Phenylbutyrate / CHOP Cancer Research Results

PB, Phenylbutyrate: Click to Expand ⟱
Features:
Used to treat urea cycle disorders
Sodium phenylbutyrate helps remove ammonia from the body.
-Phenyl-butyrate (PB)4 is an aromatic fatty acid that is converted in vivo to phenylacetate (PA) by β-oxidation in liver and kidney mitochondria.
-In human body, phenylbutyrate is oxidized to phenylacetate, which is in turn conjugated with glutamine and eliminated in urine as phenylacetylglutamine, thereby mediating elimination of waste nitrogen
-Phenylbutyrate is one of the first drugs encountered in cancer therapy as a histone deacetylase inhibitor (HDACI) (relatively weak compared to vorinostat (SAHA), romidepsin, etc.).
-Butyric acid is one of the short-chain fatty acids produced by the gut microbiota through the fermentation of dietary fiber. Butyrate is primarily recognized for its beneficial effects in the colon and is tightly linked to gut health.
-Phenylbutyrate is a derivative of butyrate that has been chemically modified by the addition of a phenyl group. This structural change increases its lipophilicity (fat solubility) and alters its metabolic fate and biological activity. This allows it to be used as a systemic drug, in contrast to the locally produced butyrate in the gut, which is rapidly metabolized by colonocytes

Pathways:
-Histone deacetylase (HDAC) inhibitor
-ER stress inhibitor (at least in normal cell)
-Can act as a chemical chaperone, helping to reduce ER stress by facilitating proper protein folding.
-Modulation of NF-κB Signaling
-Changes in pathways such as PI3K/Akt/mTOR and MAPK.
-Some preclinical investigations have reported that treatment with phenylbutyrate leads to mitochondrial dysfunction and endoplasmic reticulum (ER) stress, both of which can result in an increase of ROS within cancer cells.

Note: Sodium butyrate (NaBu) vs Sodium phenylbutyrate
-Sodium butyrate is primarily a research tool with limited clinical application, whereas phenylbutyrate is used clinically
-Phenylbutyrate typically exhibits improved pharmacokinetics and is more amenable to systemic use compared to sodium butyrate.
-Both compounds act as HDAC inhibitors, phenylbutyrate additionally modulates ER stress and mitochondrial function, leading to potentially greater ROS production in certain cancer cells.

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Rank Pathway / Axis Cancer Context Normal Tissue Context TSF Primary Effect Notes
1 Histone Deacetylase (HDAC) inhibition Histone acetylation ↑; p21 ↑; differentiation ↑; proliferation ↓ Gene-expression modulation R, G Epigenetic reprogramming Core anticancer mechanism; early-generation, relatively weak HDAC inhibitor.
2 Cell-cycle arrest G1 arrest ↑; Cyclin D1 ↓ (reported) G Cytostasis Common downstream effect of HDAC inhibition.
3 Apoptosis Caspase activation ↑ (reported; model-dependent) G Cell death execution Often secondary to transcriptional changes and stress modulation.
4 ER stress / Chemical chaperone activity Context-dependent: ER stress ↑ or ↓ ER stress ↓ (protein misfolding disorders) R, G Protein-folding modulation Acts as chemical chaperone; effect depends on cell type and dose.
5 NF-κB signaling NF-κB modulation (reported) Inflammatory tone modulation R, G Transcriptional regulation Likely secondary to epigenetic changes.
6 PI3K → AKT / MAPK pathways Survival pathway modulation (reported; model-dependent) R, G Growth signaling modulation Downstream transcriptional effects rather than primary kinase inhibition.
7 Mitochondrial stress / ROS ROS modulation (context-dependent) P, R, G Metabolic adaptation Not a primary ROS-inducing agent; effects vary by tumor model.
8 Urea-cycle nitrogen scavenging (approved indication) Ammonia elimination ↑ (phenylacetylglutamine formation) Clinical metabolic role Primary approved medical use.


CHOP, GADD153: Click to Expand ⟱
Source:
Type: Protein
GADD153 and CHOP (C/EBP-homologous protein) refer to the same protein. GADD153 stands for "Growth Arrest and DNA Damage-inducible protein 153," while CHOP stands for "C/EBP Homologous Protein."
DDIT3 (DNA Damage Inducible Transcript 3), also known as CHOP (C/EBP Homologous Protein), is a transcription factor that plays a significant role in the cellular response to stress, particularly in the context of the unfolded protein response (UPR) and apoptosis.

CHOP is an important component of the endoplasmic reticulum (ER) stress response. Research has shown that knockdown of CHOP not only enhances tunicamycin-induced autophagy, but also significantly attenuates ER stress-induced apoptosis in human colon cancer cells.
GADD153, also known as CHOP (C/EBP homologous protein), is a transcription factor that plays a significant role in cellular stress responses, particularly in the context of the endoplasmic reticulum (ER) stress response. It is part of the unfolded protein response (UPR), which is activated when there is an accumulation of misfolded proteins in the ER.


Scientific Papers found: Click to Expand⟱
2065- PB,  TMZ,    Inhibition of Mitochondria- and Endoplasmic Reticulum Stress-Mediated Autophagy Augments Temozolomide-Induced Apoptosis in Glioma Cells
- in-vitro, GBM, NA
eff↑, ROS↑, MMP↓, ER Stress↑, CHOP↑, GRP78/BiP↑, pro‑Casp12↓, eff↝, Ca+2↝,
2076- PB,    Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29
TumCP↓, TumAuto↑, Apoptosis↑, ER Stress↑, BID↑, CHOP↑, PDI↑, IRE1↓, LC3‑Ⅱ/LC3‑Ⅰ↑, LC3B↑, Beclin-1↑, other↝, other↝,
2028- PB,    Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms
- Review, Var, NA
HDAC↓, TumCCA↑, P21↑, Dose↝, Telomerase↓, IGFBP3↑, p‑p38↑, JNK↑, ERK↑, BAX↑, Casp3↑, Bcl-2↓, Cyt‑c↝, FAK↓, survivin↓, VEGF↓, angioG↓, DNArepair↓, TumMeta↓, HSP27↑, ASK1↑, ROS↑, eff↑, ER Stress↓, GRP78/BiP↓, CHOP↑, AR↓, other?,
2041- PB,    The Effect of Glucose Concentration and Sodium Phenylbutyrate Treatment on Mitochondrial Bioenergetics and ER Stress in 3T3-L1 Adipocytes
- in-vitro, Nor, 3T3
*mitResp↓, *ER Stress↓, MMP↓, GlucoseCon↓, OCR↓, CHOP↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ROS↑, 2,  

Mitochondria & Bioenergetics

MMP↓, 2,   OCR↓, 1,  

Core Metabolism/Glycolysis

GlucoseCon↓, 1,  

Cell Death

Apoptosis↑, 1,   ASK1↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   BID↑, 1,   pro‑Casp12↓, 1,   Casp3↑, 1,   Cyt‑c↝, 1,   JNK↑, 1,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Transcription & Epigenetics

other?, 1,   other↝, 2,  

Protein Folding & ER Stress

CHOP↑, 4,   ER Stress↓, 1,   ER Stress↑, 2,   GRP78/BiP↓, 1,   GRP78/BiP↑, 1,   HSP27↑, 1,   IRE1↓, 1,  

Autophagy & Lysosomes

Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair

DNArepair↓, 1,  

Cell Cycle & Senescence

P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

ERK↑, 1,   HDAC↓, 1,   IGFBP3↑, 1,  

Migration

Ca+2↝, 1,   FAK↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,   PDI↑, 1,   VEGF↓, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

Dose↝, 1,   eff↑, 2,   eff↝, 1,  

Clinical Biomarkers

AR↓, 1,  
Total Targets: 47

Pathway results for Effect on Normal Cells:


Mitochondria & Bioenergetics

mitResp↓, 1,  

Protein Folding & ER Stress

ER Stress↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: CHOP, GADD153
4 Phenylbutyrate
1 temozolomide
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#:15  Target#:490  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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