P-gp/ABCB1 Cancer Research Results

P-gp/ABCB1, permeability-glycoprotein: Click to Expand ⟱
Source:
Type:
P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is a membrane protein that plays a crucial role in the transport of various substances across cellular membranes. It is part of the ATP-binding cassette (ABC) transporter family.
P-glycoprotein is often overexpressed in a variety of cancers, including breast cancer, lung cancer, leukemia, and ovarian cancer.

- The overexpression of P-glycoprotein (P-gp), is widely considered as an important reason for the MDR (multidrug resistance).

ABCB1 - ATP-Binding Cassette Subfamily B Member 1 / P-Glycoprotein

Abbreviation: ABCB1, P-gp, P-glycoprotein, MDR1

Type: ATP-dependent membrane efflux transporter / multidrug resistance protein

Function: ABCB1 encodes P-glycoprotein, an ATP-binding cassette transporter that exports a broad range of drugs, xenobiotics, lipids, and other substrates across cellular membranes. It is highly expressed in barrier tissues including the intestine, liver, kidney, placenta, and blood-brain barrier, where it limits tissue accumulation of potentially harmful compounds.

Cancer: ↑ Frequently overexpressed or functionally activated in drug-resistant tumors. Increased ABCB1 lowers intracellular concentrations of many anticancer agents by actively transporting them out of cancer cells, producing multidrug resistance and reducing chemotherapy effectiveness.

Alzheimer's Disease: ↓ Reduced ABCB1/P-glycoprotein expression or transport activity at the blood-brain barrier is associated with impaired amyloid-β clearance from the brain. Lower P-gp function correlates with increased cerebral Aβ accumulation and may contribute to Alzheimer's disease progression.
Scientific Papers found: Click to Expand⟱
6853- FBZ,    Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways
- vitro+vivo, Lung, A549 - in-vitro, Lung, H460
TumCD↑, exerts cytotoxicity to human cancer cells at micromolar concentrations.
P53↑, Simultaneously, it caused mitochondrial translocation of p53 and effectively inhibited glucose uptake, expression of GLUT transporters as well as hexokinase (HK II) - a key glycolytic enzyme that most cancer cells thrive on.
GlucoseCon↓,
GLUT4↓, FZ exposure reduced the expression of Glut-4 transporter as well as hexokinase (HK II), which may be linked to p53 activation and alteration of microtubule dynamics
HK2↓,
TumCG↓, It blocked the growth of human xenografts in nu/nu mice model when mice were fed with the drug orally.
P-gp/ABCB1∅, treated and untreated cells showed comparable levels of Rho123 accumulation affirming that FZ is not a substrate or inhibitor of P-gp.
TumCCA↑, FZ treatment results in early G2/M block accompanied by cell death
CycB/CCNB1↓, simultaneous decrease in cyclin B1 levels
eff↑, Tumour cell lines with wild-type p53 show enhanced sensitivity to FZ induced apoptosis
selectivity↑, Remarkably, FZ showed less toxicity towards primary epithelial cells cultured from rat lung tissue as compared to a lung cancer cell line
MMP↓, Correspondingly, mitochondrial membrane depolarization
lactateProd↓, FZ treatment also resulted in reduced lactate levels (Fig. 8c). Hence, FZ induced cell death appeared to be related to inhibition of glucose uptake.
eff↑, we conclude that FZ shows synergistic effect with DCA, 2DG and over a range of doses with taxol.
Dose↝, A549 cells and mice bearing tumours (2–3 mm) were fed with FZ (1 mg/mouse) orally every second day for 12 days
TumCG↓, FZ inhibits tumour cell growth in vivo by inducing apoptosis of tumour cells.


Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

GlucoseCon↓, 1,   HK2↓, 1,   lactateProd↓, 1,  

Cell Death(tgid=5) ⓘ

TumCD↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CycB/CCNB1↓, 1,   TumCCA↑, 1,  

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

TumCG↓, 2,  

Barriers & Transport(tgid=15) ⓘ

GLUT4↓, 1,   P-gp/ABCB1∅, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↑, 2,   selectivity↑, 1,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: P-gp/ABCB1, permeability-glycoprotein
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#:232  State#:%  Dir#:6
  wNotes=on  sortOrder:rid,rpid

 

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