title: Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26.
abstract: We previously reported that overexpressing connexin 26 (Cx26) enhances the spontaneous metastasis of mouse BL6 melanoma cells. In contrast, daily intraperitoneal injections of an oleamide derivative named MI-18 potently inhibits the spontaneous metastasis of BL6 cells. In the present study, we chemically synthesized a novel oleamide derivative named MI-22 and found that it also efficiently suppressed the spontaneous metastasis of BL6 cells. Both MI-18 and MI-22 inhibited the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of the hCx26 and hCx32 human connexin subtypes; however, they had no effect on GJIC mediated by hCx40, hCx43 or hCx45. Fluorescently labeled MI-18 primarily localized not only at plasma membrane but also at Golgi/endosome. This suggests that this oleamide derivative may also act on the Cx26 molecules that accumulate in the Golgi/endosome because of their overexpression. Notably, neither derivative had a cytotoxic effect on HeLa cells when they were added into the tissue culture medium. Taken together, we propose that the MI-18 and MI-22 oleamide derivatives may serve as prototypes for novel and clinically important anticancer drugs.
authors.affiliation: Department of Synthetic Organic Chemistry, Graduate School of Pharmaceutical Science, Osaka University, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanao
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Morita
authors.forename: Eri
authors.initials: E
authors.lastname: Fujii
authors.forename: Mai
authors.initials: M
authors.lastname: Hohrai
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takatsuji
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirose
authors.forename: Daisaku
authors.initials: D
authors.lastname: Miura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watari
authors.forename: Masuo
authors.initials: M
authors.lastname: Yutsudo
authors.forename: Hanjun
authors.initials: H
authors.lastname: Zhao
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yabuta
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ito
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000072259:Connexin 26; D017630:Connexins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009829:Oleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D009829:Oleic Acids; D000072259:Connexin 26; C029407:oleylamide