Department of Genetic Engineering, Chongju University, Chongju, Korea.
ABSTRACT
PURPOSE: Apoptosis is a form of cell death characterized by specific morphological changes in the dying cell including contraction of cytoplasm, chromatin condensation, and cellular fragmentation into membrane-bound bodies. A common biological marker of apoptosis is the degradation of nuclear DNA resulting in a ladder of nucleosome-sized DNA fragments when resolved by electrophoresis. The potential therapeutic implications of simultaneous activation of apoptosis in androgen-dependent and androgen-independent prostatic cells are clearly very important in the development of cancer treatment modalities for advanced prostate cancer. The efficacy of chemotherapeutic agents correlates with their ability to induce apoptosis, Therefore, quantification of experimentally induced apoptosis in cancer cell lines is likely to be a predictor of the outcome of treatment. The main objective of this study was to examine the induction of apoptosis as a new strategy for cancer therapy by cis-diamminedichloroplatinum (CDDP) or 12-0-tetradecanoyl phorbol 13-acetate (TPA) in human prostate (androgen-dependent LNCaP and androgen-independent DU-145), and breast cancer cells (MCF-7).
MATERIALS AND METHODS: DNA gel electrophoresis, flow cytometry and transmission electron microscopy for morphological analysis were used to further characterize drug response in human prostate and breast cancer cells.
RESULTS: Treatment of the LNCaP and DU-145 cells with CDDP or TPA resulted in dose-dependent growth inhibition and accumulation of cells in Ao (apoptotic region), and caused significant degradation of the genomic DNA into intemucleosomal-sized DNA fragments, indicating apoptosis.
In contrast, MCF-7 cells showed little or no DNA fragmentation.
CONCLUSION: These studies suggest that a differential susceptibility to apoptosis and chemosensitivity may be related to the efficacy of chemotherapeutic .agents. CDDP and TPA may have clinical implication in the treatment of prostate cancer. In particular, cytotoxic effects of TPA may well lead to new possibilities for improved strategy.
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