| Project/Area Number |
11671187
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Jikei University school Medicine |
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Principal Investigator |
KUBO Hirotaka Jikei University school of Medicine Secand Depertment of Surgery Assi. Professer, 外科学第2教室, 助教授 (70119791)
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| Co-Investigator(Kenkyū-buntansha) |
KANEDA Toshiaki Jikei University school of Medicine Secand Depertment of Surgery Assistant, 外科学第2教室, 助手 (40266606)
KANOU Kazutaka Univeristy of Tokyo Physiplogical Cheistry and Nutrition Assistant, 大学院・医学系研究科・代謝生理化学, 助手 (70111507)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Breast cancer / Hormon therapy / Estrogen / Apotpsis / Antiestorogen / Tamoxifen / DNA damege / Mitochondrial respiration / Caspase-3 / エストゴゲン受容体 |
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| Research Abstract |
(The aim of the project)
The aim of this project is to investgate the appropriate anti-estrogen drug (s) or the combination of anti-estrogen and other drugs for the treatment of breast cancer case using malignant cells in surgical removal. We found that frequently used anti-estrogen drug tamoxifen induced apoptosis in cultured human monocytic leukemia cell line U937 and other cell lines. The experiments were done using human monocytic leukemia cell line U937 as a model. We found several anti-estrogen and related drugs induced apoptosis.
(Results )
1 Tamoxifen-induced apoptotic cell death in the promonocytic cells U937 during 4 h culture period. Cell internucleosomal DNA fragmentation, which is considered to be an characteristic event in apoptosis, was detected within 3 h after the treatment with 50 microM of tamoxifen, incresed with longer exposure times.
2 Tamoxifen-induced caspase-3 activity
The activity of caspase-3 increased with raising the tamoxifen concentration. In the time course experiment with tamoxifen at the concentration of 50 * M up to 4 h. caspase-3 activity had detected within 30 min, and reached the maximal activity at 3 h, about 8-10 times higher than that of control, In contrast to caspase-3.
3. Using isolated mitochondria, we showed that tamoxifen inhibited mitochondrial respiratory chain complexes II, III, IV.
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