pRB Cancer Research Results

pRB, retinoblastoma protein: Click to Expand ⟱

Source: Tumor suspressor

Type:

pRB, or retinoblastoma protein, is a crucial tumor suppressor that plays a significant role in regulating the cell cycle. It is encoded by the RB1 gene, and its primary function is to control the progression of cells from the G1 phase to the S phase of the cell cycle. When functioning properly, pRB binds to and inhibits E2F transcription factors, which are necessary for the expression of genes required for DNA synthesis and cell division.
pRB is often found to be downregulated or functionally inactivated due to mutations in the RB1 gene or through other mechanisms.

Scientific Papers found: Click to Expand⟱

2640-

Api,

Apigenin: A Promising Molecule for Cancer Prevention

Review,

Var,

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/BIRC3↑,
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↑,

5882-

CAR,

Carvacrol Promotes Cell Cycle Arrest and Apoptosis through PI3K/AKT Signaling Pathway in MCF-7 Breast Cancer Cells

in-vitro,

BC,

MCF7

200 µmol/L at 24 and 48 h

tumCV↓, Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h
TumCCA↑, significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells
pRB↓, A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest
cycD1/CCND1↓,
CDK4↓,
CDK6↓,
PI3K↓, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions.
p‑Akt↓,
Apoptosis↑,
Bcl-2↓,
BAX↑,

6640-

Cen,

Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells

in-vitro,

HCC,

Bel-7402

6.807 μM

in-vitro,

HCC,

QGY-7703

6.724 μM

TumCP↓, Our data indicated that asiaticoside significantly inhibited the proliferation of HCC cell lines QGY-7703 and Bel-7402 in a dose- and time-dependent manner.
Apoptosis↑, Moreover, asiaticoside significantly induced apoptosis in QGY-7703 and Bel-7402 cells.
TumCCA↑, Treatment with asiaticoside also caused G1 cell cycle arrest in QGY-7703 and Bel-7402 cells.
PI3K↓, mechanism underlying the effects of asiaticoside involves inhibiting the activity of the PI3K/Akt and MAPK/ERK pathways.
Akt↓,
MAPK↓,
ERK↓,
P-gp/ABCB1↓, We also found that asiaticoside reduces HCC cell drug resistance by downregulating the expression level of P-gp by decreasing the ROS level in chemotherapy-resistant HCC cells.
ROS↓,
p‑pRB↓, asiaticoside significantly downregulated the phosphorylation level of pRB and expression level of cyclin D1, and upregulated the p27 expression level, all in a dose-dependent manner
cycD1/CCND1↓,
p27/CDKN1B↑,

650-

EGCG,

Cellular thiol status-dependent inhibition of tumor cell growth via modulation of retinoblastoma protein phosphorylation by (-)-epigallocatechin

in-vitro,

NA,

TumCCA↑, in the G1 phase
p‑pRB↓,

649-

EGCG,

CUR,

PI,

Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets

Review,

Var,

*BioEnh↑, increase EGCG bioavailability is using other natural products such as curcumin and piperine
EGFR↓,
HER2/EBBR2↓,
IGF-1↓,
MAPK↓,
ERK↓, reduction in ERK1/2 phosphorylation
RAS↓,
Raf↓, Raf-1
NF-kB↓, Numerous investigations have proven that EGCG has an inhibitory effect on NF-κB
p‑pRB↓, EGCG were displayed to reduce the phosphorylation of Rb, and as a result, cells were arrested in G1 phase
TumCCA↑, arrested in G1 phase
Glycolysis↓, EGCG has been found to inhibit key enzymes involved in glycolysis, such as hexokinase and pyruvate kinase, thereby disrupting the Warburg effect and inhibiting tumor cell growth
Warburg↓,
HK2↓,
Pyruv↓,

7631-

Ins,

IP6,

Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate

Review,

Var,

other↑, Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways.
p‑pRB↓, Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle.
TumCCA↑,
PI3K↓, Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation.
Akt↓, Akt activation is severely impaired upon inositol addition
ERK↓, Downregulation of both Akt and ERK leads consequently to NF-kB inhibition and reduced expression of inflammatory markers (COX-2 and PGE2).
NF-kB↓,
COX2/PTGS2↓,
PGE2↓,
PSEN1/PS1↓, Remarkably, inositol-induced downregulation of presenilin-1 interferes with the epithelial-mesenchymal transition and reduces Wnt-activation, β-catenin translocation, Notch-1, N-cadherin, and SNAI1 release.
EMT↓,
Wnt↓,
β-catenin/ZEB1↓,
NOTCH1↓,
N-cadherin↓,
Snail↓,
E-cadherin↑, upregulating Focal Adhesion Kinase and E-cadherin and decreasing Fascin and Cofilin, two main components of pseudopodia, leading hence to invasiveness impairment.
fascin↓,
Cofilin↓,
MMPs↓, inositol-induced inhibition on metalloproteinases and ROCK1/2 release
ROCK1↓,
Dose↝, A mixed western diet provides the human adult with approximately 1 g of total inositol per day. it may be surmised that in western countries low-vegetable consumers may suffer from a relative deficiency of myo-Ins
other↝, InsP6 is often referred to as an antinutrient [20] responsible for iron deficiencies mostly in underdeveloped countries, it should be emphasized that InsP6 displays its antinutritional effects only when the diet is already deprived of trace elements
selectivity↑, specific for cancer cells, given that both InsP6 and myo-Ins did not promote apoptosis in normal cells.
*ROS↓, Myo-Ins counteracts oxidative damage in fish exposed to environmental stresses [114] and significantly inhibits systemic markers of oxidative stress in gynecological patients
*lipid-P↓, thus preventing formation of ADP-iron-oxygen complexes that trigger lipid peroxidation
ROS↑, antioxidant property of inositol is strictly context-dependent as, under specific conditions, both myo-Ins and InsP6 may increase free radical production
NK cell↑, inositol hexakisphosphate and myo-Ins enhance NK activity in mice treated with 1,2-dimethylhydrazine (DMH),
Imm↑, enhancement of immune function
TNF-α↓, InsP6 also modulates the transcription genes for TNF by decreasing it and its receptors in colon cancer cells
ChemoSen↑, inositol hexakisphosphate may potentiate the anticancer effects of conventional chemotherapy in preventing the successful development of cancer implants
Dose↑, Mild side effects (mostly represented by nausea or diarrhea) are reported in a small fraction of subjects, only for doses up to 12 g/day
toxicity↓,
QoL↑, where InsP6 plus myo-Ins treatment is associated with appreciable reduction in tumor burden and improved quality of life
chemoP↑, , if inositols were added along with conventional chemotherapy, colon cancer patients experienced significantly less side effects than controls, as reported in a pilot study
OS↑, Furthermore, prolonged survival and better quality of life have been obtained in some anecdotal cases of breast and lung cancer patients treated with InsP6 and myo-Ins
Dose↝, A study enrolling 26 smokers showed that myo-Ins in a daily dose up to 18 g/p.o. is safe and well tolerated, while inducing a significant regression of individual pulmonary dysplastic lesions
Insulin↓, downregulation of insulin levels, improved glucose utilization through the oxidative cycle, and inhibition of lipogenesis).
glucose↝,
lipoGen↓,
eff↑, There is a widespread consensus suggesting that InsP6 and myo-Ins act synergistically when added in association.

7726-

IP6,

Inositol hexaphosphate (IP6) blocks proliferation of human breast cancer cells through a PKCdelta-dependent increase in p27Kip1 and decrease in retinoblastoma protein (pRb) phosphorylation

in-vitro,

BC,

MCF7

AntiCan↑, Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate with demonstrated anti-proliferative and anti-cancer activity in mammary cells.
PKCδ↑, Treatment of MCF-7 human breast cancer cells with 2 mM IP6 for 24 h caused a 3.1-fold increase in the expression of anti-proliferative PKCdelta.
ERK↓, IP6 caused a decrease of Erk1/2 and Akt activity
Akt↓,
p27/CDKN1B↑, IP6 resulted in increased p27Kip1 protein levels and marked reduction of pRb phosphorylation.
p‑pRB↓,

7645-

IP6,

Ins,

Anticancer Properties of Inositol Hexaphosphate and Inositol: An Overview

AntiCan↑, A consistent and reproducible anticancer action of IP6 has been demonstrated in various experimental models.
TumCP↓, IP6 reduces cell proliferation, induces apoptosis and differentiation of malignant cells via PI3K, MAPK, PKC, AP-1 and NF-kappaB.
Apoptosis↑,
Diff↑,
p27/CDKN1B↓, down-regulates p27, inhibits pRB phosphorylation and cell cycle (23), reduces PI3K and consequently counteracts the activation of PKC/RAS/ERK pathway (23), downregulates Akt and ERK, leading to reduction of NF-kappaB and inhibition of inflammation.
pRB↓,
PI3K↓,
RAS↓,
ERK↓,
Akt↓,
NF-kB↓,
Inflam↓,
AntiTum↓, Studies demonstrated that continuous administration of 2% IP 6 in the drinking water, beginning 24 h after implantation of DU-145 prostate cancer cells, resulted in a 64% decrease in tumor burden

7690-

IP6,

Ins,

Inositol Hexaphosphate (IP6) and Colon Cancer: From Concepts and First Experiments to Clinical Application

Review,

Colon,

AntiCan↑, the striking and broad-spectrum anticancer activity of IP6, consistently demonstrated in different experimental models, has been in a spotlight of the scientific community dealing with the nutrition and cancer during the last several decades
Imm↑, Enhanced immunity and antioxidant properties also contribute to the tumor cell destruction.
antiOx↑,
TumCP↓, Along with this reduction in cell proliferation, rather normalization, IP6 induces differentiation and maturation of malignant cells,
Diff↑,
TumCG↓, Also, IP6 administered in drinking water was a potent inhibitor of in vivo growth of human prostate cancer xenografts in nude mice
eff↑, Synergistic cancer inhibition by IP6 when combined with inositol was observed in colon cancer
P21↓, IP6 downregulates p21 and p27, inhibits pRB phosphorylation and cell cycle progression [72], targets PI3K/Akt pathway and counteracts the activation of PKC/RAS/ERK pathway
p27/CDKN1B↓,
pRB↓,
TumCCA↑,
PI3K↓,
Akt↓,
PKCδ↓,
RAS↓,
ERK↓,
NF-kB↓, IP6 reduces NF-kappaB and inhibits inflammation
Inflam↓,
MMP9↓, IP6 and Ins were shown to inhibit the MMP-9
IronCh↑, Additionally, IP6 can remove the excess iron, which may facilitate and augment colorectal cancer IP6
NK cell↑, IP6 was shown to augment the activity of natural killer (NK) cells in vitro, and in vivo
selectivity↑, IP6 was shown that while it can sensitize cancer cells for treatment, at the same time can offer a protection to normal tissues.
ChemoSen↑, Furthermore, IP6 was shown to acts synergistically with standard chemotherapeutics. Cancer therapy recognizes the importance of using combination therapy with rationale to increase efficacy and decrease side-effects of conventional chemotherapy.
chemoP↑, when IP6 + Ins was given in combination with chemotherapy, side effects of chemotherapy, such as drop in leukocyte and platelet counts, nausea, vomiting, alopecia, were diminished and patients were able to perform their daily activities, shown mostly
toxicity↓, In a phase I clinical trial Ins was shown to be safe and well-tolerated
Remission↑, A patient with metastatic melanoma declined traditional therapy and opted to try the IP6 + Ins supplement only. He received a complete remission and remained in remission 3 years later.

7699-

IP6,

IP6: From Seeds to Science—A Natural Compound’s Path to Clinical Promise

Review,

Var,

*Iron∅, Early reports fueled concerns that high dietary phytate intake could contribute to mineral deficiencies, albeit without direct scientific evidence, particularly in populations lacking dietary diversity
ChemoSen↑, Preclinical and clinical research indicate that IP6, alone or in tandem with inositol (Ins), selectively targets cancer cells and enhances chemotherapy efficacy.
*cardioP↑, Growing evidence also suggests that IP6 plays a protective role in cardiovascular health, neurodegenerative disorders, and metabolic diseases
neuroP↑,
IronCh∅, confirmed that life-time consumption of IP6±Inositol did not cause any reduction in Ca, Mg, Fe, or Zn levels in the blood or bones of rats and mice
P21↓, IP6 downregulates cell cycle regulators such as p21 and p27, inhibits phosphorylation of retinoblastoma protein (pRB), and suppresses PI3K/protein kinase B (PI3K/Akt)
p27/CDKN1B↓,
p‑pRB↓,
PI3K↓,
Akt↓,
NF-kB↓, decreased NF-kB activity and inflammatory responses
Inflam↓,
TumW↓, After 12 days of treatment, IP6-treated mice exhibited a 3.4-fold lesser tumor weight as compared to controls
TumCI↓, figure 3
TumMeta↓,
Imm↑,
Diff↑,
selectivity↑, the growth of non-cancerous MCF-10A epithelial breast cells remained unaffected, further illustrating IP6’s capacity to differentiate between cancerous and normal cells
toxicity↓, Importantly, no adverse effects have been reported in studies administering IP6 or Ins to humans or animal models, even at high doses
RenoP↑, Plant-based food diets are often recommended to individuals with chronic kidney disease, where the protective effects of the diet are ascribed to IP6
QoL↑, Clinical trials, though still sparse, have yielded encouraging results regarding IP6’s synergistic enhancement of chemotherapy efficacy and improvement of patients’ quality of life.

5795-

MET,

Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes

Review,

AD,

Review,

Park,

Review,

Diabetic,

*AntiDiabetic↑, Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus.
*AMPK↑, acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver.
*glyC↓, It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism
*ROS↓,
*cardioP↑, hence minimizing the cardiovascular risks.
*neuroP↑, Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease.
*Half-Life↝, The plasma half-life of metformin is 2–3 hours, and the active duration is about 6–10hrs.
*toxicity↝, Metformin use for an extended period is linked to a deficiency of vitamin B12.
*BioAv↑, Absolute bioavailability 50–60% in healthy individuals
*glucose↓, Conventionally, it is quite established that metformin lowers blood glucose primarily by its action on the liver
*AGEs↓, Metformin decreases the synthesis of AGE (“Advanced Glycation End”) product formation and hyperglycaemic-induced ROS (“Reactive Oxygen Species”) production
AntiCan↑, There is growing evidence that metformin has anti-cancer effects based on clinical and preclinical studies.
Risk↓, reported that metformin use might decrease the risk of lung cancer within T2D patients as compared to other conventional agents.
TumCP↓, Several studies on cancer cell lines have observed that metformin treatment leads to inhibition of development and proliferation and induces apoptosis of the cancer cells
Apoptosis↑,
TumCCA↑, Metformin was found to block the cell cycle in the “G(0)/G(1)” phase
cycD1/CCND1↓, and this was observed with a sharp drop in the cyclin D1 levels, pRb phosphorylation, and elevated p27(kip) expression.
pRB↓,
p27/CDKN1B↓,
mTOR↓, as well as inhibits the mTOR pathway that is activated by insulin.
Casp↑, Metformin is also responsible for inducing caspase-dependent apoptosis along with c- JNK (“Jun N-Terminal Kinase”) activation, oxidative stress and mitochondrial depolarization.
ROS↑,
MMP↓,
ChemoSen↑, patients who received metformin along with the chemotherapy had better pathologic responses as compared to the group without metformin
*hepatoP↑, effects including cardioprotective, hepatoprotective, anti-malignant, and geroprotective effects
*CRM↑, mechanism behind the process of calorie restriction is a reduction in insulin
*Insulin↓,

3257-

PBG,

The Potential Use of Propolis as a Primary or an Adjunctive Therapy in Respiratory Tract-Related Diseases and Disorders: A Systematic Scoping Review

Review,

Var,

CDK4↓, CAPE also induces G1 phase cell arrest by lowering the expression of CDK4, CDK6, Rb, and p-Rb. M
CDK6↓,
pRB↓,
ROS↓, Artepillin C, a bioactive component of Brazilian green propolis, reduces oxidative damage markers, namely 4-HNE-modified proteins, 8-OHdG, malonaldehyde, and thiobarbituric acid reactive substances in lung tissues with pulmonary adenocarcinoma
TumCCA↑, Propolin, a novel component of prenylflavanones in Taiwanese propolis, was demonstrated to have anti-cancer properties. Propolin H induces cell arrest at G1 phase and upregulates the expression of p21
P21↑,
PI3K↓, Propolin C also inhibits PI3K/Akt and ERK-mediated epithelial-to-mesenchymal transition by upregulating E-cadherin (epithelial cell marker) and downregulating vimentin
Akt↓,
EMT↓,
E-cadherin↑,
Vim↓,
*COX2/PTGS2↓, bioactive compounds such as CAPE, galangin significantly reduce the activity of lung cyclooxygenase (COX) and myeloperoxidase (MPO), and malonaldehyde (MDA), TNF-α, and IL-6 levels, while increasing the activity of catalase (CAT) and SOD
*MPO↓,
*MDA↓,
*TNF-α↓,
*IL6↓,
*Catalase↑,
*SOD↑,
*AST↓, Chrysin also reduces the expression of oxidative and inflammatory markers such as aspartate transaminase (AST), alanine aminotransferase (ALT), IL-1β, IL-10, TNF-α, and MDA levels and increases the antioxidant parameters such as SOD, CAT, and GPx
*ALAT↓,
*IL1β↓,
*IL10↓,
*GPx↓,
*TLR4↓, propolis also inhibits the expression of Toll-like receptor 4 (TLR4), macrophage infiltration, MPO activity, and apoptosis of lung tissues in septic animals
*Sepsis↓,
*IFN-γ↑, CAPE also significantly increases IFN-γ
*GSH↑, propolis significantly increased the level of GSH and the histological appearances of propolis-treated bleomycin-induced pulmonary fibrosis rats.
*NRF2↑, CAPE significantly increases the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2)
*α-SMA↓, propolis significantly inhibits the expression of α- SMA, collagen fibers, and TGF-1β.
*TGF-β↓,
*IL5↓, Propolis also inhibits the expression of inflammatory cytokines and chemokines such as TNF-α, IL-5, IL-6, IL-8, IL-10, NF-kB, IFN-γ, PGF2a, and PGE2.
*IL6↓,
*IL8↓,
*PGE2↓,
*NF-kB↓,
*MMP9↓, downregulating the expression of TGF-1β, ICAM-1, α-SMA, MMP-9, IgE, and IgG1.

3369-

QC,

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects

Review,

Pca,

FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
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↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, 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↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP/DDIT3↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2/KDR/Flk1↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2/PTGS2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

84-

QC,

Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression

in-vitro,

Pca,

PC3

 25, 50, 75, 100 uM

P21↑, Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21.
cDC2↓, Cdc2/Cdk-1
CDK1↓, Cdc2/Cdk-1
CycB/CCNB1↓,
Casp3↑,
Bcl-2↓,
Bcl-xL↓, Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased.
BAX↑,
pRB↓,
TumCCA↑, Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis.
Apoptosis↑,

3290-

SIL,

A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents

Analysis,

Var,

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/PTGS2↓,
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/CDKN1B↑,
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

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1, Catalase↑, 1, GPx↓, 1, GSH↑, 1, Iron∅, 1, lipid-P↓, 2, MDA↓, 1, MPO↓, 1, NRF2↑, 1, ROS↓, 2, SOD↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

Insulin↓, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1, AMPK↑, 1, CRM↑, 1, glucose↓, 1, glyC↓, 1,

Cell Death(tgid=5) ⓘ

MAPK↓, 1,

Migration(tgid=13) ⓘ

MMP9↓, 1, PKCδ↓, 1, TGF-β↓, 1, α-SMA↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1, IFN-γ↑, 1, IL10↓, 1, IL1β↓, 1, IL5↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 1, NF-kB↓, 1, PGE2↓, 1, TLR4↓, 1, TNF-α↓, 1,

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1, BioEnh↑, 1, Half-Life↝, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1, IL6↓, 2,

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1, cardioP↑, 2, hepatoP↑, 1, neuroP↑, 1, toxicity↓, 1, toxicity↝, 1,

Infection & Microbiome(tgid=24) ⓘ

Sepsis↓, 1,
Total Targets: 48

Scientific Paper Hit Count for: pRB, retinoblastoma protein

5 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
3 Inositol
2 EGCG (Epigallocatechin Gallate)
2 Quercetin
1 Apigenin (mainly Parsley)
1 Carvacrol
1 Centella asiatica / Gotu kola → asiaticoside
1 Curcumin
1 Piperine
1 Metformin
1 Propolis -bee glue
1 Silymarin (Milk Thistle) silibinin

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

pRB Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Migration(tgid=13) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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