A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells

Senthilkumar Kalimuthu; Prakash Gangadaran; Ji Min Oh; Ramya Lakshmi Rajendran; Ho Won Lee; Arunnehru Gopal; Chae Moon Hong; Yong Hyun Jeon; Shin Young Jeong; Sang Woo Lee; Jaetae Lee; Byeong Cheol Ahn

doi:10.1080/1061186X.2020.1745817

A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells

Senthilkumar Kalimuthu, Prakash Gangadaran, Ji Min Oh, Ramya Lakshmi Rajendran, Ho Won Lee, Arunnehru Gopal, Chae Moon Hong, Yong Hyun Jeon, Shin Young Jeong, Sang Woo Lee, Jaetae Lee, Byeong Cheol Ahn

Department of Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

Original language	English
Pages (from-to)	933-938
Number of pages	6
Journal	Journal of Drug Targeting
DOIs	https://doi.org/10.1080/1061186X.2020.1745817
State	Published - 2020

Keywords

bioluminescent imaging
cancer stem cells
Glioblastoma
sphere formation
tyrosine kinase inhibitor

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10.1080/1061186X.2020.1745817

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title = "A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells",

abstract = "Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.",

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author = "Senthilkumar Kalimuthu and Prakash Gangadaran and Oh, {Ji Min} and Rajendran, {Ramya Lakshmi} and Lee, {Ho Won} and Arunnehru Gopal and Hong, {Chae Moon} and Jeon, {Yong Hyun} and Jeong, {Shin Young} and Lee, {Sang Woo} and Jaetae Lee and Ahn, {Byeong Cheol}",

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year = "2020",

doi = "10.1080/1061186X.2020.1745817",

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T1 - A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells

AU - Kalimuthu, Senthilkumar

AU - Gangadaran, Prakash

AU - Oh, Ji Min

AU - Rajendran, Ramya Lakshmi

AU - Lee, Ho Won

AU - Gopal, Arunnehru

AU - Hong, Chae Moon

AU - Jeon, Yong Hyun

AU - Jeong, Shin Young

AU - Lee, Sang Woo

AU - Lee, Jaetae

AU - Ahn, Byeong Cheol

PY - 2020

Y1 - 2020

N2 - Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

AB - Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

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JO - Journal of Drug Targeting

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ER -

A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells

Abstract

Keywords

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