G(1) Phase growth arrest and induction of p21(Waf1/Cip1/Sdi1) in IB3-1 cells treated with 4-sodium phenylbutyrate.
|
| Abstract |
4-Sodium phenylbutyrate (4-PBA) has been used for many years in the treatment of urea cycle defects and has recently been studied as a chemotherapeutic agent for certain malignancies. 4-PBA has been shown to cause growth arrest, cellular differentiation, and apoptosis in certain malignant cells. Recently, it was shown that IB3-1 cells (a cystic fibrosis cell line, Delta508/W128X) treated with 4-PBA demonstrated a partial correction of the cystic fibrosis chloride channel defect. We were interested in evaluating the effect of 4-PBA on cell growth and cell cycle regulation in IB3-1 cells treated with 2 to 10 mM concentrations. We found that cells treated with 2 mM concentrations of 4-PBA for 96 h underwent a significant decrease in cell growth (P <.007). Using flow cytometry, we were able to demonstrate that growth arrest occurred at the G(1) phase of the cell cycle. This was detected as early as 24 h in IB3-1 cells treated with 5 mM 4-PBA (P <.03). Furthermore, the percentage of IB3-1 cells with less than a 2N DNA content increased with higher concentrations of 4-PBA, although this was not associated with an increase in apoptosis. Finally, p21(Waf1/Cip1/Sdi1) protein levels were induced in IB3-1 cells receiving 2 and 5 mM concentrations of 4-PBA as early as 24 h of exposure, suggesting that G(1) phase growth arrest in IB3-1 cells treated with 4-PBA is regulated through the p21(Waf1/Cip1/Sdi1) pathway.
|
|---|---|
| Authors | S A McGrath-Morrow, J L Stahl |
| Journal | The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 294 Issue 3 Pg. 941-7 (Sep 2000) ISSN: 0022-3565 [Print] United States |
| PMID | 10945844 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!