BI2536 induces mitotic catastrophe and radiosensitization in human oral cancer cells

Oncotarget
Chieh-Yuan ChengYu-Jen Chen

Abstract

BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro. Male BALB/c nude mice implanted with SAS cells were used to examine the effects of BI2536 in vivo. Treatment with BI2536 preferentially inhibited the viability of SAS and OECM1 cells, but not the normal fibroblasts. Morphological examination and Annexin V/PI staining of BI2536-treated oral cancer cells showed mitotic catastrophe and apoptosis. A DNA histogram revealed BI2536 induced G2/M and upregulation of phosphorylated H3 indicating accumulation in the M phase. BI2536 modulated the expression of PLK1, cell division control ...Continue Reading

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Citations

Apr 26, 2019·Expert Opinion on Therapeutic Targets·Konstantinos Mintzas, Michael Heuser
Aug 1, 2020·The Journal of Biological Chemistry·Paula J BuckoJohn D Scott
Jul 9, 2021·Apoptosis : an International Journal on Programmed Cell Death·Xiaofeng DaiJianying Zhang

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Methods Mentioned

BETA
Flow cytometry
xenograft
transfection

Software Mentioned

SPSS Statistics
Cell Quest

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