P21 Cancer Research Results

P21, P21: Click to Expand ⟱

Source:

Type: Proapototic

cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21

Scientific Papers found: Click to Expand⟱

726-

Bor,

Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells—An Issue Still Open

Review,

NA,

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↓,

5694-

BRU,

Brusatol overcomes chemoresistance through inhibition of protein translation

in-vitro,

Lung,

A549

NRF2↓, brusatols mode of action is not through direct inhibition of the NRF2 pathway, but through the inhibition of both cap-dependent and cap-independent protein translation, which has an impact on many short-lived proteins, including NRF2.
P53↓, After a 4 h treatment, both brusatol and bruceantin reduced the protein levels of NRF2, p53, and p21 in a dose-dependent manner
P21↓,

5705-

Brut,

A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apcam1137)

in-vivo,

CRC,

rats

Risk↓, Rats treated with BJe showed a significant dose-related reduction in the colon preneoplastic lesions mucin-depleted foci (MDF). strategy to prevent CRC in high-risk patients.
TumMeta↓, Colon and small intestinal tumours were also significantly reduced in rats supplemented with 70 mg/kg of BJe.
Apoptosis↑, Moreover, in colon tumours from rats fed with 70 mg/kg BJe, apoptosis was significantly higher than in controls.
COX2↓, significant down-regulation of inflammation-related genes (COX-2, iNOS, IL-1β, IL-6 and IL-10 and Arginase 1).
iNOS↓,
IL1β↓,
IL6↓,
IL10↓,
P53↑, Up-regulation of p53 and down-regulation of survivin and p21 genes was also observed.
P21↓,
survivin↓,
chemoPv↑, These data indicate a strong chemopreventive activity of BJe that, at least in part, is due to its pro-apoptotic and anti-inflammatory actions.
*Inflam↓,

1318-

EMD,

Aloe-emodin Induces Apoptosis in Human Liver HL-7702 Cells through Fas Death Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen Species

in-vitro,

Nor,

HL7702

*TumCCA↑, induced S and G2/M phase cell cycle arrest
*ROS↑,
*MMP↓,
*Fas↑,
*P53↑,
*P21↓,
*Bax:Bcl2↑,
*cl‑Casp3↑,
*cl‑Casp8↑,
*cl‑Casp9↑,
*cl‑PARP↑,

2828-

FIS,

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

Review,

Var,

*neuroP↑, As a hydrophobic agent, FIS readily penetrates cell membranes and accumulates in cells to exert neuroprotective, neurotrophic and antioxidant effects
*antiOx↑,
*Inflam↓, FIS treatment may include alleviating inflammation, cell apoptosis and oxidative stress
RenoP↑, alleviates cell apoptosis and inflammation in acute kidney injury
COX2↓, FIS induces apoptosis in various tumor cells by, for example, inhibiting cyclooxygenase-2, inhibiting the Wnt/EGFR/NF-κB pathway, activating the caspase-3 cascade
Wnt↓,
EGFR↓,
NF-kB↓,
Casp3↑,
Ca+2↑, activating the caspase-3 and Ca2+ dependent endonuclease, and activating the caspase-8/caspase-3 dependent pathway via ERK1/2.
Casp8↑,
TumCCA↑, FIS controls the cell cycle and inhibits cyclin-dependent kinases (CDKs) in human cancer cell lines,
CDK1↓,
PI3K↓, by inhibition of PI3K/Akt/mTOR signaling [20], mitogen-activated protein kinases (MAPK) [21], and nuclear transcription factor (NF-κB)
Akt↓,
mTOR↓,
MAPK↓,
*P53↓, FIS inhibits aging by reducing p53, p21 and p16 expression in mouse and human tissues
*P21↓,
*p16↓,
mTORC1↓, FIS induces autophagic cell death by inhibiting both the mTORC1 and mTORC2 pathways
mTORC2↓,
P53↑, FIS significantly increases the expression of p53 and p21 proteins and lowers the levels of cyclin D1 [27,28], cyclin A, CDK4 and CDK2, thus contributing to cell-cycle arrest.
P21↑,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
BAX↑, FIS also increases Bax [27,28] and Bak [27] protein expression, but reduces the levels of Bcl-2 [27,28], Bcl-xL [27] and PCNA [28], and then starts the mitochondrial apoptotic pathway.
Bcl-2↓,
PCNA↓,
HER2/EBBR2↓, FIS reduces HER2 tyrosine phosphorylation in a dose-dependent manner and aids in proteasomal degradation of HER2 rather than lysosomal degradation
Cyt‑c↑, FIS cells causes destabilization of the mitochondrial membrane and an increase in cytochrome c levels, which is consistent with the loss of mitochondrial membrane integrity.
MMP↓,
cl‑Casp9↑,
MMP2↓, FIS reduces the enzymatic activity of both MMP-2 and MMP-9.
MMP9↓,
cl‑PARP↑, cell membrane, mitochondrial depolarization, activation of caspase-7, -8 and -9, and cleavage of PARP
uPA↓, interestingly, the promoter activity of the uPA gene is suppressed by FIS
DR4↑, induces upregulation of DR4 and DR5 death receptor expression in a dose-dependent manner
DR5↑,
ROS↓, FIS induces an increase in intracellular Ca2+ but reduces the production of ROS in WEHI-3 cells (myelomonocytic leukemia)
AIF↑, It also increases the levels of caspase-3 and AIF mRNA, but also increases necrosis markers including RIP3 and PARP1
CDC25↓, FIS reduces the expression of cdc25a, but increases the expression of p-p53, Chk1, p21 and p27, which may lead to a G0/G1 arrest.
Dose↑, FIS in concentrations from 0 to 10 μM does not affect cell viability; however, its use at concentrations of 20–40 μM significantly reduces the viability of lung cancer cells
CHOP↑, CaKi : FIS induces upregulation of CHOP expression and ROS production
ROS↑, NCI-H460 :FIS increases the ER stress signaling FIS increases the level of mitochondrial ROS FIS induces mitochondrial Ca2+ overloading and ER stress FIS induced ER stress-mediated cell death via activation of the MAPK pathway
cMyc↓, FIS influences proliferation related genes such as cyclin D1, c-myc and cyclooxygenase (COX)-2 by downregulating them.
cardioP↑, cardioprotective activity

4786-

Lyco,

Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines

in-vitro,

BC,

MDA-MB-468

10.3 μM

in-vitro,

BC,

MCF-7

29.9 μM

in-vitro,

BC,

SkBr3

22.8 μM

TumCP↓, dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma.
TumCCA↑,
cl‑PARP↑, demonstrable cleavage of PARP.
ERK↑, Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines
cycD1/CCND1↓,
P21↓,
p‑Akt↓, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax
mTOR↓,
BAX↑,
AntiCan↑, data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells
Risk↓, Lycopene has been shown to reduce the risk of overall breast cancer more prominently than other carotenoids

198-

MFrot,

MF,

Biological effects of rotating magnetic field: A review from 1969 to 2021

Review,

Var,

AntiCan↑, RMF can inhibit the growth of various types of cancer cells in vitro and in vivo and improve clinical symptoms of patients with advanced cancer.
breath↑, 0.4T, 7Hz RMF was applied to treat 13 advanced non-small cell lung cancer patients (2 h/day, 5 days per week, for 6–10 weeks)
Pain↓, Decreased pleural effusion (2 patients, 15.4%), remission of shortness of breath (5 patients, 38.5%), relief of cancer pain (5 patients, 38.5%), increased appetite (6 patients, 46.2%), improved physical strength (9 patients, 69.2%), regular bowel mov
Appetite↑,
Strength↑,
BowelM↑,
TumMeta↓, The same RMF (2 h/day, for 43 days) can also suppress the growth and metastasis of B16-F10 cells in vivo
TumCCA↑, The up-regulated transcription of miR-34a induced cell proliferation inhibition, cell cycle arrest, and cell senescence by targeting E2F1/E2F3, two members of E2F family which are major regulators of the cell cycle,
ETC↓, 2h exposure) effectively inhibited the growth of two types of cultured brain cancer cells, glioblastoma cells and diffuse intrinsic pontine glioma cells. They found that the mitochondrial electron transport chain was significantly disturbed by RMF,
MMP↓, which caused loss of mitochondrial integrity, decreased mitochondrial carbon flux in cancer cells, and eventual cancer cell death (Sharpe et al., 2021).
TumCD↑,
selectivity↑, same group further reported that the same RMF can also selectively kill cultured human glioblastoma and non-small cell lung cancer cells, and leave normal cells unharmed
ROS↑, Mechanistic studies revealed that RMF can increase the mitochondrial ROS level, which further activated the caspase-3 and disturbed the electron fflow in the respiratory chain pathway in cancer cells. (Helekar et al., 2021).
Casp3↑,
TumCG↓, 0.4T, 7.5Hz RMF (2 h/day, for 5 days) inhibited the growth of mouse melanoma cell line B16–F10 in vitro,
TumCCA↑, and its mechanism involved cell cycle arrest and decomposition of chromatins.
ChrMod↑,
TumMeta↓, (2 h/day, for 43 days) can also suppress the growth and metastasis of B16–F10 cells in vivo,
Imm↑, benefiting from improved immune function, including decreased regulatory T cells, increased T cells, and dendritic cells
DCells↑,
Akt↓, inhibiting the activation of the AKT pathway (Tang et al., 2016). T
OS⇅, 51 women with advanced breast cancer underwent RMF treatment. The results showed that 27 patients among them achieved signicant therapeutic effects, and there were no side-effects
toxicity↓,
QoL↑, 13 advanced non-small cell lung cancer patients the quality of life was improved in different degrees. Median survival and 1-year survival rate was 50% and 100% longer
hepatoP↑, In addition, it seems that the RMF can also attenuate liver damage in mice bearing MCF7 and GIST-T1 cells (Zha et al., 2018)
Pain↓, The results showed that the RMF treatment reduced abdominal pain by 42.9% (9/21), nausea/vomiting by 19.0% (4/21), weight loss by 52.4% (11/21), ongoing blood loss by 9.5% (2/21), improved physical strength by 23.8% (5/21) and sleep quality by 19.0%
Weight↑,
Strength↑,
Sleep↑,
IL6↓, Furthermore, decreased levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) were observed
CD4+↑, it was discovered that macrophages and dendritic cells were activated, CD4+ T and CD8+ T lymphocytes increased, and the ratio of Th17/Treg was balanced.
CD8+↑,
Ca+2↑, effects of RMF were strongly associated with increased calcium tunnel activity and intracellular Ca2+ level in CNS
radioP↑, These results suggest that RMF may be helpful to alleviate the damage of hematopoietic function caused by radiotherapy and chemotherapy
chemoP↑,
*BMD↑, 0.4T, 8Hz RMF treatment (30min/day, for 30 days) along with calcium supplement, synergistically improved bone density
*AntiAge↑, In 2019, Xu et al. reported that a 4h exposure to a 0.2T, 4Hz RMF delayed the aging of human umbilical vein endothelial cells (HUVEC)
*AMPK↑, Mechanistic research revealed that RMF treatment increased the expression of AMPK while reducing the expression of p21, p53 and mTOR.
*P21↓,
*P53↓,
*mTOR↓,
*OS↑, They also discovered that the RMF (2 h/day, for 6, 10 or 14days) can prolong the health status lifespan of Caenorhabditis elegans.
*β-Endo↑, 0.1–0.8T, 0.33Hz RMF treatment signicantly increased the β-endorphin level in the blood of rabbits and humans (23 times higher than before). Moreover, it decreased serotonin (5-HT) in brains, small intestine tissue and serum of mice.
*5HT↓,

1311-

NarG,

Rad,

Naringenin sensitizes lung cancer NCI-H23 cells to radiation by downregulation of akt expression and metastasis while promoting apoptosis

in-vitro,

Lung,

H23

tumCV↓,
ROS↑,
Casp3↑,
p‑Akt↓,
Akt↓,
MMP2↓,
P21↓,

2035-

PB,

Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease

in-vitro,

Nor,

glial

in-vivo,

NA,

mice

*ROS↓, sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells
*Inflam↑,
*P21↓, Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins
*antiOx↑,
*GSH↑, protected nigral reduced glutathione
*NF-kB↓, attenuated nigral activation of NF-κB
*neuroP↑, These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.
*HDAC↓, Because NaPB is a known inhibitor of histone deacetylase (HDAC)
*iNOS↓, Similar to the inhibition of iNOS, NaPB dose-dependently inhibited the production of TNF-α and IL-1β protein in activated microglia
*TNF-α↓,
*IL1β↓,
*LDL↓, NaPB reduced the level of cholesterol in serum of mice by about 30%; and this reduction was comparable to that (∼29%) by the so-called cholesterol-lowering drug pravastatin
ROS↓, NaPB strongly inhibited MPP+-induced production of intracellular ROS

1672-

PBG,

The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers

Review,

BC,

ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

2430-

PBG,

The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation

in-vitro,

BC,

MDA-MB-231

TumCP↓, CP extract exhibited antiproliferative and cytotoxic effects on MDA MB-231 cells, what may be probably related to PI3K/Akt and ERK1/2 pathways.
TP53↓, decreased expression of apoptosis-related genes (TP53, CASP3, BAX and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, These results suggested that CP cytotoxic effects on MDA MB-231 cells might be associated with the intracellular ROS production
eff↓, CP-induced ROS generation was reduced after cotreatment with the antioxidant NAC, which increased the percentage of viable cells, suggesting that CP-induced necrotic-related cell death could be associated with ROS production
MMP↓, Necrosis death is associated with mitochondrial dysfunction and our propolis sample reduced the MMP and increased LDH levels.
LDH↑,
ATP↓, rupture of mitochondrial membrane, loss of adenosine triphosphate (ATP),
Ca+2↑, excessive ROS production, intracellular [Ca+2] elevation, osmotic shock,

3353-

QC,

Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells

in-vitro,

Oral,

KON

 0, 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, and 400 µg/mL

50ug/L @ 72h

in-vitro,

Nor,

MRC-5

tumCV↓, reduced the vitality of KON cells and had minimal effect on MRC cells.
selectivity↑, Owing to the appropriate dosages of quercetin needed to treat these diseases, normal cells do not exhibit any overtly harmful side effects.
TumCCA↑, quercetin increased the percentage of dead cells and cell cycle arrests in the S and G2/M phases.
TumCMig↓, quercetin inhibited KON cells’ capacity for migration and invasion in addition to their effects on cell stability and structure
TumCI↓,
Apoptosis↑, inducing apoptosis and preventing metastasis, quercetin was found to downregulate the expression of BCL-2/BCL-XL while increasing the expression of BAX.
TumMeta↓,
Bcl-2↓,
BAX↑,
TIMP1↑, TIMP-1 expression was upregulated while MMP-2 and MMP-9 were downregulated.
MMP2↓,
MMP9↓,
*Inflam↓, anti-inflammatory, anti-cancer, antibacterial, antifungal, anti-diabetic, antimalarial, neuroprotective, and cardioprotective properties.
*neuroP↑,
*cardioP↑,
p38↓, MCF-7 cells, quercetin successfully decreased the expression of phosphor p38MAPK, Twist, p21, and Cyclin D1
MAPK↓,
Twist↓,
P21↓,
cycD1/CCND1↓,
Casp3↑, directly aided by the significant increase in caspase-3 and − 9 levels and activities
Casp9↑,
p‑Akt↓, High quercetin concentrations also caused an inhibition of Akt and ERK phosphorylation
p‑ERK↓,
CD44↓, reduced cell division and triggered apoptosis, albeit to a lesser degree in CD44+/CD24− cells.
CD24↓,
ChemoSen↑, combination of quercetin and doxorubicin caused G2/M arrest in T47D cells, and to a lesser amount in cancer stem cells (CSCs) that were isolate
MMP↓, (lower levels of ΔΨ m), which is followed by the release of Cyto C, AIF, and Endo G from mitochondria, which causes apoptosis and ultimately leads to cell death.
Cyt‑c↑,
AIF↑,
ROS↑, Compared to the control group, quercetin administration significantly raised ROS levels at 25, 50, 100, 200, and 400 µg/mL.
Ca+2↑, increased production of reactive oxygen species and Ca2+, decreased levels of mitochondrial membrane potential (ΔΨ m),
Hif1a↓, Quercetin treatment resulted in a considerable downregulation of HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels in HOS cells.
VEGF↓,

3352-

QC,

A review of quercetin: Antioxidant and anticancer properties

Review,

Var,

*antiOx↑, Quercetin is considered to be a strong antioxidant due to its ability to scavenge free radicals and bind transition metal ions. T
*lipid-P↓, properties of quercetin allow it to inhibit lipid peroxidation
*TNF-α↓, Quercetin significantly inhibited TNF-α production and gene expression in a dose-dependent manner
*NF-kB↓, inhibiting the activation of NF-κβ,
*COX2↓, Quercetin also inhibits the enzymes cyclooxygenase
*IronCh↑, Quercetin also chelates ions of transition metals such as iron which can initiate the formation of oxygen free radicals
P53↓, Quercetin (248 microM) was found to down regulate expression of mutant p53 protein to nearly undetectable levels in human breast cancer cell lines.
TumCCA↑, Quercetin has been found to arrest human leukemic T-cells in the late G1 phase of the cell cycle.
HSPs↓, Quercetin has been found to inhibit production of heat shock proteins in several malignant cell lines, including breast cancer,[52] leukemia,[53] and colon cancer.[
P21↓, Quercetin (10 microM) has been found to inhibit the expression of the p21-ras oncogene in cultured colon cancer cell lines
RAS↓,
ER(estro)↑, Quercetin has been shown to induce ER II expression in both type I estrogen receptor positive (ER+) and type I estrogen receptor negative (ER-) human breast cancer cells
OS?, Animals treated daily with 40 mg/kg quercetin had a 20-percent increase in life span, while those treated with 160 mg/kg rutin had a 50% increase in life span.

2982-

RES,

The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1

in-vitro,

Melanoma,

MSTO-211H

IC50 for Res was 17 µM in MSTO-211H cells.

tumCV↓, Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM).
Apoptosis↑,
Sp1/3/4↓, significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels
p27↓, figure 4
P21↓,
cycD1/CCND1↓,
Mcl-1↓,
survivin↓,

2197-

SK,

Shikonin derivatives for cancer prevention and therapy

Review,

Var,

ROS↑, This compound accumulates in the mitochondria, which leads to the generation of reactive oxygen species (ROS), and deregulates intracellular Ca2+ levels.
Ca+2↑,
BAX↑, shikonin alone by increasing the expression of the pro-apoptotic Bax protein and decreasing the expression of the anti-apoptotic Bcl2 protein
Bcl-2↓,
MMP9↓, This treatment also inhibited metastasis by decreasing the expression of MMP-9 and NF-kB p65 without affecting MMP-2 expression.
NF-kB↓,
PKM2↓, Figure 4
Hif1a↓,
NRF2↓,
P53↑,
DNMT1↓,
MDR1↓,
COX2↓,
VEGF↓,
EMT↓,
MMP7↓,
MMP13↓,
uPA↓,
RIP1↑,
RIP3↑,
Casp3↑,
Casp7↑,
Casp9↑,
P21↓,
DFF45↓,
TRAIL↑,
PTEN↑,
mTOR↓,
AR↓,
FAK↓,
Src↓,
Myc↓,
RadioS↑, shikonin acted as a radiosensitizer because of the high ROS production it induced.

2411-

UA,

Ursolic acid in health and disease

Review,

Var,

Inflam↓, UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects
antiOx↑,
NF-kB↓, Colon cancer HCT116, HT29 20 μM for 8 hour ↓ NF-kB, Bcl-xL, Bcl-2, and cyclin D1
Bcl-xL↓,
Bcl-2↓,
cycD1/CCND1↓,
Ki-67↓, ↓ Ki67, CD31, STAT3, and EGFR, ↑ p53 and p21 mRNA expression
CD31↓,
STAT3↓,
EGFR↓,
P53↑,
P21↓,
HK2↓, MCF-7, MDA-MB-231 20 μM for 24 hours ↓ HK2, PKM2, ATP, and lactate ↓ pERK1/2, and depolarization of mitochondrial membrane potential, ↑ Nitric oxide and ATM
PKM2↓,
ATP↓,
lactateProd↓,
p‑ERK↓,
MMP↓,
NO↑,
ATM↑,
Casp3↑, T24 cancer cells ↑ Caspase 3 activity ↑ AMPK activation ↑ JNK activation
AMPK↑,
JNK↑,
FAO↑, 80 μM UA reduces triglyceride (TG) and cholesterol levels by increasing fatty acid oxidation and decreasing fatty acid synthesis in hepatocytes
FASN↓,
*GSH↑, ↑ Vitamin C, E, GSH, SOD, CAT, GPx, GST, and GR in heart
*SOD↑,
*Catalase↑,
*GPx↑,
*GSTs↑,
neuroP↑, This demonstrates that UA has a protective effect against various inflammatory conditions of the brain.

Showing Research Papers: 1 to 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 194

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 1, GPx↑, 1, GSH↑, 2, GSTs↑, 1, lipid-P↓, 1, ROS↓, 1, ROS↑, 1, SOD↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, LDL↓, 1,

Cell Death ⓘ

Bax:Bcl2↑, 1, cl‑Casp3↑, 1, cl‑Casp8↑, 1, cl‑Casp9↑, 1, Fas↑, 1, iNOS↓, 1,

DNA Damage & Repair ⓘ

p16↓, 1, P53↓, 2, P53↑, 1, cl‑PARP↑, 1,

Cell Cycle & Senescence ⓘ

P21↓, 4, TumCCA↑, 1,

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1, mTOR↓, 1,

Migration ⓘ

β-Endo↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1β↓, 1, Inflam↓, 3, Inflam↑, 1, NF-kB↓, 2, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

5HT↓, 1,

Clinical Biomarkers ⓘ

BMD↑, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, cardioP↑, 1, neuroP↑, 3, OS↑, 1,
Total Targets: 40

Scientific Paper Hit Count for: P21, P21

2 Propolis -bee glue
2 Quercetin
1 Boron
1 brusatol
1 Bruteridin(bergamot juice)
1 Emodin
1 Fisetin
1 Lycopene
1 Magnetic Field Rotating
1 Magnetic Fields
1 Naringin
1 Radiotherapy/Radiation
1 Phenylbutyrate
1 Resveratrol
1 Shikonin
1 Ursolic acid

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

P21 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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