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Title: A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor.
Authors: Xing, Nai-Dong
Ding, Sen-Tai
Saito, Ryoichi
Nishizawa, Koji
Kobayashi, Takashi  kyouindb  KAKEN_id
Inoue, Takahiro  kyouindb  KAKEN_id
Oishi, Shinya  kyouindb  KAKEN_id
Fujii, Nobutaka  KAKEN_id
Lv, Jia-Jv
Ogawa, Osamu  kyouindb  KAKEN_id
Nishiyama, Hiroyuki
Author's alias: 小川, 修
西山, 博之
Keywords: Eg5 protein
prostate cancer
S-(methoxytrityl)-L-cysteine
Issue Date: Mar-2011
Publisher: Nature Publishing Group
Journal title: Asian journal of andrology
Volume: 13
Issue: 2
Start page: 236
End page: 241
Abstract: Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of S-(methoxytrityl)-L-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(MeO)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P<0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer.
Rights: © 2011 AJA, SIMM & SJTU.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
URI: http://hdl.handle.net/2433/156436
DOI(Published Version): 10.1038/aja.2010.171
PubMed ID: 21297652
Appears in Collections:Journal Articles

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