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An association of Bcl‐2 phosphorylation and Bax localization with their functions after hyperthermia and paclitaxel treatment
Author(s) -
Salaheldin Alaaeldin,
Inoue Shoichi,
Tsukamoto Shigeki,
Aoi Hiromi,
Tsuda Masumi
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10782
Subject(s) - paclitaxel , apoptosis , hyperthermia , phosphorylation , biology , kinase , cytoplasm , intracellular , cancer research , mitochondrion , microbiology and biotechnology , biochemistry , chemotherapy , genetics , paleontology
Apoptosis is induced by many kinds of therapy‐related inducers, such as hyperthermia and chemotherapeutic agents. However, differences in apoptotic pathways between these inducers remain unclear, although knowing the differences is important to map out a therapeutic strategy. Therefore, we focused on the localization and phosphorylation of Bcl‐2 and Bax, key mediators of the apoptotic pathway, after hyperthermia and paclitaxel treatment of PC‐10 squamous cell carcinoma cells that excessively expressed Bcl‐2 and Bax in the cytoplasm. Paclitaxel treatment markedly induced qualitative changes in Bcl‐2, whereas hyperthermia did only quantitative changes in Bax. The levels of Bax increased gradually with the duration of hyperthermia, whereas Bcl‐2 levels slightly decreased. On the other hand, paclitaxel treatment induced dose‐ and time‐dependent phosphorylation of Bcl‐2. Interestingly, phosphorylated Bcl‐2 was observed in the specific subcellular sites, mitochondria‐ and lysosome‐rich fractions. Both treatments disturbed the heterodimerization of Bax with Bcl‐2. Hyperthermia, but not paclitaxel treatment, induced a gradual Bax translocation from the cytoplasm to the nucleus. Although both treatments induced a prominent cell cycle disturbance in the G2M phase, paclitaxel treatment induced typical apoptosis, and hyperthermia hardly induced apoptosis. Our results suggest that the subcellular redistribution of Bax and the phosphorylation of Bcl‐2 depend on the type of apoptosis inducers, such as hyperthermia and paclitaxel, and Bcl‐2 has a central role in the decision of apoptotic outcome. Our data may afford new insights in apoptosis from the aspect of an association of Bcl‐2 phosphorylation with intracellular Bax localization. © 2002 Wiley‐Liss, Inc.