Oleamide derivatives are prototypical anti-metastasis drugs that act by inhibiting Connexin 26.
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.
Nojima
Hiroshi
H
Department of Molecular Genetics, Research Institute for Microbial Diseases, Graduate School of Pharmaceutical Science, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. snj-0212@biken.osaka-u.ac.jp
Ohba
Yusuke
Y
Kita
Yasuyuki
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000072259:Connexin 26; D017630:Connexins / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000473:pathology; D009829:Oleic Acids / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011379:Prognosis
D000970:Antineoplastic Agents; D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D009829:Oleic Acids; D000072259:Connexin 26; C029407:oleylamide