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Over‐expression of APAF‐1 and caspase‐9 augments radiation‐induced apoptosis in U‐373MG glioma cells
Author(s) -
Shinoura Nobusada,
Sakurai Shinya,
Asai Akio,
Kirino Takaaki,
Hamada Hirofumi
Publication year - 2001
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.1327
Subject(s) - apoptosis , radioresistance , caspase 9 , caspase 3 , biology , microbiology and biotechnology , uvb induced apoptosis , cancer research , cancer cell , glioma , caspase , programmed cell death , cell culture , cancer , genetics
The p53 tumor‐suppressor gene plays a critical role in radiation‐induced apoptosis. Several genes, including Bax and Fas, are involved in p53 ‐mediated apoptosis, and their over‐expression enhances the degree of radiation‐induced apoptosis. Apaf‐1 and caspase‐9 have been reported to be downstream components of p53 ‐mediated apoptosis, suggesting that these genes play a role in radiation‐induced apoptosis. In this study, we transduced U‐373MG cells harboring mutant p53 with the Apaf‐1 and/or caspase‐9 genes via adenoviral (Adv) vectors concomitant with X‐ray irradiation and evaluated the degree of apoptosis. The percentage of apoptotic cells in U‐373MG cells co‐infected with the Adv for Apaf‐1 (Adv‐APAF‐1) and that for caspase‐9 (Adv‐Casp9) and treated with irradiation (24%) was much higher than that in cells co‐infected with Adv‐APAF‐1 and Adv‐Casp9 and not treated with irradiation (0.86%) and that in cells infected with either Adv‐APAF‐1 or Adv‐Casp9 and treated with irradiation (2.0% or 2.6%, respectively). The apoptosis induced by co‐transduction of Apaf‐1 and caspase‐9 and irradiation was repressed in cells that were co‐infected with the Adv for Bcl‐X L but not in cells co‐infected with the Adv for Bcl‐2. These results indicate that Apaf‐1 and caspase‐9 play a role in radiation‐induced apoptosis in cancer cells harboring mutant p53. Bcl‐X L may be critically involved in the radioresistance of cancer cells by repressing Apaf‐1 – and caspase‐9 –mediated apoptosis. Expression of Apaf‐1 and caspase‐9 in tumors may be an important determinant of the therapeutic effect of irradiation in cancer treatment. © 2001 Wiley‐Liss, Inc.