PSA Cancer Research Results
PSA, prostate-specific antigen: Click to Expand ⟱
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Prostate-Specific Antigen (PSA) is a protein produced by both normal and malignant cells of the prostate gland. PSA testing is commonly used as a screening tool for prostate cancer.
Elevated levels of PSA in the blood can indicate the presence of prostate cancer, but they can also be caused by other conditions, such as benign prostatic hyperplasia (BPH) or prostatitis (inflammation of the prostate).
PSA is a clinical biomarker.
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Scientific Papers found: Click to Expand⟱
PSA↓, one patient
OS↑,
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,
PSA↓,
cycD1/CCND1↓, cyclinD1 and cyclinD2
cycE/CCNE↓,
CDK2↓,
CDK4/6↓,
P21↑,
AR↓,
*antiOx↑, ASX has protective effects on various diseases, such as Parkinson’s disease and cancer by showing potent antioxidant and anti-inflammatory properties.
*Inflam↓,
ChemoSen↑, Additionally, we determined that it exhibited synergistic action with cisplatin and significantly enhanced apoptotic cell death in PCa cells. (beware of dose required for this?)
E-cadherin↑, graphical abstract
N-cadherin↓,
VEGF↓,
cMyc↓,
PSA↓,
cl‑Casp3↑, ASTX improves the cisplatin induces caspase 3 cleavage and PARP1 activation
PARP1↑,
Dose↝, Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localised or locally advanced) nonmetastatic prostate cancer.
BioAv↑, Bicalutamide is slowly and saturably absorbed, but absorption is unaffected by food.
Half-Life↑, It has a long plasma elimination half-life (1 week) and accumulates about 10-fold in plasma during daily administration.
CYP3A4↓, In vitro data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a lesser extent, CYP2C9, 2C19 and 2D6.
PSA↓, Bicalutamide produces a dose-related decrease in prostate-specific antigen (PSA) at dosages < or = 150 mg/day.
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Review, |
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Review, |
AD, |
NA |
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Risk↓, Boron reduces prostate cancer incidence by up to 64%
serineP↓, Boric acid acts to inhibit serine proteases—it decreases PSA by 87% and reduces tumor size in a prostate cancer mouse model
PSA↓,
TumVol↓,
IGF-1↓, expression of IGF-1 (insulin-like growth factor type 1) was markedly reduced by boron treatment. Circulating blood levels of IGF-1 were not reduced in the treated mice, however.
*Mag↑, In situations of adequate calcium supply but deficient magnesium resources, boron appears to substitute or “pinch hit” for magnesium during the process of bone formation.
*Calcium↑, The effect of boron on raising plasma calcium levels may, in part, be due to its enhancing effect on vitamin D.1
*VitD↑,
*COX2↓, boron has been shown to inhibit cyclooxygenase (COX) and lipoxygenase (LOX).
*5LO↓,
*PGE2↓, leads to a decrease in prostaglandin E2 (PGE2)
*NF-kB↓, suppressing nuclear factor kappa beta (NfkappaB)
*cognitive↑, Since it is now commonly accepted that the routine use of NSAIDs significantly reduces the incidence of Alzheimer’s disease,31,32 it is not surprising that papers have been published on boron’s positive effect on cognitive function.
*hs-CRP↓, reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor μ (TNF-μ);
*TNF-α↓,
*SOD↑, raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase
*Catalase↑,
*GPx↑,
*cognitive↑, improves the brains electrical activity, cognitive performance, and short-term memory for elders; restricted boron intake adversely affected brain function and cognitive performance.
*memory↑, In humans, boron deprivation (<0.3 mg/d) resulted in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory.
*Risk↓, Boron-rich diets and regions where the soil and water are rich in boron correlate with lower risks of several types of cancer, including prostate, breast, cervical, and lung cancers.
*SAM-e↑,
*NAD↝, Boron strongly binds oxidized NAD+,76 and, thus, might influence reactions in which NAD+ is involved
*ATP↝,
*Ca+2↝, Because of its positive charge, magnesium stabilizes cell membranes, balances the actions of calcium, and functions as a signal transducer
HDAC↓, some boronated compounds are histone deacetylase inhibitors
TumVol↓,
IGF-1↓, expression of IGF-1 in the tumors was significantly reduced by boron treatment
PSA↓, Boronic acid has been shown to inhibit PSA activity.
Cyc↓, boric acid inhibits the growth of prostate-cancer cells both by decreasing expression of A-E cyclin
TumCMig↓,
*serineP↓, Boron exists in the human body mostly in the form of boric acid, a serine protease inhibitor.
HIF-1↓, shown to greatly inhibit hypoxia-inducible factor (HIF) 1
*ChemoSideEff↓, An in vitro study found that boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel
*VitD↑, greater production of 25-hydroxylase, and, thus, greater potential for vitamin-D activation
*Mag↑, Boron significantly improves magnesium absorption and deposition in bone
*eff↑, boron increases the biological half-life and bioavailability of E2 and vitamin D.
Risk↓, risk of prostate cancer was 52% lower in men whose diets supplied more than 1.8 mg/d of boron compared with those whose dietary boron intake was less than or equal to 0.9 mg/d.
*Inflam↓, As research into the chemistry of boron-containing compounds has increased, they have been shown to be potent antiosteoporotic, anti-inflammatory, and antineoplastic agents
*neuroP↑, In addition, boron has anti-inflammatory effects that can help alleviate arthritis and improve brain function and has demonstrated such significant anticancer
*Calcium↑, increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women.
*BMD↑, boron stimulates bone growth in vitamin-D deficient animals and alleviates dysfunctions in mineral metabolism characteristic of vitamin-D deficiency
*chemoP↑, may help ameliorate the adverse effects of traditional chemotherapeutic agents. boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel, an anticancer drug commonly used to treat breast, ovarian
AntiCan↑, demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma
*Dose↑, only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y.
*Dose↝, substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables
*BMPs↑, Boron was also found to increase mRNA expression of alkaline phosphatase and bone morphogenetic proteins (BMPs)
*testos↑, 1 week of boron supplementation of 6 mg/d, a further study by Naghii et al20 of healthy males (n = 8) found (1) a significant increase in free testosterone,
angioG↓, Inhibition of tumor-induced angiogenesis prevents growth of many types of solid tumors and provides a novel approach for cancer treatment; thus, HIF-1 is a target of antineoplastic therapy.
Apoptosis↑, Cancer cells, however, commonly overexpress sugar transporters and/or underexpress borate export, rendering sugar-borate esters as promising chemopreventive agents
*selectivity↑, In normal cells, the 2 latter, cell-destructive effects do not occur because the amount of borate present in a healthy diet, 1 to 10 mg/d, is easily exported from normal cells.
*chemoPv↑, promising chemopreventive agents
PSA↓, PSA activity is inhibited in vitro by boric acid
eff↑, newly developed boron-containing compounds have already demonstrated highly promising activities
*toxicity↓, Boronic acid/ester has been successfully incorporated into cancer treatments and therapy mainly due to its remarkable oxophilicity and low toxicity levels in the body
ROS↑, can trigger tumour microenvironmental abnormalities such as high levels of reactive oxygen species (ROS) and overexpressed enzymes
LAT↓, boron accumulation were observed to counterpart LAT-1 expression in a bone metastasis model of breast cancer
AntiCan↑, high concentration of boron in males reduces the probability of prostate cancer by 54% compared to males with low boron concentrations
AR↓, bortezomib
PSMB5↓, bortezomib
IGF-1↓, insulin-like growth factor 1 (IGF-1) in tumours was markedly reduced by boric acid.
PSA↓, exposure to both low-and high-dose boron supplementation, prostate-specific antigen (PSA) levels dropped by an average of 87%, while tumour size declined by an average of 31.5%
TumVol↓,
eff↑, phenylboronic acid is a more potent inhibitor than boric acid in targeting metastatic and proliferative properties of prostate cancer cells
Rho↓, RhoA, Rac1
Cdc42↓,
Ca+2↓, ER Ca+2 depletion occurred after the treatment of DU-145 prostate cancer cells with the physiological concentrations of boric acid
eff↑, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) against SCLC cell line using DMS-114 cells
TumVol↓, 38%
IGF-1↓, in tumors
PSA↓, 89%
PSA↓,
NAD↝, high affinity for the ribose moieties of NAD+
SAM-e↝, high affinity for S-adenosylmethione
PSA↓,
IGF-1↓,
Cyc↓, reduction in cyclins A–E
P21↓,
p‑MEK↓,
p‑ERK↓, ERK (P-ERK1/2)
ROS↑, induce oxidative stress by decreasing superoxide dismutase (SOD) and catalase (CAT)
SOD↓,
Catalase↓,
MDA↑,
GSH↓,
IL1↓, IL-1α
IL6↓,
TNF-α↓,
BRAF↝,
MAPK↝,
PTEN↝,
PI3K/Akt↝,
eIF2α↑,
ATF4↑,
ATF6↑,
NRF2↑,
BAX↑,
BID↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
Bcl-xL↓,
*Half-Life↝, (Boron) is excreted with a half-life of 21 hours, and is mostly eliminated with only a low level of accumulation in bone.
*eff↑, 13 subjects predetermined to be vitamin D deficient found that during a 60-day supplementation period with 6 mg boron/day, serum 25-hydroxyvitamin D levels rose by an average of 20%
PSA↓, one study using nude mice implanted with human prostate adenocarcinoma (LNCaP) cells found that boron supplementation reduced serum prostate-specific antigen (PSA) levels, and reduced tumor size and expression of IGF-1,
TumVol↓,
IGF-1↓,
*memory↓, Boron deprivation : results in significantly poorer performance on tasks involving eye-hand coordination, attention, and short-term memory (Penland 1994 and 1998).
*motorD↓,
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Pca, |
LNCaP |
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in-vitro, |
Pca, |
PC3 |
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in-vitro, |
PC, |
DU145 |
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AR↓, Phytonutrients synergistically inhibit androgen signaling
ARE/EpRE↑, x4 the sum of single ingredients
TumCP↓, Phytonutrients inhibit prostate cancer cell proliferation
PSA↓, combination
of three compounds such as in the case of curcumin, vitamin E
and the tomato extract showed a stronger synergistic effect than
each pair of compounds. The inhibition of PSA secretion
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in-vitro, |
Pca, |
PC3 |
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in-vitro, |
Pca, |
LNCaP |
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in-vitro, |
Pca, |
DU145 |
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in-vivo, |
NA, |
NA |
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TumCP↓, profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and -negative (PC-3, DU-145) prostate cancer cell lines
P53↑, increase of p53, p21, and Bax
P21↑,
BAX↑,
PSA↓, Capsaicin down-regulated the expression of not only prostate-specific antigen (PSA) but also AR
AR↓,
NF-kB↓, Capsaicin inhibited NF-kappa activation by preventing its nuclear migration
Proteasome↓, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha
TumVol↓, Capsaicin, when given orally, significantly slowed the growth of PC-3 prostate cancer xenografts
eff∅, However, our experiments using the three TRVP1-inhibitors capsazepine, ruthenium red, and SB366791, did not show any attenuation of the inhibitory activity of capsaicin.
PSA↓, A decrease in serum prostate specific antigen (PSA) was observed on the PolyE arm
other↑, A significant increase in plasma EGCG concentration was achieved in the treatment arm at 6 and 12 months
Risk↝, was well tolerated but did not reduce the likelihood of a subsequent PCa diagnosis in men with baseline HGPIN or ASAP.
AR↓, Curcumin significantly decreased AR expression at both the mRNA and protein level.
PSA↓, PSA levels tended to be reduced in the curcumin group
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Pca, |
22Rv1 |
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LNCaP |
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AR↓, results indicate that one of the potential mechanisms for the anticancer effect of the curcumin analogues was inhibition of AR pathways in human prostate cancer cells.
PSA↓, F10 and E10 resulted in a marked decrease in the level of PSA while the other compounds (curcumin, A10, B10 and C10) were less active.
Dose↑, However, in these studies, curcumin was used at relatively high concentrations, typically at >20 μM. I
PSA↓,
TGF-β↓, down regulation of the expression of TGF-β and an up-regulation of the bone morphogenic protein BMP-2 as a result of curcumin feeding
BMPs↑, BMP2,7
TumMeta↓, Curcumin Inhibits Prostate Cancer Bone Metastasis
PSA↓, The proportion of patients with PSA progression during the active curcumin treatment period (6 months) was significantly lower in the curcumin group than the placebo group (
Dose↝, two capsules, three times a day (1440 mg/day), for 6 months from the
beginning of ADT withdrawal.
PSA↓, Curcumin presumably synergizes with isoflavones to suppress PSA production in
prostate cells through the anti-androgen effects.
AR↓,
TumCG↓, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes.
PSA↓,
HK2↓,
AR↓, decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins.
Sp1/3/4↓, Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein.
HH↓, Figure 1
angioG↓,
TumCCA↑,
MDR1↓,
P-gp↓,
mTOR↓,
VEGF↓,
Smo↓,
Gli1↓,
OS↑, Itraconazole 400 mg daily was administered over 4 days every 2 weeks. A response rate of 44% was achieved, with a higher median overall survival time (1,047 days) compared with that previously reported in other studies, which ranged between 7-10mts
PSA↓, After the patient declined castration treatment, itraconazole was administered and the PSA level reduced by >50% in 3 months (300 mg twice daily)
Casp3↑, In LNCaP cells, it triggered apoptosis through the intrinsic pathway, promoting the activation of caspases 3 and 9, and decreasing mitochondrial potential (ΔΨ)
Casp9↑,
MMP↓,
AR↓, At sub-toxic concentrations, it downregulated ARs and PSA expression
PSA↓,
E-cadherin↑, Juglone upregulated the expression of the epithelial marker E-cadherin while reducing the mesenchymal factors N-caderin and vimentin.
N-cadherin↓,
Vim↓,
Akt↓, Furthermore, it synergistically inhibited the Akt/glycogen synthase kinase-3β (GSK-3β)/Snail axis that would physiologically promote E-cadherin repression and EMT induction
GSK‐3β↓,
EMT↑,
TumCI↓, decreased cell invasions by 56% and 80%, respectively, on BxPC-3 and PANC-1 cell lines.
MMP9↓, Juglone significantly dropped the protein level of MMP-9 and the vascular endothelial growth factor (VEGF) reporter Phactr-1 in both cell lines, while a drop of MMP-2 was evident only on BxPC-3
VEGF↓,
MMP2↓,
TumCCA↑, juglone promoted G1 cell-cycle arrest [94,95] and ROS-driven apoptosis
ROS↑,
Apoptosis↑,
GSH↓, Glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase protein levels diminished
Catalase↓,
SOD↓,
GPx↓,
DNAdam↑, juglone cytotoxicity is, at least partially, ascribed to DNA damage
γH2AX↑, high levels of γ-H2AX were registered when juglone was tested in combination with ascorbate.
eff↑, juglone’s anticancer profile (in terms of proliferation inhibition, cytotoxicity, and ROS induction) was highly improved by ascorbate [115], revealing an interesting synergistic activity between these two compounds
BAX↑, upregulation of many proteins involved in the intrinsic and extrinsic pathway, such as Bax, Cyt-c, Fas cell surface death receptor (Fas), Fas-ligand.
Fas↑,
Pin1↓, On U251 glioblastoma cells, juglone arrested cell growth by promoting apoptosis with the involvement of peptidyl-prolyl cis/trans isomerase (Pin1) inhibition [111]. Juglone is a well-known Pin1 inhibitor
eff↑, Our study shows that lycopene supplementation does not modify the main hallmarks of cancer, but it increases circulating lycopene concentration in patients under cancer therapy, which could have a positive impact on potential clinical and molecular o
cardioP↑, A systematic review and meta-analysis reported that tomato and lycopene supplementation have positive effects on cardiovascular risk factors
eff?, lycopene supplementation may have benefits in the oncology population during cancer treatment.
PSA↓, Lycopene supplementation improved PSA levels in patients with an intermediate risk of cancer
RenoP↑, Surprisingly, lycopene has been shown to improve renal makers of nephrotoxicity after cisplatin treatment
TumCP↓, Lycopene suppress the progression and proliferation
TumCCA↑, Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions.
Apoptosis↑,
*neuroP↑, the neuro-protective effect of lycopene, mediates the signaling pathways, by inhibiting NF-κB (nuclear factor-κB) and JNK protein (c-Jun N-terminal kinase), and activating Nrf2 (Nuclear factor erythroid 2-related factor 2) and BDNF (
*NF-kB↓,
*JNK↓,
*NRF2↑,
*BDNF↑,
*Ca+2↝, as well as keeping homeostasis by restoring intracellular Ca2+
*antiOx↑, most powerful and natural antioxidants, and its role in preventing prostate cancer.
*AntiCan↑,
*Inflam↓, Anti-inflammatory properties of lycopene depends on time, and it has been found to be through the decrease of inflammatory cytokines (i.e. IL1, IL6, IL8 and tumor necrosis factor-α (TNF-α)
*IL1↓,
*IL6↓,
*IL8↓,
*TNF-α↓,
NF-kB↓, lycopene increased the expression of BCO2 enzyme in an androgen-sensitive cell line that prevented cancer cell proliferation and reduced the NF-κB activity
DNAdam↓, 20 and 50 μM doses of lycopene had an effect on PC3 and DU145 cell lines in inducing apoptosis with DNA damages, and preventing cell growth and colony formation
PSA↓, lycopene twice a day for 3 weeks, showed that lycopene decreases the risk and growth of prostate cancer cells, and also a decrease in the level of PSA,
P53↓, down-regulation of p53, Cyclin-D1, and Nrf-2 have occurred after the incubation of prostate cancer cells with the lycopene received patient’s sera in comparison with placebo
cycD1/CCND1↓,
NRF2↓,
Akt2↓, treatment with lycopene in PC3 cancer cell lines was associated with down-regulation of AKT2 [
PPARγ↓, Another anti-proliferative effect of lycopene was done by increasing PPARγ-LXRα-ABCA1signaling molecules in protein and mRNA level
*Inflam↓, OC exhibits promising therapeutic potential against both inflammation and cancer.
AntiCan↑,
*COX2↓, OC was able to inhibit the enzymaticactivity of cyclooxigenease-2 (COX-1) and cyclooxigenease-2 (COX-2) with greater potencycompared to ibuprofen
*ROS↓, figure 3
*TNF-α↓,
*IL1β↓,
*iNOS↓,
TumCP↓, OC also effectively reduces cell proliferation and limits the production of the extracellular matrix in LX2 cells, suggesting its antifibrotic properties
*AntiAg↑, Healthy men: Anti-platelet effects
mTOR↓, Oleocanthalhas exhibited robust anti-proliferative effects in multiple breast cancer cell lines, accompanied by the downregulation of phosphorylated mTOR
STAT3↓, OC was shown to suppress STAT3 activity
ERK↓, OC was able to inhibit ERK1/2 and AKT phosphorylation and downregulate Bcl-2expression
p‑Akt↓,
Bcl-2↓,
ROS↑, OC effectively impeded the formation of cell colonies, triggered apoptosis, and incited the generation of intracellular ROS within cancer cells.
PSA↓, ↓PSA levels in mouse model
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, Inhibitory effects of quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt/(β-catenin)↓, wnt
PSA↓,
VEGF↓,
PARP↑,
Casp3↑,
Casp9↑,
DR5↑,
ROS⇅,
Shh↓,
P53↑, figure 1
P21↑, quercetin regulates p21 expression
EGFR↓,
TumCCA↑, quercetin has cell-specific anti-proliferative impacts via stimulation of cell cycle arrest at the G1 stage.
ROS↑, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↓,
TumCP↓,
selectivity↑, In breast cancer cells, quercetin inhibits cell proliferation without exerting any cytotoxic impact on normal breast epithelium
PDGF↓, figure 1
EGF↓,
TNF-α↓,
VEGFR2↓,
mTOR↓,
cMyc↓,
MMPs↓,
GRP78/BiP↑,
CHOP↑,
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Pca, |
LNCaP |
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in-vitro, |
Pca, |
LAPC-4 |
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PSA↓, quercetin inhibited the secretion of the prostate-specific, androgen-regulated tumor markers, PSA and hK2
AR↓, Quercetin inhibits the expression of AR protein
NKX3.1↓, Quercetin can also significantly down-regulate the expression of another prostate-specific gene, NKX3.1,
HK2↓, Quercetin inhibits PSA and hK2 secretion
AR↓,
PI3K/Akt↓, The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control.
miR-21↓,
STAT3↓,
BAD↓,
PRAS40↓,
GSK‐3β↓,
PSA↓,
NKX3.1↑,
Bax:Bcl2↑, a significantly increased ratio of Bax to Bcl-2 protein expression was observed in LAPC-4 cells by the combination treatment compared to Q alone, and a trend to increase in LNCaP cells
miR-19b↓,
miR-148a↓,
AMPKα↓,
TumCP↓, The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines.
chemoPv↑, combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer.
TumCMig↓, Enhanced inhibition of cell migration
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Pca, |
HEK293 |
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in-vitro, |
NA, |
22Rv1 |
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in-vitro, |
NA, |
C4-2B |
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hnRNPA1↓, quercetin downregulates hnRNPA1 expression
PSA↓,
NKX3.1↓,
FKBP5↓,
UBE2C↓,
AR-FL↓, FL AR
AR-V7↑, downregulates the expression of AR-V7, antagonizes androgen receptor signaling
AR↓, Quercetin downregulates androgen receptor signaling
eff↑, Quercetin resensitizes enzalutamide-resistant xenografts to enzalutamide in vivo
TumVol↓,
BioAv↓, The bioavailability of quercetin is low as it is present in glycosylated form, which can be readily metabolized by enzymes in the gut and liver, leading to low systemic concentrations in the body
BioAv↓, Resveratrol is poorly bioavailable, and that considered the major hindrance to exert its therapeutic effect, especially for cancer management
BioAv↓, at lower doses (25 mg per healthy subject) demonstrate that the mean proportion of free resveratrol in plasma was 1.7–1.9% with a mean plasma concentration of free resveratrol around 20 nM
Dose↑, Boocock and his colleagues studied the pharmacokinetic of resveratrol; in vitro data showed that minimum of 5 µmol/L resveratrol is essential for the chemopreventive effects to be elicited
eff↑, Despite the low bioavailability of resveratrol, it shows efficacy in vivo. This may be due to the conversion of both glucuronides and sulfate back to resveratrol in target organs such as the liver
eff↑, repeated administration of high doses of resveratrol generates a higher plasma concentration of parent and a much higher concentration of sulfate and glucuronide conjugates in the plasma
Dose↑, The doses tested in this study were 0.5, 1.0, 2.5 or 5.0 g daily for 29 days. No toxicity was detected, but moderate gastrointestinal symptoms were reported for 2.5 and 5.0 g doses
BioAv↑, the co-administration of piperine with resveratrol was used to enhance resveratrol bioavailability
ROS↑, Recent studies have shown that resveratrol increases ROS generation and decreases mitochondrial membrane potential
MMP↓,
P21↑, treatment decreased the viability of melanoma cells by activating the expression of both p21 and p27, which promoted cell cycle arrest.
p27↑,
TumCCA↑,
ChemoSen↑, Additionally, the use of resveratrol with cisplatin in malignant human mesothelioma cells (MSTO-211H and H-2452 cells) synergistically induces cell death by increasing the intracellular ROS level [64].
COX2↓, covers the down-regulation of the products of the following genes, COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA [93].
5LO↓,
VEGF↓,
IL1↓,
IL6↓,
IL8↓,
AR↓,
PSA↓,
MAPK↓, by preventing also the activation of the MAPK and PI3K/Akt signaling pathways, it suppresses HIF-1a and VEGF release in ovarian cancer cells of humans
Hif1a↓,
Glycolysis↓, Resveratrol was found to effectively impede the activation, invasion, migration and glycolysis of PSCs induced by reactive oxygen species (ROS) by down-regulating the expression of microRNA 21 (miR-21)
miR-21↓,
PTEN↑, also by increasing the phosphatise and tensin homolog (PTEN) protein levels
Half-Life↝, 25 mg/70 kg resveratrol administered to healthy human participants, the compound predominantly appeared in the form of glucuronide and sulfate conjugates in serum and urine and reached its peak concentrations in serum about 30 min after ingestion
*IGF-1↓, Brown and colleagues noted how a major decline in circulating insulin-like growth factor (IGF)-I as well as IGF-binding proteins (IGFBP-3) among healthy individuals can be credited to the intake of resveratrol
*IGFBP3↑,
Half-Life↓, Microactive® and Resveratrol SR and manufactured by Bioactives. This compound is capable of sustained release for over 12 h to increase intestinal residence time.
*Inflam↓, Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
*antiOx↑,
*AntiAg↑,
*chemoPv↑, Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis
ChemoSen↑,
BioAv↑, Compared to other known polyphenols, such as quercetin and catechin, trans-resveratrol is well absorbed much more efficiently following oral administration to humans
Half-Life↝, Compared to resveratrol, which has a plasma half-life of 8–14 min, the metabolites have a plasma half-life of about 9.2 hours
COX2↓, there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed
cycD1/CCND1↓, Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
MMP9↓, associated with decreased COX-2 and matrix metalloprotease-9 expression and suppression of NFκB activation
NF-kB↓,
Telomerase↓, Relatively high concentrations also substantially downregulate telomerase activity
PSA↓, Resveratrol downregulates PSA by a mechanism independent of changes in AR
MAPK↑, Resveratrol treatment of various prostate cells also accompanied the activation of MAPK signaling and an increase in cellular p53
P53↑,
TumCG↓, SW480 colon cancer cells and found RE to significantly decrease cell growth at a concentration of 31.25 µg/mL (48 h),
TumCP↓, Cell proliferation was dramatically decreased and cell cycle arrest was induced in HT-29 and SW480 c
TumCCA↑,
ChemoSen↑, RE enhanced the inhibitory effects of the chemotherapeutic drug 5-fluorouracil (5-FU) on proliferation and sensitized 5-FU resistant cells
NRF2↑, HCT116 ↑ Nrf2, ↑ PERK, ↑ sestrin-2, ↑ HO-1, ↑ cleaved-casp 3
PERK↑,
SESN2↑,
HO-1↑,
cl‑Casp3↑,
ROS↑, HT-29 ↑ ROS accumulation, ↑ UPR, ↑ ER-stress
UPR↑,
ER Stress↑,
CHOP↑, HT-29: ↑ ROS levels, ↑ HO-1 and CHOP
HER2/EBBR2↓, SK-BR-3: ↑ FOS levels, ↑ PARP cleavage, ↓ HER2, ↓ ERBB2, ↓ ERα receptor.
ER-α36↓,
PSA↓, LNCaP : ↑ CHOP, ↓ PSA production, ↑ Bax, ↑ cleaved-casp 3, ↓ androgen receptor expression
BAX↑,
AR↓,
P-gp↓, A2780: ↓ P-glyco protein, ↑ cytochrome c gene, ↑ hsp70 gene
Cyt‑c↑,
HSP70/HSPA5↑,
eff↑, This study noted that the rosemary essential oil was more potent than its individual components (α-pinene, β-pinene, 1,8-cineole) when tested alone at the same concentrations.
p‑Akt↓, A549: ↓ p-Akt, ↓ p-mTOR, ↓ p-P70S6K, ↑ PARP cleavage
p‑mTOR↓,
p‑P70S6K↓,
cl‑PARP↑,
eff↑, RE containing 10 µM equivalent of CA, or 10 µM CA alone (96 h) potentiated the ability of vitamin D derivatives to inhibit cell viability and proliferation, induce apoptosis and cell cycle arrest and increase differentiation of WEHI-3BD murine leukem
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LNCaP |
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ER Stress↑, A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress.
selectivity↑,
AR↓, rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153
TumCG↓, Rosemary extract modulates cell growth and induces cell cycle arrest in prostate cancer cell lines.
TumCCA↑,
CHOP↑, We observed an increase in overall protein expression of CHOP
PERK↓, decrease in PERK expression in prostate epithelial cells was observed following treatment with rosemary extract.
GRP78/BiP↑, rosemary extract induced BiP expression is essential for apoptosis.
PSA↓, AR and PSA is decreased and that of CHOP is increased in rosemary extract treated tissue lysates compared to lysates from control group animals.
AR↓, Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells.
Bcl-xL↓,
TumCP↓,
Glycolysis↓, Sulforaphane at 10 µM reduced the glycolysis and glycolytic capacity by 42% and 39%,
HK2↓, These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells.
PKA↓,
Hif1a↓, Sulforaphane and Capsaicin Reduced the Increased HIF-1α Levels Induced by Androgen Stimulus and Tip60 Overexpression
PSA↓, Sulforaphane and capsaicin prevented the activation of AR signaling (decreased nuclear AR levels and PSA levels)
ECAR↓, and glycolysis (decreased EACR; and HK and PK activities) induced by androgen and Tip60.
BioAv↑, increased sulforaphane bioavailability can be attained after the intake of sulforaphane-enriched broccoli sprout preparation (generated by quick steaming followed by myrosinase treatment) in mice
BioAv↓, Liposomal and methoxypoly (ethylene glycol)-poly(ε-caprolactone) microencapsulation increase capsaicin bioavailability by 3.34-fold and 6-fold respectively in rats
*toxicity↓, considering that the minimum lethal oral dose of capsaicin is 100 mg/Kg body weight in mice, its consumption could be safely increased
NRF2↑, chemopreventive properties that are thought to be due to potent upregulation of Nrf2
ChemoSideEff↓, chemopreventive properties
eff↑, combined SFN with taxol in treatment of prostate cancer cell line DU145, and observed that SFN potentiated the effects of low doses of taxol
TumCP↓,
Apoptosis↑,
TumCCA↑, induce G2/M cell cycle arrest in vitro and in vivo
eff↑, SFN positively enhanced bortezomib, lenalidomide, and conventional drugs, such as dexamethasone, doxorubicin, and melphalan in a synergistic manner
PSA↓, SFN has shown to significantly reduce levels of prostate-specific antigen (PSA) (44.4% SFN group vs. 71.8% in placebo)
P53↑, SFN activates various anti-cancer responses such as p53, ARE, IRF-1, Pax-6 and XRE while suppressing proteins involved in tumorigenesis and progression, such as HIF1α, AP-1 and CA IX
Hif1a↓, while suppressing proteins involved in tumorigenesis and progression, such as HIF1α, AP-1 and CA IX
CAIX↓,
chemoR↓, SFN has thus shown to reduce chemoresistance and may be a potential agent to be used in conjunction with chemotherapeutics
5HT↓, SFN downregulates 5-HT receptor expression in Caco-2 cells
hepatoP↑, well as hepatoprotective agents.
chemoP↑, silymarin could be beneficial to oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics.
*lipid-P↓, Silymarin has been shown to significantly reduce lipid peroxidation and exhibit anti-oxidant, antihypertensive, antidiabetic, and hepatoprotective effects
*antiOx↑,
tumCV↓, reduces the viability, adhesion, and migration of tumor cells by induction of apoptosis and formation of reactive oxygen species (ROS), reducing glutathione levels, B-cell lymphoma 2 (Bcl-2), survivin, cyclin D1, Notch 1 intracellular domain (NICD),
TumCMig↓,
Apoptosis↑,
ROS↑,
GSH↓,
Bcl-2↓,
survivin↓,
cycD1/CCND1↓,
NOTCH1↓,
BAX↑, as well as enhancing the amount of Bcl-2-associated X protein (Bax) level (
NF-kB↓, The suppression of NK-κB-regulated gene products (e.g., cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF), and interleukin-1 (IL-1)) mediates the anti-inflammatory effect of silymarin
COX2↓,
LOX1↓,
iNOS↓,
TNF-α↓,
IL1↓,
Inflam↓,
*toxicity↓, Silymarin is also safe for humans, hence at therapeutic doses patients demonstrated no negative effects at the high dose of 700 mg, three times a day, for 24 weeks
CXCR4↓, fig 2
EGFR↓,
ERK↓,
MMP↓, reduction in mitochondrial transmembrane potential due to an increase in cytosolic cytochrome complex (Cyt c) levels.
Cyt‑c↑,
TumCCA↑, Moreover, silymarin increased the percentage of cells in the gap 0/gap 1 (G0/G1) phase and decreased the percentage of cells in the synthesis (S)-phase,
RB1↑, concomitant up-regulation of retinoblastoma protein (Rb), p53, cyclin-dependent kinase inhibitor 1 (p21Cip1), and cyclin-dependent kinase inhibitor 1B (p27Kip1)
P53↑,
P21↑,
p27↑,
cycE/CCNE↓, and down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase 4 (CDK4), and phospho-Rb
CDK4↓,
p‑pRB↓,
Hif1a↓, silibinin inhibited proliferation of Hep3B cells due to simultaneous induction of apoptosis and prevented the accumulation
cMyc↓, Silibinin also reduces cellular myelocytomatosis oncogene (c-MYC) expression, a key regulator of cancer metabolism in pancreatic cancer cells
IL1β↓, Silymarin can also inhibit the production of inflammatory cytokines, such as interleukin-1beta (IL-1β), interferon-gamma (IFNγ),
IFN-γ↓,
PCNA↓, ilymarin suppresses the high proliferative activity of cells started with a carcinogen so that it significantly inhibits proliferating cell nuclear antigen (PCNA) and cyclin D1 labeling indices
PSA↓, In another patent, S. marianum has been used as an estrogen receptor β-agonist and an inhibitor of PSA for treating prostate cancer
CYP1A1↓, Silymarin prevents the expression of CYP1A1 and COX-2
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16𝜇g/mL
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway
Half-Life↝, The half-life of selenite was 18.5 hours.
OS↑, Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression.
Pain↓, Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11–78%.
PSA↓,
GSH↓, selenite depletes cells of an important antioxidant, glutathione (GSH), and results in the generation of superoxide, a highly reactive and toxic radical that results in the generation of reactive oxygen species (ROS).
ROS↑,
selectivity↑, 1) prostate cancer cells are more sensitive to selenium (sodium selenite)-induced apoptosis than normal prostate epithelial cells
TumCG↓, 2) Selenite induces significant growth inhibition of well-established prostate cancer tumors in mice at doses that have no detectable toxicity when administered both ip and po, a
AR↓, 3) Selenite disrupts androgen receptor (AR) signaling, with inhibition of AR expression
Dose↑, This simulation reveals that only the higher dose levels (33 mg and 49.5 mg) reach the desired therapeutic range after a single dose.
ChemoSen↑, In another study of selenite (0.2 mg/kg per day for 7 days) in combination with chemotherapy, addition of selenite resulted in a significant increase in the percentage of apoptotic lymphoma cells and clinical response compared to patients treated wit
RadioS↑, sodium selenite was studied in 15 patients with advanced/metastatic tumors receiving concurrent sodium selenite with palliative radiation therapy.
AntiCan↑, Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo.
TumCP↓, Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis.
TumCMig↓,
Apoptosis↑,
cl‑PARP↑, Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
BAX↑, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2)
Bcl-2↓,
p‑Akt↓, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53.
p‑mTOR↓,
PI3K↓,
cMyc↓,
P53↑,
ROS↑, theaflavins inhibited Wt-p53 MCF-7 and ZR-75-1 cell migration in a dose-response manner while upregulating the levels of reactive oxygen species (ROS;
NF-kB↓, Theaflavin treatment inhibited the translocation of NF-kB/p65 to the nucleus of MCF-7 cells
MMP9↓, Additionally, the levels of pro-migratory proteins matrix metalloproteinase (MMP)-2 and MMP-9 were downregulated
MMP2↓,
TumVol↓, Histological examination of tumours revealed that the largest tumour in mice that received black tea extract was 40% smaller than the largest tumour in the control group
PSA↓, TF3 induced the greatest inhibition of testosterone-mediated androgen receptor expression while also suppressing testosterone-induced secretion of prostate-specific antigen (PSA).
TumCCA↑, Theaflavins isolated from black tea caused a dose-dependent inhibition of HT 460 human lung cancer cell viability, paired with G2/M phase cell cycle arrest and induced apoptosis
VEGF↓, F3 exhibited lower rates of proliferation (in a dose-dependent manner) and angiogenesis due to inhibition of VEGF secretion and HIF-1a protein
Hif1a↓,
CDK2↓, downregulation of CDK2 and CDK4 protein expression and CDK2 and cyclin E1 protein expression, respectively.
CDK4↓,
GSH↓, A decrease in cellular GSH content and an increase in ROS levels were observed with TF1 treatment.
Dose↑, The studies summarized in this review showed that, generally, cancer cells must be exposed to micromolar concentrations of theaflavins to observe anti-cancer effects.
BioAv↓, However, micromolar concentrations of theaflavins cannot be achieved through direct ingestion of the compounds themselves
BioAv↓, When two volunteers were administered 30 mg of theaflavins orally—the approximate equivalent of 30 cups of black tea—the maximum concentration of theaflavins detected in serum and urine after two hours were both in the femtomolar range
BioAv↑, Some success has been observed with the use of encapsulated nanoparticles to improve delivery of other poorly soluble polyphenols such as resveratrol, naringenin, curcumin, and carnosol [70,71,72]. This may offer a potential solution to improve the b
PSA↓,
ALP↓,
Showing Research Papers: 1 to 42 of 42
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 42
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
ARE/EpRE↑, 1, Catalase↓, 2, CYP1A1↓, 1, GPx↓, 1, GSH↓, 5, HO-1↑, 1, MDA↑, 1, NRF2↓, 1, NRF2↑, 3, ROS↓, 1, ROS↑, 11, ROS⇅, 1, SAM-e↝, 1, SOD↓, 2,
Mitochondria & Bioenergetics ⓘ
ATP↓, 1, EGF↓, 1, p‑MEK↓, 1, MMP↓, 4,
Core Metabolism/Glycolysis ⓘ
CAIX↓, 1, cMyc↓, 4, CYP3A4↓, 1, ECAR↓, 1, FASN↓, 1, Glycolysis↓, 2, HK2↓, 3, LAT↓, 1, NAD↝, 1, PI3K/Akt↓, 1, PI3K/Akt↝, 1, PPARγ↓, 1, PSMB5↓, 1, SIRT1↓, 1, SREBP1↓, 1,
Cell Death ⓘ
Akt↓, 2, p‑Akt↓, 3, APAF1↑, 1, Apoptosis↑, 6, BAD↓, 1, BAX↑, 6, Bax:Bcl2↑, 2, Bcl-2↓, 5, Bcl-xL↓, 2, BID↑, 1, Casp↑, 2, Casp3↑, 3, cl‑Casp3↑, 4, cl‑Casp7↑, 2, cl‑Casp8↑, 2, Casp9↑, 3, cl‑Casp9↑, 2, CK2↓, 2, Cyt‑c↑, 5, DR5↑, 1, Fas↑, 1, cl‑IAP2↑, 1, iNOS↓, 1, p‑JNK↓, 1, MAPK↓, 2, MAPK↑, 1, MAPK↝, 1, p27↑, 3, Proteasome↓, 1, survivin↓, 1, Telomerase↓, 3,
Kinase & Signal Transduction ⓘ
AMPKα↓, 1, HER2/EBBR2↓, 2, Sp1/3/4↓, 1,
Transcription & Epigenetics ⓘ
HATs↑, 1, miR-21↓, 3, other↑, 1, p‑pRB↓, 2, tumCV↓, 1,
Protein Folding & ER Stress ⓘ
ATF6↑, 1, CHOP↑, 3, eIF2α↑, 1, ER Stress↑, 2, GRP78/BiP↑, 2, HSP70/HSPA5↑, 1, HSPs↓, 1, PERK↓, 1, PERK↑, 1, UPR↑, 1,
Autophagy & Lysosomes ⓘ
SESN2↑, 1,
DNA Damage & Repair ⓘ
DNAdam↓, 1, DNAdam↑, 1, NKX3.1↓, 2, NKX3.1↑, 1, P53↓, 2, P53↑, 6, PARP↑, 1, cl‑PARP↑, 3, PARP1↑, 1, PCNA↓, 1, γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK1↓, 2, CDK2↓, 3, CDK4↓, 5, Cyc↓, 2, CycB/CCNB1↓, 1, cycD1/CCND1↓, 4, cycE/CCNE↓, 2, P21↓, 1, P21↑, 8, RB1↑, 1, TumCCA↑, 12,
Proliferation, Differentiation & Cell State ⓘ
AR-FL↓, 1, AR-V7↑, 1, BRAF↝, 1, CD44↓, 1, EMT↓, 2, EMT↑, 1, ERK↓, 4, p‑ERK↓, 1, Gli1↓, 1, GSK‐3β↓, 2, p‑GSK‐3β↓, 1, HDAC↓, 2, HH↓, 1, IGF-1↓, 7, IGFBP3↑, 2, mTOR↓, 3, p‑mTOR↓, 2, NOTCH↓, 1, NOTCH1↓, 1, p‑P70S6K↓, 1, PI3K↓, 2, PTEN↑, 1, PTEN↝, 1, Shh↓, 1, Smo↓, 1, STAT3↓, 3, TumCG↓, 5, Wnt↓, 1, Wnt/(β-catenin)↓, 1,
Migration ⓘ
5LO↓, 1, Akt2↓, 1, AntiAg↑, 1, CA↓, 1, Ca+2↓, 1, Ca+2↑, 2, cal2↑, 1, Cdc42↓, 1, CDK4/6↓, 1, E-cadherin↑, 4, ER-α36↓, 1, FAK↓, 2, hnRNPA1↓, 1, ITGB4↓, 1, miR-148a↓, 1, miR-19b↓, 1, miR-203↑, 1, MMP2↓, 3, MMP9↓, 4, MMPs↓, 2, N-cadherin↓, 2, PDGF↓, 2, PKA↓, 1, Rho↓, 1, serineP↓, 1, TGF-β↓, 2, TumCI↓, 2, TumCMig↓, 5, TumCP↓, 10, TumMeta↓, 2, uPA↓, 1, Vim↓, 2, Zeb1↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 3, ATF4↑, 1, EGFR↓, 4, HIF-1↓, 1, Hif1a↓, 7, LOX1↓, 1, VEGF↓, 9, VEGFR2↓, 1,
Barriers & Transport ⓘ
NHE1↓, 1, P-gp↓, 2,
Immune & Inflammatory Signaling ⓘ
COX2↓, 4, CXCR4↓, 1, IFN-γ↓, 1, IL1↓, 4, IL1β↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 1, NF-kB↓, 6, PD-L1↓, 1, PGE2↓, 1, PSA↓, 42, TNF-α↓, 3,
Synaptic & Neurotransmission ⓘ
5HT↓, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 19, CDK6↓, 1, FKBP5↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 9, BioAv↑, 5, chemoR↓, 1, ChemoSen↑, 6, Dose↑, 5, Dose↝, 3, eff?, 1, eff↑, 14, eff↝, 1, eff∅, 1, Half-Life↓, 2, Half-Life↑, 1, Half-Life↝, 4, MDR1↓, 1, RadioS↑, 1, selectivity↑, 4,
Clinical Biomarkers ⓘ
ALP↓, 1, AR↓, 19, BMPs↑, 1, BRAF↝, 1, EGFR↓, 4, HER2/EBBR2↓, 2, IL6↓, 2, PD-L1↓, 1, PSA↓, 42,
Functional Outcomes ⓘ
AntiCan↑, 5, cardioP↑, 2, chemoP↑, 2, chemoPv↑, 2, ChemoSideEff↓, 1, hepatoP↑, 2, OS↑, 3, Pain↓, 1, Pin1↓, 1, PRAS40↓, 1, RenoP↑, 1, Risk↓, 2, Risk↝, 1, toxicity↝, 1, toxicity∅, 1, TumVol↓, 8, UBE2C↓, 1,
Total Targets: 237
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 5, Catalase↑, 1, GPx↑, 1, lipid-P↓, 1, NRF2↑, 1, ROS↓, 1, SAM-e↑, 1, SOD↑, 1,
Mitochondria & Bioenergetics ⓘ
ATP↝, 1,
Core Metabolism/Glycolysis ⓘ
NAD↝, 1, SIRT1↑, 1,
Cell Death ⓘ
iNOS↓, 1, JNK↓, 1, MAPK↓, 1,
Proliferation, Differentiation & Cell State ⓘ
IGF-1↓, 1, IGFBP3↑, 1,
Migration ⓘ
5LO↓, 1, AntiAg↑, 2, Ca+2↝, 2, PKCδ↓, 1, serineP↓, 1, TIMP1↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 2, IL1↓, 1, IL1β↓, 1, IL6↓, 1, IL8↓, 2, Inflam↓, 7, NF-kB↓, 2, PGE2↓, 1, TNF-α↓, 3, VitD↑, 2,
Synaptic & Neurotransmission ⓘ
BDNF↑, 1,
Hormonal & Nuclear Receptors ⓘ
testos↑, 1,
Drug Metabolism & Resistance ⓘ
Dose↑, 1, Dose↝, 1, eff↑, 2, Half-Life↝, 1, selectivity↑, 1,
Clinical Biomarkers ⓘ
BMD↑, 1, BMPs↑, 1, Calcium↑, 2, hs-CRP↓, 1, IL6↓, 1, Mag↑, 2, VitD↑, 2,
Functional Outcomes ⓘ
AntiCan↑, 1, chemoP↑, 1, chemoPv↑, 2, ChemoSideEff↓, 1, cognitive↑, 2, memory↓, 1, memory↑, 1, motorD↓, 1, neuroP↑, 2, Risk↓, 1, toxicity↓, 3,
Total Targets: 57
Scientific Paper Hit Count for: PSA, prostate-specific antigen
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#:264 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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