2003 Fiscal Year Final Research Report Summary
Development of As203-besed new chemotherapy for advanced prostate cancer
| Project/Area Number |
14370514
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | KAGAWA UNIVERSITY(FACULTY OF MEDICINE) |
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Principal Investigator |
KAKEHI Yoshiyuki Kagawa University(Faculty of Medicine), Urology, Professor, 医学部, 教授 (20214273)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIZUKA Akira Kyoto University, Graduate School of Biostudies, Professor, 大学院・生命科学研究科, 教授 (80204329)
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| Project Period (FY) |
2002 – 2003
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| Keywords | arsenic trioxide / apoptosis / prostate cancer / renal cancer / buthionine sulfoximine / reactive oxveren species |
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| Research Abstract |
Arsenic trioxide (As203) induces clinical remission in acute promyelocytic leukemic patients and apoptosis in various tumor cells in vitro and in vivo. The purpose of this study is to develop As203-based new chemotherapy for hormone refractory prostate cancer and advanced renal cancer. Major findings of our experiments are following ; 1)Higher concentration (10-100uM) of As203 induced apoptosis and lower concentration 0.1? 10uM) of As203 resulted in inhibition of cell growth in androgen insensitive prostate cancer PC3 and Du145 cells. 2)As203 activated p38, JNK, caspase-3 in a dose-dependent manner. 3)An anti-oxidant N-acetyl-cysteine inhibited the apoptosis induced by As203 through suppressing p38, JNK, and caspase-3 activity and ROS production. Based on the results described above, we investigated whether lower concentration of As203 could induce apoptosis by suppressing radical scavenging system. As a consequence, combination of lower concentration of As203 with L-buthionine sulfoximine (BSD) successfully induced apoptosis in prostate, renal, breast, and lung cancers in vitro but did not in normal cells (Cell Death Differ 2004).
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