am-555s has been researched along with Pancreatic-Neoplasms* in 1 studies
1 other study(ies) available for am-555s and Pancreatic-Neoplasms
| Article | Year |
|---|---|
Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells.
In this study, we investigated the effect of a novel retinobenzoic acid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), on the growth of 4 human pancreatic-cancer cell lines; BxPC-3, MIAPaCa-2, CFPAC-1 and AsPC-1. TAC-101 significantly inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells in a time- and concentration-dependent manner, but not the proliferation of AsPC-1 cells. Furthermore, the anti-proliferative effects of TAC-101 on BxPC-3 and MIAPaCa-2 cells were stronger than those of all-trans retinoic acid. Flow-cytometric analyses indicated that treatment of BxPC-3 with TAC-101 strongly induces cell-cycle arrest at the G1 phase. The cell-cycle arrest induced by TAC-101 was accompanied by reduction of retinoblastoma-gene product (RB) phosphorylation and an increase of 2 cyclin-dependent kinase (CDK) inhibitors, p21(WAF1/Cip1) (p21) and p27Kip1 (p27). TAC-101 also caused a decrease in cyclin A and thymidylate synthase, which are E2F-regulated gene products. No changes were observed in the expression of cyclin D1, cyclin E on CDK2. In addition, Hoechst staining, gel electrophoresis and flow-cytometric analysis indicated that a marked reduction in the number of BxPC-3 cells with TAC-101 was related to the induction of apoptosis. Our results suggest that TAC-101 inhibits the growth of certain pancreatic-cancer cells by means of G1-phase cell-cycle arrest resulting from the reduction of RB phosphorylation and the up-regulation of p21 and p27 as well as the induction of apoptosis. TAC-101 may therefore be a useful agent for new therapeutic strategies focusing on inhibition of pancreatic-cancer-cell proliferation. Topics: Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Benzoates; Cell Cycle; Cell Division; Cell Nucleus; DNA Fragmentation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Kinetics; Pancreatic Neoplasms; Phosphorylation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Retinoic Acid; Retinoblastoma Protein; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tretinoin; Trimethylsilyl Compounds; Tumor Cells, Cultured | 1999 |