Abstract
Despite considerable research, metastasis remains a major challenge in the clinical management of cancer. Recent reports show that abnormally augmented expression of Cx26 is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells. The function of Cx26 appears to be responsible for this phenotype since exogenous expression of a dominant-negative form of Cx26 and oleamide derivatives called MI-18 and MI-22 that specifically inhibit Cx26-mediated gap junction-mediated intercellular communications (GJIC) prevent the spontaneous metastasis of BL6 cells. As expected from their structural similarity to oleic acid (the major component of olive oil), both MI-18 and MI-22 are safe drugs; nonetheless, they are potent inhibitors of the spontaneous metastasis of BL6 mouse melanoma cells. Thus, they are a novel prototype of an anti-metastasis drug that has minimal side effects. While the primary tumors do not necessarily show strong Cx26-immunostaining signals, pronounced Cx26 expression is detected in the highly invasive tumor regions; it is also more frequently observed in metastasized tumors. Thus, Cx26 expression may be useful as a prognostic tool that can predict the existence of highly metastatic cancer cells in clinical samples.
Keywords: BL6, connexin-26, metastasis, oleamide, gap junction, hemichannel
Current Drug Safety
Title: Oleamide Derivatives are Prototypical Anti-Metastasis Drugs that Act by Inhibiting Connexin 26
Volume: 2 Issue: 3
Author(s): Hiroshi Nojima, Yusuke Ohba and Yasuyuki Kita
Affiliation:
Keywords: BL6, connexin-26, metastasis, oleamide, gap junction, hemichannel
Abstract: Despite considerable research, metastasis remains a major challenge in the clinical management of cancer. Recent reports show that abnormally augmented expression of Cx26 is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells. The function of Cx26 appears to be responsible for this phenotype since exogenous expression of a dominant-negative form of Cx26 and oleamide derivatives called MI-18 and MI-22 that specifically inhibit Cx26-mediated gap junction-mediated intercellular communications (GJIC) prevent the spontaneous metastasis of BL6 cells. As expected from their structural similarity to oleic acid (the major component of olive oil), both MI-18 and MI-22 are safe drugs; nonetheless, they are potent inhibitors of the spontaneous metastasis of BL6 mouse melanoma cells. Thus, they are a novel prototype of an anti-metastasis drug that has minimal side effects. While the primary tumors do not necessarily show strong Cx26-immunostaining signals, pronounced Cx26 expression is detected in the highly invasive tumor regions; it is also more frequently observed in metastasized tumors. Thus, Cx26 expression may be useful as a prognostic tool that can predict the existence of highly metastatic cancer cells in clinical samples.
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Nojima Hiroshi, Ohba Yusuke and Kita Yasuyuki, Oleamide Derivatives are Prototypical Anti-Metastasis Drugs that Act by Inhibiting Connexin 26, Current Drug Safety 2007; 2 (3) . https://dx.doi.org/10.2174/157488607781668837
DOI https://dx.doi.org/10.2174/157488607781668837 |
Print ISSN 1574-8863 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3911 |
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