p27/CDKN1B Cancer Research Results

p27/CDKN1B, p27kip1: Click to Expand ⟱
Source:
Type:
The cyclin-dependent kinase (Cdk) inhibitor p27 regulates cell proliferation, cell motility and apoptosis, and is inactivated through various means in many types of human cancer.

CDKN1B - Cyclin-Dependent Kinase Inhibitor 1B / p27

Abbreviation: CDKN1B, p27, p27Kip1

Type: Cyclin-dependent kinase inhibitor / cell-cycle regulator

Function: CDKN1B/p27 inhibits cyclin-CDK complexes, particularly cyclin E-CDK2 and cyclin A-CDK2, thereby restricting G1/S cell-cycle progression. It also regulates differentiation, transcription, cytoskeletal organization, cell migration, and cellular responses to growth-factor signaling.

Cancer: ↕ Context-dependent, but predominantly tumor-suppressive. Reduced nuclear p27 expression or functional loss can promote uncontrolled proliferation, tumor progression, and treatment resistance. However, cytoplasmic p27 can acquire CDK-independent pro-oncogenic functions that promote cell motility, invasion, and aggressive tumor behavior.
Scientific Papers found: Click to Expand⟱
6901- FIS,    Fisetin induces G2/M phase arrest and caspase-mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC
- in-vivo, HNSCC, CAL33
TumCG↓, fisetin (25-75 µM for 24-48 h) dose-dependently inhibited growth and induced death in HNSCC Cal33 and UM-SCC-22B cells
TumCD↑,
selectivity↑, without showing any death in normal cells
TumCCA↑, Fisetin (25-50 µM) induced G2/M phase arrest via decrease in Cdc25C, CDK1, cyclin B1 expression, and an increase in p53(
CDC25↓,
CDK1↓,
CycB/CCNB1↓,
P53↑,
DNAdam↑, concentration-dependent increase in fisetin-induced DNA damage and apoptosis in HNSCC cells was authenticated by comet assay, gamma-H2A.X
Apoptosis↑,
γH2AX↑,
cl‑PARP↑, marked cleavage of PARP protein
other↝, Interestingly, fisetin-induced cell death occurred independently of p53 and reactive oxygen species production.
JNK↑, activation of JNK and inhibition of PI3K/Akt, ERK1/2, EGFR, and STAT-3 signaling were identified.
PI3K↓,
Akt↓,
ERK↓,
EGFR↓,
STAT3↓,
TumAuto↑, fisetin was also found to induce autophagy; nevertheless, autophagy attenuation exaggerated apoptosis.
Dose↝, Oral fisetin (50 mg/kg body weight) treatment to establish Cal33 xenograft in mice for 19 days showed 73% inhibition in tumor volume (p < 0.01) along with a decrease in Ki67-positive cells and an increase in cleaved caspase-3 level in tumors.
TumVol↓,
Ki-67↓,
cl‑Casp3↑,
P21↓, protein levels of p21Cip1 and P27Kip1 were also decreased by fisetin in tumors.
p27/CDKN1B↓,

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, NA
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, NA
*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.

3275- Lyco,    Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer
- Review, Var, NA
TumCCA↑, lycopene impedes the progress of the cell cycle from the G1 to the S phase, primarily by diminishing the cyclin D and cyclin E levels.
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓, causes a subsequent inactivation of CDK4 and CDK2 through a reduced phosphorylation of Rb
CDK4↓,
P21↑, lycopene elevates CDK inhibitor, p21, and p53 (tumor suppressor) levels
P53↑,
GSK‐3β↓, Finally, GSK3β, p21, p27, Bad, caspase 9, and p53 (via Mdm2) are inactivated
p27/CDKN1B↓,
Akt↓, lycopene inhibits AKT (protein kinase B) and mTOR
mTOR↓,
ROS↓, ability of lycopene to minimize ROS formation and mitigate oxidative stress
MMPs↓, lycopene may decrease the activity of metalloproteinases of the matrix and prevent SK-Hep1 cellular adhesion, invasion, and migration
TumCI↓,
TumCMig↓,
NF-kB↓, well-documented that lycopene inhibits NF-kB binding activity
*iNOS↓, They also claimed that the lycopene caused a decline in the LPS-induced protein and mRNA expression of iNOS,
*COX2/PTGS2↓, Lycopene can therefore decrease the gene expression of iNOS and COX-2 as a non-toxic agent via controlling pro-inflammatory genes
lipid-P↓, suppress gastric cancer by multimodal mechanisms of reduction in lipid peroxidation, elevation in the levels of antioxidants, and enhanced GSH
GSH↑,
NRF2↑, Reportedly, lycopene is known to “upregulate” this ARE system via Nrf2 in vitro (HepG2 and MCF-7 cells)

5795- MET,    Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes
- Review, AD, NA - Review, Park, NA - Review, Diabetic, NA
*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↓,

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
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/CDKN1B↓, figure 4
P21↓,
cycD1/CCND1↓,
Mcl-1↓,
survivin↓,

6456- TUR,    Ar-turmerone inhibits the proliferation and mobility of glioma by downregulating cathepsin B
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vitro, GBM, LN229
TumCP↓, Ar-turmerone reduced the proliferation rate and mobility of glioma cells in vitro and arrested cell division at G1/S phase
TumCCA↑, Ar-turmerone induced G1/S-phase arrest in glioma cells in vitro
CTSB↓, Ar-turmerone treatment reduced cathepsin B expression and inhibited the cleavage of its target protein P27 in glioma cells.
cl‑p27/CDKN1B↓,


Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   GSH↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,   IronCh∅, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

CDC25↓, 1,   MMP↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 5,   Apoptosis↑, 4,   Casp↑, 1,   cl‑Casp3↑, 1,   JNK↑, 1,   Mcl-1↓, 1,   p27/CDKN1B↓, 7,   cl‑p27/CDKN1B↓, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,   pRB↓, 3,   p‑pRB↓, 1,   tumCV↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 2,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↓, 4,   P21↑, 1,   TumCCA↑, 5,  

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

CTSB↓, 1,   Diff↑, 3,   ERK↓, 3,   GSK‐3β↓, 1,   mTOR↓, 2,   PI3K↓, 4,   RAS↓, 2,   STAT3↓, 1,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

Ki-67↓, 1,   MMP9↓, 1,   MMPs↓, 1,   PKCδ↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 4,   TumMeta↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 2,   Inflam↓, 3,   NF-kB↓, 4,   NK cell↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 3,   Dose↝, 1,   eff↑, 1,   selectivity↑, 3,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3,   AntiTum↓, 1,   chemoP↑, 1,   neuroP↑, 1,   QoL↑, 1,   Remission↑, 1,   RenoP↑, 1,   Risk↓, 1,   toxicity↓, 2,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 78

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Iron∅, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

Insulin↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

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

Cell Death(tgid=5) ⓘ

iNOS↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   Half-Life↝, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1,   cardioP↑, 2,   hepatoP↑, 1,   neuroP↑, 1,   toxicity↝, 1,  
Total Targets: 17

Scientific Paper Hit Count for: p27/CDKN1B, p27kip1
3 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
2 Inositol
1 Fisetin
1 Lycopene
1 Metformin
1 Resveratrol
1 Turmerones
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

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