Defective Apoptotic Signal Transduction Pathway Downstream of Caspase-3 in Human B-Lymphoma Cells: A Novel Mechanism of Nuclear Apoptosis Resistance

Author:

Kawabata Yoshinari1,Hirokawa Makoto1,Kitabayashi Atsushi1,Horiuchi Takahiro1,Kuroki Jun1,Miura Akira B.1

Affiliation:

1. From the Department of Internal Medicine III, Akita University School of Medicine, Akita, Japan.

Abstract

Mitochondria play a central role in controlling apoptosis, and activation of the caspase cascade appears to be crucial event during the apoptotic process. Human B lymphoma Raji cells are resistant to nuclear apoptosis induced by various stimuli. Using this cell line, we have asked whether reduction of the mitochondrial transmembrane potential and activation of caspase-3 are sufficient to induce DNA fragmentation during the apoptotic process. After stimulation with cell-permeable C2-ceramide or mitochondrial permeability transition (PT) inducers, not only apoptosis-sensitive cell lines (HL-60, Jurkat, and Daudi cells), but also Raji cells showed reduction of the mitochondrial transmembrane potential (▵ψm), activation of caspase-3, and loss of clonogenic potential. However, Raji cells did not show detectable levels of nuclear apoptosis (DNA degradation). In a cell-free system, cell lysates from tetra-butylhydroperoxide (t-BHP)–treated HL-60 cells induced DNA degradation of Raji nuclei, whereas cell lysates from t-BHP–treated Raji cells failed to induce DNA degradation in either apoptosis-sensitive cell lines or apoptosis-resistant Raji cells. Cleavage of DFF-45, which is a downstream target molecule for caspase-3, was observed in Raji cells as well as in apoptosis-sensitive Daudi cells. These results indicate that there is a defective apoptotic pathway in the cytoplasm downstream of caspase-3 in Raji cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference41 articles.

1. Apoptosis death factor.;Nagata;Cell,1997

2. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs.;Kaufmann;Cancer Res,1989

3. Induction of internucleosomal DNA fragmentation in human myeloid leukemia cells by 1-β-D-arabinofuranosylcytosine.;Gunji;Cancer Res,1991

4. Effects of cisplatin on the induction of apoptosis in proliferating hepatoma cells and nonproliferating immature thymocytes.;Evans;Cancer Res,1993

5. Drug-induced apoptosis is not necessary dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line.;Borner;Cancer Res,1995

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