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Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26
Author(s) -
Ohba Yusuke,
Kanao Yukiko,
Morita Nobuyoshi,
Fujii Eri,
Hohrai Mai,
Takatsuji Mayuko,
Hirose Hideki,
Miura Daisaku,
Watari Akihiro,
Yutsudo Masuo,
Zhao Hanjun,
Yabuta Norikazu,
Ito Akihiko,
Kita Yasuyuki,
Nojima Hiroshi
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22608
Subject(s) - connexin , endosome , golgi apparatus , chemistry , hela , metastasis , intracellular , cancer research , microbiology and biotechnology , cytotoxic t cell , pharmacology , gap junction , biology , medicine , biochemistry , cancer , in vitro , cell
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. © 2007 Wiley‐Liss, Inc.