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.
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Authors | Yusuke Ohba, Yukiko Kanao, Nobuyoshi Morita, Eri Fujii, Mai Hohrai, Mayuko Takatsuji, Hideki Hirose, Daisaku Miura, Akihiro Watari, Masuo Yutsudo, Hanjun Zhao, Norikazu Yabuta, Akihiko Ito, Yasuyuki Kita, Hiroshi Nojima |
Journal | International journal of cancer
(Int J Cancer)
Vol. 121
Issue 1
Pg. 47-54
(Jul 01 2007)
ISSN: 0020-7136 [Print] United States |
PMID | 17290388
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Connexins
- GJB2 protein, human
- Gjb2 protein, mouse
- Oleic Acids
- Connexin 26
- oleylamide
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Topics |
- Animals
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Connexin 26
- Connexins
(classification, genetics, metabolism)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Molecular Structure
- Neoplasm Metastasis
(pathology, prevention & control)
- Oleic Acids
(chemical synthesis, chemistry, pharmacology)
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