RT Journal Article
SR Electronic
T1 Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2783
OP 2792
VO 36
IS 6
A1 MOTOFUMI SUZUKI
A1 TOHRU YAMAMORI
A1 HIRONOBU YASUI
A1 OSAMU INANAMI
YR 2016
UL http://ar.iiarjournals.org/content/36/6/2783.abstract
AB Background/Aim: The monopolar spindle 1 (MPS1) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To determine the possible relationship between MPS1 inhibition and genotoxic stress responses, herein we examined whether MPS1 inhibition influences cellular susceptibility towards two genotoxic treatments, etoposide and ionizing radiation (IR). Materials and Methods: Two murine tumour cell lines, SCCVII and EMT6, were used. The effect of genotoxic treatments with or without two novel MPS1 inhibitors, NMS-P715 and AZ3146, on cellular survival, cell-cycle distribution, centrosome status and mitotic catastrophe (MC) was evaluated. Results: MPS1 inhibition sensitized murine tumour cells to etoposide but not to IR. In addition, MPS1 inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced MC induced by etoposide but not by IR. Conclusion: MPS1 inhibition promotes the etoposide-induced aberrant mitosis and, consequently, the induction of tumour cell death.