Multidrug resistance (MDR) is a major obstacle of current chemotherapy. In this study, we investigated the effects ofpolyamines, acetylated polyamines and APAH, a polyamine deacetylase inhibitor, on LS180 cells and the derived MDR LS180 Ad-50 cells. L.ethal concentrations for 20% of the cells (LC20) for N8 -acetylspermidine (N8 - AcSPD) and SPD were 12.5 and 7 times greater for LS180 Ad-50 cells than for LS180 cells, respectively. However, there was no difference in LC20 levels for N1-AcSPD in LS180 and LS180 Ad-50 cells. Addition of 100 nM APAH to N8-AcSPD increased its LC20 to 17 foldgreater in MDR compared to non:·MDR cells. and resulted in increased cell growth at 5 μM N8-AcSPD. Furthermore, exposure to the LC20 concentrations of N8 -AcSPD for 48 hrs caused no significant change of intracellular Rhodamine (Rh) 123 concentrations. Adding 100 nM APAH to this N8 -AcSPD experiment led to a decrease of intracellular Rh123 concentration of 15-20% in both LS 180 and LS 180 Ad-50 cells. These Rh 123 concentrations further decreased in the presence of higher concentrations of APAH. Pretreatment of the cells with APAH did not affect these results. Kinetic studies suggest that APAH may be a non-competitive transport inhibitor of Rh123 transporter.
| Identifer | oai:union.ndltd.org:pacific.edu/oai:scholarlycommons.pacific.edu:uop_etds-1527 |
| Date | 01 January 1999 |
| Creators | Mao, Wenxian |
| Publisher | Scholarly Commons |
| Source Sets | University of the Pacific |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | University of the Pacific Theses and Dissertations |
Page generated in 0.0117 seconds