2012 Fiscal Year Final Research Report
Development of new therapy targeting prostate cancer through DNA Damage Response under oxidative stress
| Project/Area Number |
22591778
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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 |
Urology
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | 前立腺癌 / 酸化ストレス / アンドロゲン |
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| Research Abstract |
Sustained chronic inflammation and oxidative stress in the prostate promote prostate carcinogenesis. The process of oncogenic transformation leads to enhanced DNA damage and activates the checkpoint network that functions as an inducible barrier against cancer progression. Here, we analyzed the effects of testosterone on the DNA damage response in prostate cancer cells to assess whether testosterone functions a barrier to cancer progression under the oxidative stress. H_2O_2 induced apoptosis and phosphorylation of ATM, Chk2, and H2AX in prostate cancer cells. Androgen treatments increased H_2O_2-induced activation of the DNA damage response and PARP cleavage, but not when the H_2O_2-treated cells were also treated with the anti-androgen flutamide. In this study, we also examined the biological effects of soy isoflavones and curcumin through the DNA damage response in prostate cancer cells. In conclusions, DNA damage response plays important roles in the maintenance of the cell homeostasis in response to oxidative stress during aging. Our results indicate that androgen signaling have tumor suppressive effects in prostate carcinogenesis through DNA damage response pathways under oxidative stress. In addition, our results may indicate that isoflavones and curcumin can modulate serum PSA levels and presumably suppress prostate carcinogenesis through the suppression of androgen receptor expression and the activation of DNA damage signaling pathways.
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[Journal Article] Testosterone promotes DNA damage response under oxidative stress in prostate cancer cell lines2012
Author(s)
Ide,H., Yu, J., Lu, Y., China, T., Kumamoto, T., Koseki, T., Muto, S., Horie, S
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Journal Title
Prostate
Volume: 72
Pages: 1407-11
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[Journal Article] Clinical possibility of CRH test in Subclinical Cushing's syndrome to predict the cortisol replacement after adrenorectomy2012
Author(s)
Inoue, S., Ide,H., Kurihara, K., Koseki, T., Yu, J., China, T., Saito, K., Isotani, S., Muto, S., Horie, S
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Journal Title
Korean J Urol
Volume: 53
Pages: 414-8
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[Journal Article] Clinical and safety profiles of bipolar transurethral vaporization of the prostate in saline: a preliminary report2012
Author(s)
Isotani,S., Muto, S., Yu, J., Nagae, M., China, T., Koseki, T., Kumamoto, T., Tokiwa, S., Yoshii, T., Saito, K., Yamaguchi, R., Ide, H., Horie, S
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Journal Title
Asian J Endosc Surg
Volume: 5
Pages: 21-4
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[Journal Article] Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP2011
Author(s)
Ide,H., Yu, J., Lu, Y., China, T., Kumamoto, T., Koseki, T., Muto, S., Horie, S
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Journal Title
Cancer Sci
Volume: 102
Pages: 468-71
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[Presentation] 根治的前立腺全摘除施行例における血清 LH, FSH 値の検討2012
Author(s)
井手久満, 坂巻顕太郎, 寺戸雄一, 知名俊幸, 小関達郎, 常盤紫野, 吉井隆, 斉藤恵介,磯谷周治, 久末伸一, 山口雷蔵, 井手久満, 堀江重郎
Organizer
第100回日本泌尿器科学会総会
Place of Presentation
東京
Year and Date
20120000
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[Presentation] 根治的前立腺全摘除術施行例における血清 LH、FSH 値の臨床的検討2011
Author(s)
井手久満, 寺戸雄一, 坂巻顕太郎, 知名俊幸, 小関達郎, 常盤紫野, 吉井隆, 斎藤恵介, 磯谷周治, 久末伸一, 山口雷藏, 武藤智, 堀江重郎
Organizer
第49回日本癌治療学会学術集会
Place of Presentation
名古屋
Year and Date
20110000
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[Presentation] 根治的前立腺全摘除術施行例における血清 LH、FSH 値の臨床的検討2011
Author(s)
井手久満, 吉井隆, 坂巻顕太郎, 寺戸雄一, 知名俊幸, 小関達郎, 熊本友香, 常盤紫野, 斎藤恵介, 磯谷周治, 山口雷藏, 武藤智, 堀江重郎
Organizer
第99回日本泌尿器科学会総会
Place of Presentation
名古屋
Year and Date
20110000
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[Presentation] クルクミンによる前立腺癌細胞増殖ならびに浸潤抑制機構の解明2011
Author(s)
堀江重郎, 陸彦, 于浄松, 知名俊幸, 小関達郎, 熊本友香, 斎藤恵介, 磯谷周治, 山口雷藏, 井手久満, 武藤智
Organizer
第99回日本泌尿器科学会総会
Place of Presentation
名古屋
Year and Date
20110000
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