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Comparison of the effect of acetylated polyamines and N⁸-acetylspermidine deacetylase inhibitor, APAH, on LS180 and multidrug resistant cells

Author

Wenxian Mao, University of the Pacific

Date of Award

1999

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Pharmacy

First Advisor

James W. Blankenship

First Committee Member

John Livesey

Second Committee Member

Tim Smith

Third Committee Member

Celestia Pryor

Abstract

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.

Pages

79

Recommended Citation

Mao, Wenxian. (1999). Comparison of the effect of acetylated polyamines and N⁸-acetylspermidine deacetylase inhibitor, APAH, on LS180 and multidrug resistant cells. University of the Pacific, Thesis - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/528