title: Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells.
abstract: Cytochrome P450 (CYP) epoxygenases and the metabolites epoxyeicosatrienoic acids (EETs) exert multiple biological effects in various malignancies. We have previously found EETs to be secreted by multiple myeloma (MM) cells and to be involved in MM angiogenesis, but the role of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and mobility of MM cells remains unknown. In the present study, we found that MM cell lines generated detectable levels of 11,12-EET/14,15-EET and that increased levels of EETs were found in the serum of MM patients compared to healthy donors. The addition of exogenous EETs induced significantly enhanced proliferation of MM cells, whereas 17-octadecynoic acid (17-ODYA), an inhibitor of the CYP epoxygenase pathway, inhibited the viability and proliferation of MM cells. Moreover, this inhibitory effect could be successfully reversed by exogenous EETs. 17-ODYA also inhibited the motility of MM cells in a time-dependent manner, with a reduction of the gelatinolytic activity and protein expression of the matrix metalloproteinases (MMP)-2 and MMP-9. These results suggest the CYP epoxygenase pathway to be involved in the proliferation and invasion of MM cells, for which 17-ODYA could be a promising therapeutic drug.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China; Wuhan Central Hospital, Department of Hematology, Wuhan Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: Wuhan Central Hospital, Department of Hematology , Wuhan Hubei , China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Xiangyang Central Hospital, the Affiliated Hospital of Hubei University of Arts and Science, Department of Hematology , Xiangyang Hubei , China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan Hubei , China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan Hubei , China.
authors.forename: Qiubai
authors.initials: Q
authors.lastname: Li
keywords: Apoptosis; Cytochrome p450; Epoxyeicosatrienoic acids; Invasion; Migration; Multiple myeloma; Proliferation