Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2)FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line
机构：[1]Department of Radiology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan[2]Faculty of Health Sciences, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan[3]Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China河北医科大学第四医院[4]Graduate Center for Toxicology, the University of Kentucky, 340 Health Science Research Building, Lexington, KY 40536-0305, USA
We previously developed a new microscopic observation system that enables time-lapse quantitative analysis of apoptosis and necrosis. With this system we quantitatively analyzed adriamycin (ADR)-induced cell death using manganese superoxide dismutase (MnSOD)- and wild-type p53-gene transfectants on SaOS(2) a p53-deficient human osteosarcoma cell line. A highly MnSOD-over-expressing cell line, SaOS(2)FM(H), acquired ADR-tolerance compared to the parent cell line SaOS(2). The ADR-tolerance of SaOS(2)FM(H) diminished by L-buthionine-[S,R]-sulfoximine (BSO), which did not change ADR-sensitivity of SaOS, to the similar ADR-sensitivity of SaOS(2). A wild-type p53-expressing cell line, SaOS(2)wtp53, significantly increased in ADR-sensitivity compared to SaOS, This ADR-sensitivity of SaOS,wtp53 was enhanced by BSO. When isosorbide 5-mono-nitrate was combined with BSO, isosorbide 5-mononitrate increased ADR sensitivity of a moderately MnSOD-over-expressing cell line. SaOS,FM(L), decreased that of SaOS, FM(H), and did not change those of SaOS, and SaOS2wtp53 compared to BSO alone. Time-lapse microscopic observations during ADR treatment for 24 h indicated that the most cells of each cell line underwent apoptosis, and a few cells (less than 11%) died by necrosis. When cells were treated with isoconcentration of ADR, apoptosis of SaOS,FM(H) was less than that of SaOS(2). BSO, which did not change ADR-sensitivity of SaOS(2), increased appearance rate of ADR-induced apoptosis, but not necrosis of MnSOD-over-expressing cell lines. When iso-survival dose of ADR, which reduced surviving fraction to 0.01, was given for each cell line, no difference was observed in appearance of either apoptosis or necrosis between SaOS(2) and MnSOD-overexpressing cell lines. On the other hands, appearance of both apoptosis and the following secondary necrosis of SaOS(2) wtp53 was significantly accelerated compared to those of SaOS(2). These findings indicate that hydrogen peroxide overload on p53-independent pathway due to MnSOD overexpression plus BSO might increase the apoptosis frequency without acceleration of apoptotic process of each cell, resulting in negating ADR-tolerance of MnSOD-overexpressing cell lines.
基金：
Grant-in-Aid for
International Scientific Research [Joint Research (08044290)]
and a Grant-in-Aid for Scientific Research [B (10470196)
and B (14370278)] and Exploratory Research [138770141 and
156592801] from the Ministry of Education, Science, Sports
and Culture of Japan.
第一作者机构：[1]Department of Radiology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
通讯作者：
通讯机构：[1]Department of Radiology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan[*1]Department of Radiology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
推荐引用方式(GB/T 7714)：
Wang YD,Kuroda M,Gao XS,et al.Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2)FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line[J].INTERNATIONAL JOURNAL OF ONCOLOGY.2005,26(5):1291-1300.doi:10.3892/ijo.26.5.1291.
APA：
Wang, YD,Kuroda, M,Gao, XS,Asaumi, J,Shibuya, K...&Kanazawa, S.(2005).Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2)FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line.INTERNATIONAL JOURNAL OF ONCOLOGY,26,(5)
MLA：
Wang, YD,et al."Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2)FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line".INTERNATIONAL JOURNAL OF ONCOLOGY 26..5(2005):1291-1300
