title: Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway.
abstract: The small GTPases of the Ras and Rho families are widely involved in tumorigenesis and metastasis. We recently showed that YM529/ONO-5920, a new developed bisphosphonate, inhibits the mevalonate pathway, is required for the prenylation of the small GTPases. In this study, we investigated whether YM529/ONO-5920 inhibits tumor cell migration, invasion, adhesion, and metastasis in B16BL6 cells, a mouse melanoma cell line. It was found that YM529/ONO-5920 significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not show anti-proliferative effects on B16BL6 cells. YM529/ONO-5920 also inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, YM529/ONO-5920 suppressed Rho activation, but not activation of Ras. The results indicate that YM529/ONO-5920 suppresses the Rho/ROCK pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumour cell metastasis.
authors.affiliation: Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanimori
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tsubaki
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Yamazoe
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kidera
authors.forename: Masahi
authors.initials: M
authors.lastname: Yanae
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Junichi
authors.initials: J
authors.lastname: Kaneko
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529; D054460:rho-Associated Kinases