Molecular Mechanisms of Cell Death Induction by Nedaplatin in Human Tumor Cell Lines

概要

論文の詳細を見る
Nedaplatin is an antitumor agent which is used to treat neural, cervical, lung, esophagus, and bladder cancer. To elucidate the mechanism of cell death induced by nedaplatin, we compared tumor cell lines of different lineages : glioblastoma (T98G), an ectodermal cell line, and promyelocytic leukemic cells (HL-60), a mesenchymal cell line. Nedaplatin induced apoptotic cell death (characterized by internucleosomal DNA cleavage of 180 to 200 base pair multiples) in HL-60 cells, but induced necrotic changes without induction of DNA laddering pattern in T98G cells. To examine the effect of nedaplatin on protease activities that are believed to be involved in apoptosis, activities of interleukin 1β converting enzyme (ICE) family proteases, ICE protease and apopain, were examined using synthetic substrates in place of endogenous substrate poly (ADP-ribose) polymerase. Nedaplatin activated apopain only in HL-60 cells but failed to activate ICE protease in either cell line. Immunoblot analysis with anti-bcl-2 antibody demonstrated that the 24-kDa protein was only expressed in the cytosol of nedaplatin-treated T98G cells. The present study demonstrates that nedaplatin triggers different signal transduction pathways for cell death induction among cells of different origin.
昭和大学・昭和医学会の論文