Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis

Seok Soon Park; Young Jong Kim; Eun Jin Ju; Seol Hwa Shin; Jinhyang Choi; Jaesook Park; Jae Hee Lee; Kyoung Jin Lee; Jin Park; Hye Ji Park; Eun Jung Ko; Jung Jin Hwang; Dong Hoon Jin; Nayoung Suh; Dong Hyung Cho; Jung Shin Lee; Si Yeol Song; B. Moon Kim; Seong Yun Jeong; Eun Kyung Choi

doi:10.1016/j.radonc.2014.07.005

Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis

Seok Soon Park, Young Jong Kim, Eun Jin Ju, Seol Hwa Shin, Jinhyang Choi, Jaesook Park, Jae Hee Lee, Kyoung Jin Lee, Jin Park, Hye Ji Park, Eun Jung Ko, Jung Jin Hwang, Dong Hoon Jin, Nayoung Suh, Dong Hyung Cho, Jung Shin Lee, Si Yeol Song, B. Moon Kim, Seong Yun Jeong, Eun Kyung Choi

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

12 Scopus citations

Abstract

Background and purpose Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.

Material and methods Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.

Results Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB.

Conclusions IB demonstrated the property of sensitizing human cancer cells to RT by induction of mitochondria-mediated apoptosis, suggesting that IB deserves to be applied for chemoradiotherapy.

Original language	English
Pages (from-to)	295-301
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	112
Issue number	2
DOIs	https://doi.org/10.1016/j.radonc.2014.07.005
State	Published - 1 Aug 2014

Keywords

Apoptosis
Bcl-2
Caspase
Ibulocydine
Mitochondria
Radiotherapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.radonc.2014.07.005

Cite this

Park, S. S., Kim, Y. J., Ju, E. J., Shin, S. H., Choi, J., Park, J., Lee, J. H., Lee, K. J., Park, J., Park, H. J., Ko, E. J., Hwang, J. J., Jin, D. H., Suh, N., Cho, D. H., Lee, J. S., Song, S. Y., Kim, B. M., Jeong, S. Y., & Choi, E. K. (2014). Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis. Radiotherapy and Oncology, 112(2), 295-301. https://doi.org/10.1016/j.radonc.2014.07.005

@article{7b457185a14d4cd1b4a92495fb0775df,

title = "Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis",

abstract = "Background and purpose Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.Material and methods Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.Results Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB.Conclusions IB demonstrated the property of sensitizing human cancer cells to RT by induction of mitochondria-mediated apoptosis, suggesting that IB deserves to be applied for chemoradiotherapy.",

keywords = "Apoptosis, Bcl-2, Caspase, Ibulocydine, Mitochondria, Radiotherapy",

author = "Park, {Seok Soon} and Kim, {Young Jong} and Ju, {Eun Jin} and Shin, {Seol Hwa} and Jinhyang Choi and Jaesook Park and Lee, {Jae Hee} and Lee, {Kyoung Jin} and Jin Park and Park, {Hye Ji} and Ko, {Eun Jung} and Hwang, {Jung Jin} and Jin, {Dong Hoon} and Nayoung Suh and Cho, {Dong Hyung} and Lee, {Jung Shin} and Song, {Si Yeol} and Kim, {B. Moon} and Jeong, {Seong Yun} and Choi, {Eun Kyung}",

year = "2014",

month = aug,

day = "1",

doi = "10.1016/j.radonc.2014.07.005",

language = "English",

volume = "112",

pages = "295--301",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

number = "2",

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Park, SS, Kim, YJ, Ju, EJ, Shin, SH, Choi, J, Park, J, Lee, JH, Lee, KJ, Park, J, Park, HJ, Ko, EJ, Hwang, JJ, Jin, DH, Suh, N, Cho, DH, Lee, JS, Song, SY, Kim, BM, Jeong, SY & Choi, EK 2014, 'Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis', Radiotherapy and Oncology, vol. 112, no. 2, pp. 295-301. https://doi.org/10.1016/j.radonc.2014.07.005

TY - JOUR

T1 - Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis

AU - Park, Seok Soon

AU - Kim, Young Jong

AU - Ju, Eun Jin

AU - Shin, Seol Hwa

AU - Choi, Jinhyang

AU - Park, Jaesook

AU - Lee, Jae Hee

AU - Lee, Kyoung Jin

AU - Park, Jin

AU - Park, Hye Ji

AU - Ko, Eun Jung

AU - Hwang, Jung Jin

AU - Jin, Dong Hoon

AU - Suh, Nayoung

AU - Cho, Dong Hyung

AU - Lee, Jung Shin

AU - Song, Si Yeol

AU - Kim, B. Moon

AU - Jeong, Seong Yun

AU - Choi, Eun Kyung

PY - 2014/8/1

Y1 - 2014/8/1

N2 - Background and purpose Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.Material and methods Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.Results Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB.Conclusions IB demonstrated the property of sensitizing human cancer cells to RT by induction of mitochondria-mediated apoptosis, suggesting that IB deserves to be applied for chemoradiotherapy.

AB - Background and purpose Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.Material and methods Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.Results Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB.Conclusions IB demonstrated the property of sensitizing human cancer cells to RT by induction of mitochondria-mediated apoptosis, suggesting that IB deserves to be applied for chemoradiotherapy.

KW - Apoptosis

KW - Bcl-2

KW - Caspase

KW - Ibulocydine

KW - Mitochondria

KW - Radiotherapy

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U2 - 10.1016/j.radonc.2014.07.005

DO - 10.1016/j.radonc.2014.07.005

M3 - Article

C2 - 25082098

AN - SCOPUS:84911003588

SN - 0167-8140

VL - 112

SP - 295

EP - 301

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

IS - 2

ER -

Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondria-mediated apoptosis

Abstract

Keywords

UN SDGs

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