OBJECTIVE: Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536. MATERIALS AND METHODS: We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis. We have also examined the effect of the microenvironment on these parameters and the effects of BI 2536 in combination with other antimyeloma agents. RESULTS: We show that MM cell lines and patient samples express PLK1 and that cell death by apoptosis occurs when Plk1 is inhibited. Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells. CONCLUSIONS: Plk1 inhibition leads to cell death in MM cell lines and patient myeloma samples. Our data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma.
OBJECTIVE:Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536. MATERIALS AND METHODS: We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis. We have also examined the effect of the microenvironment on these parameters and the effects of BI 2536 in combination with other antimyeloma agents. RESULTS: We show that MM cell lines and patient samples express PLK1 and that cell death by apoptosis occurs when Plk1 is inhibited. Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells. CONCLUSIONS:Plk1 inhibition leads to cell death in MM cell lines and patientmyeloma samples. Our data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma.
Authors: Matthew D Christensen; Jacob J Elmer; Seron Eaton; Laura Gonzalez-Malerva; Joshua LaBaer; Kaushal Rege Journal: J Control Release Date: 2015-02-11 Impact factor: 9.776
Authors: María Sol Brassesco; Julia Alejandra Pezuk; Andressa Gois Morales; Jaqueline Carvalho de Oliveira; Gabriela Molinari Roberto; Glenda Nicioli da Silva; Harley Francisco de Oliveira; Carlos Alberto Scrideli; Luiz Gonzaga Tone Journal: Cancer Biol Ther Date: 2013-05-31 Impact factor: 4.742
Authors: Douglas W McMillin; Jake Delmore; Joseph Negri; Melissa Ooi; Steffen Klippel; Chandrasekhar V Miduturu; Nathanael S Gray; Paul G Richardson; Kenneth C Anderson; Andrew L Kung; Constantine S Mitsiades Journal: PLoS One Date: 2011-07-07 Impact factor: 3.240
Authors: Elena Díaz-Rodríguez; Stela Álvarez-Fernández; Xi Chen; Bruno Paiva; Ricardo López-Pérez; Juan Luis García-Hernández; Jesús F San Miguel; Atanasio Pandiella Journal: PLoS One Date: 2011-11-23 Impact factor: 3.240
Authors: Helen Jayne Susan Stewart; Gillian Abigail Horne; Sarah Bastow; Timothy James Telfer Chevassut Journal: Cancer Med Date: 2013-10-31 Impact factor: 4.452