Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma

Aya Sato; Yoshifumi Mizobuchi; Kohei Nakajima; Kenji Shono; Toshitaka Fujihara; Teruyoshi Kageji; Keiko Kitazato; Kazuhito Matsuzaki; Hideo Mure; Kazuyuki Kuwayama; Akiko Sumi; Hideyuki Saya; Oltea Sampetrean; Shinji Nagahirao

doi:10.1007/s11060-017-2380-5

Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma

Aya Sato, Yoshifumi Mizobuchi, Kohei Nakajima, Kenji Shono, Toshitaka Fujihara, Teruyoshi Kageji, Keiko Kitazato, Kazuhito Matsuzaki, Hideo Mure, Kazuyuki Kuwayama, Akiko Sumi, Hideyuki Saya, Oltea Sampetrean, Shinji Nagahirao

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

21 Citations (Scopus)

Abstract

Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.

Original language	English
Pages (from-to)	231-238
Number of pages	8
Journal	Journal of Neuro-Oncology
Volume	132
Issue number	2
DOIs	https://doi.org/10.1007/s11060-017-2380-5
Publication status	Published - 2017 Apr 1

Keywords

Akt
COX-2
ID3
Low-grade glioma
Survivin

ASJC Scopus subject areas

Oncology
Neurology
Clinical Neurology
Cancer Research

UN SDGs

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

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10.1007/s11060-017-2380-5

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Sato, A., Mizobuchi, Y., Nakajima, K., Shono, K., Fujihara, T., Kageji, T., Kitazato, K., Matsuzaki, K., Mure, H., Kuwayama, K., Sumi, A., Saya, H., Sampetrean, O., & Nagahirao, S. (2017). Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma. Journal of Neuro-Oncology, 132(2), 231-238. https://doi.org/10.1007/s11060-017-2380-5

Sato, A, Mizobuchi, Y, Nakajima, K, Shono, K, Fujihara, T, Kageji, T, Kitazato, K, Matsuzaki, K, Mure, H, Kuwayama, K, Sumi, A, Saya, H, Sampetrean, O & Nagahirao, S 2017, 'Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma', Journal of Neuro-Oncology, vol. 132, no. 2, pp. 231-238. https://doi.org/10.1007/s11060-017-2380-5

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title = "Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma",

abstract = "Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.",

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doi = "10.1007/s11060-017-2380-5",

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AU - Sato, Aya

AU - Mizobuchi, Yoshifumi

AU - Nakajima, Kohei

AU - Shono, Kenji

AU - Fujihara, Toshitaka

AU - Kageji, Teruyoshi

AU - Kitazato, Keiko

AU - Matsuzaki, Kazuhito

AU - Mure, Hideo

AU - Kuwayama, Kazuyuki

AU - Sumi, Akiko

AU - Saya, Hideyuki

AU - Sampetrean, Oltea

AU - Nagahirao, Shinji

N1 - Funding Information: This work was supported by a Grant-in-Aid for Scientific Research (JSPS KAKENHI Grant Number JP25462264), a Grant-in-Aid for Young Scientists (B) (JSPS KAKENHI Grant Number JP26861153). Publisher Copyright: © 2017, Springer Science+Business Media New York.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.

AB - Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.

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Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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