therefore, we will mention the antioxidant (and prooxidant) effects of caffeic acid only briefly
NF-kB↓, In HepG2 cells, caffeic acid (100 µM) inhibited the activity of NF-κB/IL-6/STAT3 signaling, which decreased the expression of VEGF
STAT3↓,
VEGF↓,
MMP9↓, inhibited another downstream product of NF-κB: matrix metalloproteinase 9 (MM-9), which promotes tumor invasiveness and metastases
HSP70/HSPA5↑, caffeic acid (20 μM) also decreased the expression of mortalin(mitochondrial 70 kDa heat shock protein),
AST↝, normalized levels of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol, HDL and LD
ALAT↝,
ALP↝,
Hif1a↓,
IL6↓,
IGF-1R↓,
P21↑,
iNOS↓,
ERK↓,
Snail↓,
BID↑,
BAX↑,
Casp3↑,
Casp7↑,
Casp9↑,
cycD1/CCND1↓,
Vim↓,
β-catenin/ZEB1↓,
COX2↓,
ROS↑, the chelating ability of caffeic acid is also responsible for its occasional pro-oxidant ability. After chelating Cu2+, the Cu2+ can be reduced to Cu+. combination of caffeic acid and endogenous copper ions can result in oxidative damage
ROS↑, CA can become a pro-oxidant due to its ability to chelate metals such as copper (Cu)
antiOx↑, CA, including its antioxidant, anti-inflammatory, and anticancer properties.
Inflam↓,
AntiCan↑,
NF-kB↓, ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK1/2
STAT3↓,
ERK↓,
ChemoSen↑, mitigation of chemotherapy and radiotherapy-induced toxicity
RadioS↑,
AMPK↑, CA (100 μM) alone or in combination with metformin (10 mM) is efficient in stimulating the AMPK signaling pathway, which acts by preventing de novo synthesis of unsaturated fatty acids, consequently reducing cancer cell survival
eff↑, combined treatment with cisplatin (5 µM) and CA (10 µM) restored the chemo-sensitizing effect against cisplatin-resistant ovarian endometrioid adenocarcinoma cells (A2780)
selectivity↑, dual capacity of CA to act as an antioxidant during carcinogenesis and as a pro-oxidant against cancer cells, promoting their apoptosis or sensitizing them to chemotherapeutic drugs
COX2↓, CA has been discovered to impede Cyclooxygenase-2 (COX-2), an enzyme pivotal in the inflammatory cascade.
Dose∅, 50 to 10 µM, effectively suppresses COX-2
PHDs↓, CA serves as a potent inhibitor of prolyl hydroxylase-2 (PHD2),
MMP9↓, CA has been identified as an inhibitor of MMP-9
MMP2↓, CA and CAPE at doses of 5 mg/kg subcutaneously or 20 mg/kg orally. Both compounds exhibited the inhibition of MMP-2 and -9,
Dose∅, CA (0–200 μM) induces apoptosis and cell cycle arrest by increasing the expression profile of caspase 1 and caspase 3
Dose∅, CA (200–800 μM) has been shown to promote Ca2+ accumulation
Ca+2↑,
Dose?, Treatment with CA at a concentration of 20 μM disrupts mitochondrial function, which leads to several effects: increased Caspase-9 activity, elevated levels of ROS, and a decrease in membrane potential (Δψm)
MMP↓,
RadioS↑, Studies conducted on cells and animals indicate that CA enhances the efficacy of chemotherapy and radiotherapy, potentially mitigating their adverse effects and improving patient outcomes with minimal side effects
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in-vitro, |
Bladder, |
TSGH8301 |
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in-vitro, |
CRC, |
T24/HTB-9 |
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ENOX2↓, capsaicin downregulates tNOX expression
TumCCA↑, Capsaicin Downregulates tNOX and Induces Cell Cycle Arrest at G1 Phase
ERK↓, inhibit the activation of ERK
p‑FAK↓,
p‑pax↓,
TumCMig↓,
EMT↓,
SIRT1↓, downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells
Dose∅, 100 and 200 μM effectively reduced tNOX expression in bladder cancer TSGH8301 and T24
ROS↑, capsaicin dose-dependently increased ROS generation
MMP↓,
Bcl-2↓,
Bak↑,
cl‑PARP↑,
Casp3↑,
SIRT1↓, 100 and 200 μM capsaicin decreased SIRT1 expression
ac‑P53↑, concurrently increased p53 acetylation
BIM↑, enhanced the expression level of Bim
p‑RB1↓, downregulation of phosphorylated Rb and cyclin D,
cycD1/CCND1↓,
Dose∅, Interestingly, cell migration was somewhat increased with 10 μM accompanied by up-regulation of tNOX expression
β-catenin/ZEB1↓,
N-cadherin↓,
E-cadherin↑,
AntiCan↑, Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers.
TumCG↓,
angioG↓,
TumMeta↓,
BioAv↓, clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties
BioAv↓, capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting
BioAv↑, All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems.
selectivity↑, Most importantly, these long-acting capsaicin formulations selectively kill cancer cells and have minimal growth-suppressive activity on normal cells.
EPR↑, The EPR effect is a mechanism by which high–molecular drug delivery systems (typically prodrugs, liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues
eff↓, The efficiency of such extravasation is maximum when the size of the liposomes less than 200 nm The CAP-CUR-GLY-GAL-LIPO were spherical in shape with a narrow range of size distribution ranging from 135–155nm
ChemoSen↑, The chemosensitization and anti-tumor activity of capsaicin involves multiple molecular pathways
Dose∅, oral, Intravenous (IV), and Intraperitoneal (IP) options
Half-Life∅, oral metabolized in 105mins, T1/2in blood=25mins.
eff↑, presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin
Warburg↓, hypothesis that extracellular citrate might play a major role in cancer metabolism and is responsible for a switch between Warburg effect and OXPHOS
OXPHOS↓,
Dose∅, 10 mM citrate, cancer cells were shown to have decreased proliferation, ATP synthesis,
TumCP↓,
ATP↓,
eff↑, increased apoptosis and sensitivity to cis-platin
Apoptosis↑,
TumCG↓, high doses of citrate in vivo decreased tumour growth
PFK1↓, increased levels of cytosolic citrate taken up from the extracellular space would decrease phosphofructokinase-1 (PFK-1) activity
Dose∅, 10 grams with each meal, every eight hours, and omeprazole 40 mg every 12 hours
Weight↑,
OS↑,
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Case Report, |
Thyroid, |
NA |
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OS↑,
Weight↑, increasing health
Dose∅, 1-1.5g for 20kg boy
eff↑, when his treatment formally began; he also received omeprazol, 20 mg and sucralfate, 500 mg a day.
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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in-vitro, |
Lung, |
A549 |
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in-vitro, |
Melanoma, |
WM983B |
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in-vivo, |
NA, |
NA |
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|
TumCG↓,
eff↑, additional benefit accrued in combination with cisplatin
T-Cell↑, significantly higher infiltrating T-cells
p‑IGF-1R↓, citrate inhibited IGF-1R phosphorylation
p‑Akt↓, inhibited AKT phosphorylation
PTEN↑, activated PTEN
p‑eIF2α↑, increased expression of p-eIF2a
p-eIF2a was decreased when PTEN was depleted
OCR↓, citrate treatment of A549 cells dramatically reduced oxygen consumption
ROS↓, observed a decrease in ROS in A549
ECAR∅, acidification rate (ECAR) and found it to be unchanged
IL1↑, s (e.g. interleukin-1, tumor necrosis factor-alpha, etc) and anti-inflammatory cytokines (e.g. interleukin-10 and interleukin 1 receptor antagonist) are activated
TNF-α↑,
IL10↑,
IGF-1R↓, Citrate Inhibits IGF-1R Activation And Its Downstream Pathway
eIF2α↑, eIF2α activity was increased in A549 cells after citrate treatment
PTEN↑, PTEN was activated
TCA↓,
Glycolysis↓, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
selectivity↑, citrate may inhibit tumor growth via inhibiting glycolysis and the TCA cycle and that this effect appears to be selective to tumor tissue.
*toxicity∅, Chronic citrate treatment was non-toxic as evidenced by gross pathology in numerous organs (liver, lung, spleen and kidney)
Dose∅, corresponding to approximately 56 g of citrate in a 70 kg person
Dose∅, 2.5 μg.ml-1 LD50 value for CuI
Dose∅, LD50 value 10 μg.ml-1 for the corresponding Cu(PO4)2 Nps
ROS↑, Both types of NPs cause apoptotic mediated cell death by inducing ROS-mediated DNA damage
eff↓, copper serves as a limiting factor for multiple aspects of tumor progression, including growth, angiogenesis and metastasis, has prompted the development of copper-specific chelators as therapies to inhibit these processes.
eff↑, Another therapeutic approach utilizes specific ionophores that deliver copper to cells to increase intracellular copper levels.
Dose∅, therapeutic window between normal and cancerous cells when intracellular copper is forcibly increased, is the premise for the development of copper-ionophores endowed with anticancer properties.
eff↑, In comparison to platinum-based drugs, these promising copper coordination complexes may be more potent anticancer agents, with reduced toxicity toward normal cells and they may potentially circumvent the chemoresistance
angioG↑, These findings unquestionably place copper as a potent inducer of the angiogenic process.
ROS↑, Copper is a redox active metal that can enhance the production of ROS, which subsequently can damage most biomolecules
eff↑, combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay
Dose∅, IC50 value for Curcumin is calculated as 16.52 mM and for Ellagic acid the IC50 Value is
19.47 mM. The combination of Curcumin and Ellagic acid has IC50 value 10.9 mM.
ROS↑, Curcumin alone increases the ROS level significantly. Similarly the C + E treated cells exhibited a very high magnitude of ROS level.
DNAdam↑, Curcumin and Ellagic acid
show mild degree of DNA damage at this concentration but the
C + E treated cells shows greater degree of DNA damage
P53↑, C + E treated cells show greater degree of stabilization of p53
P21↑, Elevated expression of p21 in response to Curcumin and C + E
treatment
BAX↑, But the C + E treated cells showed higher expression of Bax
Dose∅, Curcumin daily shows detectable levels of Curcumin in plasma and urine and the concentration is close to 11.1 nMol/l
*MAOA↓, MAO activity was inhibited by curcumin and ellagic acid
*Dose∅, however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM)
Dose?, MAO-B by curcumin (IC50 500.46 nM) and ellagic acid (IC50 412.24 nM)
| - |
in-vitro, |
Cerv, |
HeLa |
|
|
|
- |
in-vitro, |
Laryn, |
FaDu |
|
|
|
selectivity↑, previously demonstrated that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxic effects of radiation on normal human fibroblasts
RadioS↑,
TrxR↓, inhibitory activity of curcumin on the anti-oxidant enzyme Thioredoxin Reductase-1 (TxnRd1) is required for curcumin-mediated radiosensitization of squamous carcinoma cells
ROS↑, induced reactive oxygen species
ERK↑, sustained ERK1/2 activation
Dose∅, Curcumin treatment resulted in a dose-dependent decrease in TxnRd activity with an IC50 of approximately 10 µM in both cell lines
cl‑PARP↑, curcumin induced a robust increase in cleaved PARP
| - |
Case Report, |
lymphoma, |
NA |
|
|
|
Remission↑, Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later.
p‑PDKs↓, DCA has been shown to block this phosphorylation by PDK at the mitochondrial membrane level and decrease glycolysis in favor of glucose oxidation
Glycolysis↓,
i-Ca+2↓, This return to a normal metabolism of glucose allows for major changes including a decrease in Ca++ intracellularly, and stabilization of the mitochondria allowing a reactivation of caspases in cancer cells leading to apoptosis
toxicity↓, A reversible, minimal nerve damage can be considerably reduced by a daily thiamine intake of several hundred milligrams for humans. thiamine amount varies from 50 mg/day to 100 mg/day depending on whether it is administered orally or injected
Dose∅, A Non-Hodgkin′s lymphoma patient taking 10 mg/kg [750 mg] of dichloroacetate daily of his own accord, had a complete remission of his Non-Hodgkin′s lymphoma cancer after four months
| - |
in-vitro, |
BC, |
MCF-7 |
|
|
|
- |
in-vitro, |
BC, |
T47D |
|
|
|
- |
in-vitro, |
Nor, |
MCF10 |
|
|
|
PDKs↓, Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism
eff↑, DCA and metformin are used in combination, synergistic induction of apoptosis of breast cancer cells occurs.
ROS↑, Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production.
PDK1↓,
lactateProd↓, also diminishes metformin promoted lactate production.
p‑PDH↑, DCA is an inhibitor of pyruvate dehydrogenase kinase (PDK) which phosphorylates pyruvate dehydrogenase (PDH), rendering it inactive
Dose∅, DCA (2.5 mM) and metformin (1 mM)
OCR↑, DCA treated cells had a significantly higher oxygen consumption rate compared to control cells.
DNA-PK↑,
γH2AX↑, phosphorylatoin of histone H2AX (p-H2AX), which is a useful surrogate marker of such DNA damage
cl‑PARP↑, large increase of cleaved PARP
selectivity↑, Importantly, we also show that this combination of drugs does not kill non-transformed breast epithelial cells MCF10A under the same conditions in which the drugs kill cancer cells.
*toxicity∅, does not kill non-transformed breast epithelial cells MCF10A under the same conditions in which the drugs kill cancer cells.
| - |
Case Report, |
Melanoma, |
NA |
|
|
|
OS↑, DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of recurrent metastatic melanoma for over 4 years’ duration, with trivial side effects.
toxicity↓, DCA was noted to have an absence of renal, pulmonary, bone marrow and cardiac toxicity
Dose∅, Active hexose correlated compound or AHCC , dandelion root, curcumin, and astragalus root. Parenteral therapy was also started, which consisted of intravenous vitamin C twice weekly and subcutaneous European mistletoe extract. +vegan diet
Dose∅, DCA 500 mg 3 times per day, which was equivalent to 17 mg/kg per day (manufacturer: Tokyo Chemical Industry, United States) in addition to maintaining the other natural therapies. 2 wk on and 1 wk off
Dose∅, To minimize the occurrence of DCA side effects, 3 additional natural medications were prescribed: Oral acetyl L-carnitine 500 mg 3 times a day, oral benfotiamine 80 mg twice a day and oral R-alpha lipoic acid 150 mg 3 times a day
QoL∅, DCA therapy can be used without reducing quality of life
| - |
in-vitro, |
GBM, |
U87MG |
|
|
|
- |
in-vitro, |
GBM, |
U251 |
|
|
|
PDKs↓, dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor.
eff↑, By combining DCA with PENAO, the two drugs worked synergistically to inhibit cell proliferation (but had no significant effect on non-cancerous cells)
selectivity↑,
MMP↓, induced oxidative stress and depolarized mitochondrial membrane potential, which in turn activated mitochondria-mediated apoptosis
ROS↑,
Apoptosis↑,
Warburg↓, Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor that reverses the Warburg effect
eff↑, DCA has been demonstrated to sensitize cancer cells towards apoptosis and enhance the effects of several anti-cancer agents, including arsenic trioxide [20], cisplatin [22,23] and metformin [24].
Dose∅, IC50 values of DCA were at suprapharmacological millimolar level
toxicity∅, whilst the IC50 values of DCA for non-cancerous cells were not reached (DCA concentration in this study was tested up to 50 mM)
BG↓, KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer.
TumCG↓,
OS↑,
eff↑, While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls.
Dose∅, Mice undergoing HBO2T received 100% O2 for 90 minutes at 1.5 ATM gauge (2.5 ATM absolute) three times per week (M, W, F) in a hyperbaric chamber (Model 1300B, Sechrist Industries, Anaheim, CA).
KeyT↑, only the KD+HBO2T animals showed significantly increased ketones compared to controls
eff↑, we hypothesized that combining these non-toxic treatments would provide a powerful, synergistic anti-cancer effect.
cachexia↓, While low carbohydrate or ketogenic diets promote weight loss in overweight individuals, they are also known to spare muscle wasting during conditions of energy restriction and starvation
ChemoSen↑, KD improves quality of life and enhances the efficacy of chemotherapy treatment in the clinic
*ROS↓, ketone body metabolism protects cells from oxidative damage by decreasing ROS production. cancer cells are unable to effectively metabolize ketone bodies; we do not expect that ketones would confer the same protective effects onto the cancer cells
ROS↑, HBO2T increases ROS production within the cell which can lead to membrane lipid peroxidation and cell death
lipid-P↑,
selectivity↑, KD weakens cancer cells by glucose restriction and the inherent anti-cancer effects of ketone bodies while simultaneously conferring a protective advantage to the healthy tissue capable of ketone metabolism.
toxicity∅, HBO2T should be considered a safe treatment for patients with varying malignancies and that there is no convincing evidence its use promotes cancer progression or recurrence
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage
Dose∅, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1, M2-2 and P1-1with IC50 values ranging from 0.04 to 5 μM
GSTs↓,
TumCP↓,
cycD1/CCND1↓,
Apoptosis↑,
PI3K↓, strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA
Akt↓,
ROS↑, production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA
Casp3↑, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells
Cyt‑c↑,
Bcl-2↓,
TumCCA↑, induces G2/M phase cell cycle arrest in HCT-15 cells
Dose∅, since 60 lM of the drug concentration could cause attentional loss of cells (60 and 45 % were viable in 12 and 24 h treatment, respectively) for crucial experiments, we used this dosage to assess the effect of EA in killing HCT-15 cells
ALP↓, significant decrease in the activity of ALP at 60 lM concentration of EA for the 12 h treatment
LDH↓, decrease in the activity of LDH in cells was proportional to increase in the incubation time with EA.
PCNA↓, EA down-regulated the expressions of PCNA and cyclin D1
P53↑, EA promoted p53 gene expression
Bax:Bcl2↑, increase in the Bcl-2/Bax ratio
| - |
in-vitro, |
Cerv, |
HeLa |
|
|
|
- |
in-vitro, |
Liver, |
HepG2 |
|
|
|
- |
in-vitro, |
BC, |
MCF-7 |
|
|
|
- |
in-vitro, |
Lung, |
A549 |
|
|
|
- |
in-vitro, |
Nor, |
HUVECs |
|
|
|
eff↑, Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW
Dose∅, EA inhibited HeLa cells with an IC50 of 35 μg/mL
*BioAv↑, EA is not sensitive to high temperatures and is not highly soluble in many solvents.
selectivity↑, selectivity index varied from 7.4 for Hela to about 1 for A549
TumCP↓, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
Casp↑, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
PTEN↑,
TSC1↑,
mTOR⇅,
Akt↓, AKT, PDK1 expression were down-regulated
PDK1↓,
E6↓, mRNA levels of E6/E7 were determined to decrease gradually with the increase in EA incubation time and concentration
E7↓,
DNAdam↑, When DNA damage is introduced into cells from exogenous or endogenous sources there is an increase in the amount of intracellular reactive oxygen species (ROS)
ROS↑,
*BioAv↓, EA cannot be exploited for in vivo therapeutic applications in the current situation because of its poor water solubility and accordingly low bioavailability.
*BioEnh↑, As Lei [52] reported that EA in pomegranate leaf is rapidly absorbed and distributed as well as eliminated in rats
*Half-Life∅, blood concentration peaked at 0.5 h with Cmax = 7.29 μg/mL, and the drug concentration decreased to half of the original after 57 min of administration
*Dose∅, A pharmacokinetic study in healthy individuals receiving single doses of EGCGrevealed that plasma concentrations exceeded 1 μM only with doses of >1 g
Half-Life∅, peak levels observed between 1.3 and 2.2 h (and a half-life (t1/2z) of 1.9 to 4.6 h)
BioAv∅, oral bioavailability of 20.3% relative to intravenous admistration
BBB↑, EGCG can cross the blood–brain barrier, allowing it to reach the brain
toxicity∅, Isbrucher et al. found no evidence of genotoxicity in rats following oral administration
of EGCG at doses of 500, 1000, or 2000 mg/kg, or intravenous injections of 10, 25, or
50 mg/kg/day.
eff↓, interaction with the folate transporter has been reported, leading to reduced
bioavailability of folic acid
Apoptosis↑,
Casp3↑,
Cyt‑c↑, cytochrome c release
cl‑PARP↑,
DNMTs↓,
Telomerase↓,
angioG↓,
Hif1a↓,
NF-kB↓,
MMPs↓,
BAX↑,
Bak↑,
Bcl-2↓,
Bcl-xL↓,
P53↑,
PTEN↑,
IGF-1↓,
H3↓,
HDAC1↓,
*LDH↓, reduces LDL cholesterol, decreases oxidative stress by neutralizing ROS
*ROS↓,
ROS↑, GA was found to increase ROS levels
Dose∅, (50–400 µM, from a time phase of 30 min to 24 h)
MMP↓, loss of mitochondrial membrane potential
GSH↑, antioxidant enzyme glutathione peroxidase (GSH) decreased when treatment was administered above 100 µM
| - |
in-vitro, |
HCC, |
SMMC-7721 cell |
|
|
|
AntiTum↑, Gambogic acid (GA), a natural product that has been used in traditional Chinese medicine for centuries, demonstrates potent anticancer activity in numerous types of human cancer cells and has entered phase II clinical trials
TrxR↓, GA may interact with TrxR1 to elicit oxidative stress
TrxR1↓,
ROS↑,
Apoptosis↑, eventually induce apoptosis in human hepatocellular carcinoma SMMC-7721 cells.
Dose∅, GA effectively inhibited TrxR1 with an IC 50 around 1.2 uM,
Dose?, Under our experimental conditions, GA with concentration less than 5 uM gives only marginal inhibition
of Trx
| - |
in-vitro, |
Pca, |
PC3 |
|
|
|
- |
in-vitro, |
Pca, |
LNCaP |
|
|
|
- |
in-vitro, |
Pca, |
DU145 |
|
|
|
ROS↑, GA disrupted cellular redox homeostasis, observed as elevated reactive oxygen species (ROS), leading to apoptotic and ferroptotic death.
Apoptosis↑,
Ferroptosis↑,
Trx↓, GA inhibited thioredoxin
eff↑, Auranofin (AUR), a thioredoxin reductase (TrxR) inhibitor was the one compound that demonstrated additive growth inhibition together with GA when both were combined at sub-thresh hold concentrations
TrxR↓, GA may inhibit the thioredoxin (Trx) system, which mainly composes NADPH, TrxR, and Trx.
Dose∅, GA demonstrated sub-micromolar activity (IC50 = 185nM) which was 50 times more potent than the next most active compounds, curcumin and tanshinone (CT)
MMP↓, GA treatment showed increasing loss of membrane polarity at 4 and 6 hours in PCAP-1 cells
eff↑, GA enhanced the cell killing observed for either docetaxel (DOX) or enzalutamide (ENZA)
Casp↑, These results suggest that GA initiates CASP-dependent death of PCAP-1 cells and that both iron-dependent oxidative injury and direct CASP activation contribute
NADPH↓, These results suggest that GA may inhibit the thioredoxin (Trx) system, which mainly composes NADPH, TrxR, and Trx.
TrxR↓,
ChemoSen↑, potential use of GA in combination with standard chemotherapeutic (docetaxel) and anti-androgen endocrine (enzalutamide) therapies for advanced PrCa.
AR↓, inhibit PrCa growth, in part by inhibiting AR signaling
| - |
Case Report, |
Obesity, |
NA |
|
|
|
*Dose∅, two 80 mg capsules of “Garcinia Cambogia 5:1 Extract” three times daily before meals for five months
*other↑, drug-induced liver injury
AntiAg↝, Taking ginger four gram once daily did not show an effect on the platelet aggregation using Adenosine Diphosphonate, Arachidonic Acid, Collagen and Ristocetin, except Epinephrine where reduction in platelet aggregation had been observed
Dose∅, Dose increment to ginger 4 g twice daily does not influence the platelet aggregation using any of the agonists.
*ACLY↓, HCA is a competitive inhibitor of ATP citrate lyase
*toxicity∅, No remarkable toxicity results were detected, demonstrating the safety of HCA-SX.
*Dose∅, 4666.7 mg HCA-SX (providing 2,800 mg HCA) in three equally divided doses 30-60 min before meals,
Dose∅, HCAs such as caffeic, ferulic, and coumaric acids in fruits can be as high as 2 g/kg fresh weight [13], with caffeic acid (free or esterified) accounting for the overwhelming majority (75%–100%).
ROS⇅, Consumption of foods rich in caffeic acid has also been shown to protect against carcinogenesis due to its antioxidant and pro-oxidant properties.
Dose∅, Coffee beans are an important source of HCAs such as caffeic and chlorogenic acids; a single cup of coffee contains between 70 and 350 mg of these compounds
| - |
in-vitro, |
Lung, |
A549 |
|
|
|
- |
in-vivo, |
Lung, |
NA |
|
|
|
AntiCan↑, administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice
Igs↓, administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice by a decline in IgG and IgM level
lipid-P↓,
ROS↑, elevation of ROS production and caspase activity (caspase-3 and caspase-9)
Casp3↑,
Casp9↑,
ChemoSideEff↓, effective chemo preventative agent against lung carcinogenesis.
Dose∅, The IC50 value of sinapic acid was 50 µM. Hence, 50 and 75 µM dosage was selected for the additional assessments of anti-cancer efficacy of sinapic acid in the A459 cells
*BioAv↓, Studies have shown that SA is poorly soluble in water, but soluble in carbitol and freely soluble in DMSO
*toxicity↓, SA is found to be generally non-toxic
Dose∅, oral administration of SA up to 80 mg/kg body weight reduced the number of aberrant crypt foci up to 34.55%
ROS⇅, Other than its potent antioxidant function, SA also possesses pro-oxidant effect that has been identified to affect the redox state of tumor cells
ROS↑, SA at higher concentrations acts as a potent pro-oxidant agent, resulting in increased generation of free radicals. (50 and 75 μM) increased ROS accumulation
Igs↑, SA administration markedly improved the levels of IgG and IgA in
TumCCA↑, SA induced G2/M phase cell cycle arrest
TumAuto↑, autophagy inducing effect of SA has been reported by Zhao et al. (2021) in HepG2 and SMMC-7721 cells
eff↑, Beclin, Atg 5 increased and expression of p62 decreased in SA along with cisplatin treated HepG2 and SMMC-7721 cells
angioG↓, SA has been demonstrated to inhibit angiogenesis, cell invasion and metastasis in cancer cells
TumCI↓,
TumMeta↓,
EMT↓, SA (10 mM) treated cells showed decreased protein expression of EMT related proteins such as vimentin, MMP-9, MMP-2, and Snail and increased expression of E-cadherin in PANC-1 and SW1990 cell lines.
Vim↓,
MMP9↓,
MMP2↓,
Snail↓,
E-cadherin↑,
p‑Akt↓, SA treatment downregulated phosphorylated AKT and Gsk-3β in PANC-1 and SW1990 prostate cancer cell lines.
GSK‐3β↓,
TumCP↓, SA can inhibit cell proliferation in prostate cancer
ChemoSen↑, SA acts in collaboration with other chemotherapeutic agents to improve treatment sensitivity
Remission↑, tumor remission rate in the MLT group was significantly higher than that in the control group
OS↑, MLT group had an overall survival rate of 28.24% (n=294/1,041), which was greatly increased compared with the control group (RR =2.07; 95% CI, 1.55–2.76; P<0.00001; I2=55%)
neuroP↑, MLT could effectively reduce the incidence of neurotoxicity
VEGF↓, by the downregulation of vascular endothelial growth factor (VEGF)
KISS1↑, MLT could suppress the metastasis of triple-negative breast cancer by inducing KISS1 expression
TumCP↓, MLT can significantly inhibit the proliferation of cancer cells
ChemoSideEff↓, while reducing the incidence of side effects in chemotherapy or radiotherapy
radioP↑, In the 20 randomized trials included, MLT was beneficial to reduce multiple side effects of radiotherapy and chemotherapy
Dose∅, mostly 20 mg/day and taken orally and taken at night, respectively
*ROS↓, Preclinical experimental research has confirmed that MLT was capable of scavenging ROS and repairing damaged DNA to exert antitumor effects
DNArepair↑,
ROS↑, The mechanisms of MLT exerting antitumor effect might involve with other pathways, such as antiangiogenesis and pro-oxidant
Dose∅, dosage of melatonin used in the 8 included RCTs was 20 mg orally, once a day.
Remission↑, Melatonin significantly improved the complete and partial remission (16.5 vs. 32.6%; RR = 1.95, 95% CI, 1.49-2.54; P < 0.00001)
OS↑, as well as 1-year survival rate (28.4 vs. 52.2%; RR = 1.90; 95% CI, 1.28-2.83; P = 0.001)
radioP↑, dramatically decreased radiochemotherapy-related side effects
Showing Research Papers: 1 to 50 of 80
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 80
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 1, Catalase↓, 1, ENOX2↓, 1, Ferroptosis↑, 1, GSH↓, 1, GSH↑, 1, GSTs↓, 1, HO-1↓, 1, HO-2↓, 1, lipid-P↓, 1, lipid-P↑, 1, NRF2↓, 2, OXPHOS↓, 1, ROS↓, 2, ROS↑, 26, ROS⇅, 3, SIRT3↓, 1, Trx↓, 1, TrxR↓, 4, TrxR1↓, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 2, ATP↓, 1, CDC25↓, 1, MMP↓, 8, mtDam↑, 1, OCR↓, 1, OCR↑, 1, SDH↓, 1, XIAP↓, 2,
Core Metabolism/Glycolysis ⓘ
12LOX↓, 1, ALAT↝, 1, AMPK↑, 2, citrate↓, 1, cMyc↓, 1, CPT1A↓, 1, CYP3A4↓, 1, ECAR↝, 1, ECAR∅, 1, FASN↑, 1, GlucoseCon↓, 2, Glycolysis↓, 4, HK2↓, 1, KeyT↑, 1, lactateProd↓, 2, LDH↓, 1, NADPH↓, 1, PDH↓, 1, p‑PDH↑, 1, PDK1?, 2, PDK1↓, 4, PDKs↓, 2, p‑PDKs↓, 1, PFK1↓, 1, PFK2?, 1, PKM2↓, 2, SIRT1↓, 3, TCA↓, 2, Warburg↓, 2, β-oxidation↓, 1,
Cell Death ⓘ
Akt↓, 4, Akt↑, 1, p‑Akt↓, 3, Apoptosis↑, 10, Bak↑, 2, BAX↑, 5, Bax:Bcl2↑, 5, Bcl-2↓, 5, Bcl-xL↓, 2, BID↑, 1, BIM↑, 2, Casp↑, 3, Casp2↑, 1, Casp3↑, 10, Casp7↑, 1, Casp8↑, 2, Casp9↑, 6, Chk2↑, 1, CK2↓, 1, Cyt‑c↑, 5, Diablo↑, 1, Fas↑, 1, Ferroptosis↑, 1, iNOS↓, 3, MAPK↑, 1, Mcl-1↓, 2, MDM2↓, 1, MLKL↑, 1, p‑MLKL↓, 1, Myc↓, 1, Necroptosis↑, 1, NOXA↑, 1, PUMA↑, 1, survivin↓, 2, Telomerase↓, 3,
Transcription & Epigenetics ⓘ
H3↓, 1, KISS1↑, 1, tumCV↓, 2,
Protein Folding & ER Stress ⓘ
eIF2α↑, 1, p‑eIF2α↑, 1, HSP70/HSPA5↑, 1, HSP90↓, 1,
Autophagy & Lysosomes ⓘ
LC3B↑, 1, LC3II↑, 1, p62↓, 1, p62↑, 1, TumAuto↑, 2, TumAuto↝, 1,
DNA Damage & Repair ⓘ
CHK1↓, 1, DNA-PK↑, 1, DNAdam↓, 1, DNAdam↑, 5, DNArepair↑, 1, DNMTs↓, 1, P53↑, 7, p‑P53↑, 1, ac‑P53↑, 1, p‑PARP↑, 1, cl‑PARP↑, 7, PCNA↓, 1, SIRT6↓, 1, SIRT6↑, 1, γH2AX↑, 1, p‑γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 1, CDK4↑, 1, cycD1/CCND1↓, 5, cycE/CCNE↓, 1, P21↑, 5, RB1↑, 1, p‑RB1↓, 2, TumCCA↓, 1, TumCCA↑, 8,
Proliferation, Differentiation & Cell State ⓘ
CDK8↓, 1, CSCs↓, 2, EMT↓, 6, ERK↓, 3, ERK↑, 2, p‑ERK↓, 1, FOXO3↑, 1, GSK‐3β↓, 1, p‑GSK‐3β↓, 1, HDAC↓, 1, HDAC1↓, 1, IGF-1↓, 1, IGF-1R↓, 3, p‑IGF-1R↓, 1, mTOR↓, 1, mTOR⇅, 1, Nanog↓, 1, NOTCH↓, 1, OCT4↓, 1, PI3K↓, 3, PTEN↑, 6, STAT3↓, 5, p‑STAT3↓, 2, TumCG↓, 5, TumCG↑, 1, Wnt/(β-catenin)↓, 2,
Migration ⓘ
AntiAg↝, 1, Ca+2↓, 1, Ca+2↑, 2, Ca+2↝, 1, i-Ca+2↓, 1, E-cadherin↑, 3, FAK↓, 1, p‑FAK↓, 2, MMP2↓, 5, MMP9↓, 6, MMPs↓, 2, N-cadherin↓, 1, p‑pax↓, 1, PKCδ↓, 1, RIP3↑, 1, p‑RIP3↑, 1, SMAD3↓, 1, Snail↓, 3, TGF-β↓, 1, TSC1↑, 1, TSP-1↑, 1, TumCI↓, 2, TumCMig↓, 3, TumCP↓, 6, TumMeta↓, 3, Twist↓, 1, Vim↓, 3, β-catenin/ZEB1↓, 4,
Angiogenesis & Vasculature ⓘ
angioG↓, 6, angioG↑, 2, EGFR↓, 1, Endoglin↑, 1, EPR↑, 1, Hif1a↓, 7, PHDs↓, 1, VEGF↓, 5,
Barriers & Transport ⓘ
BBB↑, 1, GLUT1↓, 2, NHE1↓, 1,
Immune & Inflammatory Signaling ⓘ
COX1↓, 1, COX2↓, 6, Igs↓, 1, Igs↑, 1, IL1↑, 1, IL10↓, 1, IL10↑, 1, IL1β↓, 1, IL6↓, 2, Inflam↓, 3, JAK↓, 1, NF-kB↓, 6, PD-L1↓, 1, T-Cell↑, 1, T-Cell↝, 1, TNF-α↓, 1, TNF-α↑, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1, CDK6↓, 2, CDK6↑, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 2, BioAv↑, 1, BioAv∅, 1, ChemoSen↑, 7, CYP1A2↓, 1, CYP2C9↓, 1, Dose?, 3, Dose↓, 1, Dose↝, 1, Dose∅, 53, eff↓, 7, eff↑, 39, eff↝, 1, Half-Life∅, 3, RadioS↑, 5, selectivity↓, 1, selectivity↑, 13,
Clinical Biomarkers ⓘ
ALAT↝, 1, ALP↓, 1, ALP↝, 1, AR↓, 1, AST↝, 1, BG↓, 1, E6↓, 1, E7↓, 1, EGFR↓, 1, IL6↓, 2, LDH↓, 1, Myc↓, 1, PD-L1↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 3, AntiTum↑, 1, cachexia↓, 1, ChemoSideEff↓, 2, NDRG1↑, 1, neuroP↑, 1, OS↑, 7, QoL∅, 1, radioP↑, 2, Remission↓, 1, Remission↑, 3, toxicity↓, 2, toxicity∅, 3, TumVol↓, 1, TumW↓, 1, Weight↑, 2,
Total Targets: 264
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
ROS↓, 3,
Core Metabolism/Glycolysis ⓘ
ACLY↓, 1, LDH↓, 1, SREBF2↓, 1,
Transcription & Epigenetics ⓘ
other↑, 1,
Proliferation, Differentiation & Cell State ⓘ
HMGCR↓, 1,
Synaptic & Neurotransmission ⓘ
MAOA↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv?, 1, BioAv↓, 6, BioAv↑, 2, BioAv↝, 3, BioEnh↑, 1, Dose∅, 7, eff↓, 1, eff↑, 4, Half-Life∅, 3,
Clinical Biomarkers ⓘ
LDH↓, 1,
Functional Outcomes ⓘ
toxicity↓, 3, toxicity∅, 3,
Total Targets: 19
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#:6
wNotes=on sortOrder:rid,rpid
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