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Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells

Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells

Motofumi Suzuki, Tohru Yamamori, Hironobu Yasui, Osamu Inanami

Anticancer Res. 2016 Jun;36(6):2783-92.

PMID: 27272789

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1124329141	AZ3146		1124329-14-1	Price

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