Timed, sequential administration of paclitaxel improves its cytotoxic effectiveness in a cell culture model.
Paclitaxel (taxol) is a chemotherapeutic agent frequently used in combination with other anti-neoplastic drugs. It is most effective during the M phase of the cell-cycle and tends to cause synchronization in malignant cells lines. In this study, we investigated whether timed, sequential treatment based on the cell-cycle characteristics could be exploited to enhance the cytotoxic effect of paclitaxel. We characterized the cell-cycle properties of a rapidly multiplying cell line (Sp2, mouse myeloma cells) by propidium-iodide DNA staining such as the lengths of various cell cycle phases and population duplication time. Based on this we designed a paclitaxel treatment protocol that comprised a primary and a secondary, timed treatment. We found that the first paclitaxel treatment synchronized the cells at the G2/M phase but releasing the block by stopping the treatment allowed a large number of cells to enter the next cell-cycle by a synchronized manner. The second treatment was most effective during the time when these cells approached the next G2/M phase and was least effective when it occurred after the peak time of this next G2/M phase. Moreover, we found that after mixing Sp2 cells with another, significantly slower multiplying cell type (Jurkat human T-cell leukemia) at an initial ratio of 1:1, the ratio of the two different cell types could be influenced by timed sequential paclitaxel treatment at will. Our results demonstrate that knowledge of the cell-cycle parameters of a specific malignant cell type could improve the effectivity of the chemotherapy. Implementing timed chemotherapeutic treatments could increase the cytotoxicity on the malignant cells but also decrease the side-effects since other, non-malignant cell types will have different cell-cycle characteristic and be out of synch during the treatment.
a Department of Laboratory Medicine , University of Pécs , Pécs , Hungary.
Viktória
V
Fisi
a Department of Laboratory Medicine , University of Pécs , Pécs , Hungary.
Emese
E
Kátai
b Department of Radiology , University of Pécs , Pécs , Hungary.
Péter
P
Bogner
a Department of Laboratory Medicine , University of Pécs , Pécs , Hungary.
Attila
A
Miseta
a Department of Laboratory Medicine , University of Pécs , Pécs , Hungary.
Tamás
T
Nagy
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008954:Models, Biological; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D013997:Time Factors
D017239:Paclitaxel
cell cycle; cell synchronization; chemotherapy; mitotic arrest; paclitaxel