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| Cytochrome P450 (CYP) epoxygenases have been detected in various human malignant diseases, suggesting potential roles of CYP epoxygenases and epoxyeicosatrienoic acids (EETs) in tumors. To understand the role of CYP-EETs in multiple myeloma (MM), we have investigated the effects of CYP epoxygenases inhibitor 17-octadecynoic acid (17-ODYA) on MM. In this study, we found that MM cell lines contained 11, 12-EET/14, 15-EET and increased EETs were detected in serum from MM patients. Addition of exogenous EETs promoted the proliferation of MM cells, whereas 17-ODYA inhibited the viability and exogenous EETs reversed 17-ODYA-mediated decrease of proliferation. 17-ODYA enhanced MM cells apoptosis and induced cells arrested at G0/G1 phase to suppress the proliferation of MM cells. 17-ODYA inhibited the motility and EETs levels of MM cells in a time-dependent manner. Incubated of MM cells with 17-ODYA resulted in the reduction of MMP-2 and MMP-9 gelatinolytic activity and protein expression. 17-ODYA down-regulated the phosphorylation of Akt, but had no effect on HIF-1α. These results reveal that CYP-EETs play an important role in promotion of the neoplastic phenotype of multiple myeloma and the inhibitor may be a new tool for MM treatment. |
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| Keywords:CYP epoxygenases; multiple myeloma; motility |
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