University of the Pacific
Comparison of the effect of acetylated polyamines and N⁸-acetylspermidine deacetylase inhibitor, APAH, on LS180 and multidrug resistant cells
Abstract
dc:description.abstract<p>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 (LC<sub>20</sub>) for N<sup>8</sup> -acetylspermidine (N<sup>8</sup> - 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 LC<sub>20</sub> levels for N<sup>1</sup>-AcSPD in LS180 and LS180 Ad-50 cells. Addition of 100 nM APAH to N<sup>8</sup>-AcSPD increased its LC<sub>20</sub> to 17 foldgreater in MDR compared to non:·MDR cells. and resulted in increased cell growth at 5 μM N<sup>8</sup>-AcSPD. Furthermore, exposure to the LC20 concentrations of N<sup>8</sup> -AcSPD for 48 hrs caused no significant change of intracellular Rhodamine (Rh) 123 concentrations. Adding 100 nM APAH to this N<sup>8</sup> -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.</p>
Degree
thesis:*- Name thesis:degree_name
- Master of Science (M.S.)
- Level thesis:degree_level
- Thesis - Pacific Access Restricted
- Discipline thesis:degree_discipline
- Pharmacy
- Year dc:date.available
- 1999
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Mao, Wenxian
- Contributors dc:contributor
-
- James W. Blankenship
Subjects
dc:subject × 7Rights
dc:rightsIdentifiers
dc:identifier.*- Repository record dc:identifier
- https://scholarlycommons.pacific.edu/uop_etds/528
- OAI identifier oai:identifier
- oai:scholarlycommons.pacific.edu:uop_etds-1527