NDLI: A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xing, Nai-Dong Ding, Sen-Tai Saito, Ryoichi Nishizawa, Koji Kobayashi, Takashi Inoue, Takahiro Oishi, Shinya Fujii, Nobutaka Lv, Jia-Jv Ogawa, Osamu Nishiyama, Hiroyuki
Description	Country affiliation: Japan Author Affiliation: Xing ND ( Department of Urology, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan.)
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.
File Format	HTM / HTML
ISSN	1008682X
e-ISSN	17457262
DOI	10.1038/aja.2010.171
Journal	Asian Journal of Andrology
Issue Number	2
Volume Number	13
Language	English
Publisher	Wolters Kluwer - Medknow
Publisher Date	2011-03-01
Publisher Place	China
Access Restriction	Open
Subject Keyword	Discipline Urology Antineoplastic Agents Therapeutic Use Cysteine Analogs & Derivatives Kinesin Antagonists & Inhibitors Prostatic Neoplasms Drug Therapy Trityl Compounds Animals Tumor Markers, Biological Metabolism Cell Line, Tumor Cell Survival Drug Effects Drug Resistance, Neoplasm Mice Mice, Nude Pathology Protein Array Analysis Taxoids Xenograft Model Antitumor Assays Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Urology

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