Top

Published in:

Open Access 01-04-2017 | Laboratory Investigation

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

Authors: 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

Published in: Journal of Neuro-Oncology | Issue 2/2017

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.

Available only for authorised users

Forst DA, Nahed BV, Loeffler JS, Batchelor TT (2014) Low-grade gliomas. Oncologist 19:403–413CrossRef

Ding B, Gao M, Li Z, Xu C, Fan S, He W (2015) Expression of TYMS in lymph node metastasis from low-grade glioma. Oncol Lett 10:1569–1574CrossRef

Sareddy GR, Kesanakurti D, Kirti PB, Babu PP (2013) Nonsteroidal anti-inflammatory drugs diclofenac and celecoxib attenuate Wnt/b-catenin/Tcf signaling pathway in human glioblastoma cells. Neurochem Res 38:2313–2322CrossRef

Sareddy GR, Geeviman K, Ramulu C, Babu PP (2012) The nonsteroidal anti-inflammatory drug celecoxib suppresses the growth and induces apoptosis of human glioblastoma cells via the NF-kB pathway. J Neurooncol 106:99–109CrossRef

Qiu Y, Li X, Yi B et al (2015) Protein phosphatase PHLPP induces cell apoptosis and exerts anticancer activity by inhibiting survivin phosphorylation and nuclear export in gallbladder cancer. Oncotarget 6:19148–19162PubMedPubMedCentral

Bai XM, Jiang H, Ding JX et al (2010) Prostaglandin E2 upregulates survivin expression via the EP1 receptor in hepatocellular carcinoma cells. Life Sci 86:214–223CrossRef

Xu K, Wang L, Shu HK (2014) COX-2 overexpression increases malignant potential of human glioma cells through Id1. Oncotarget 5:1241–1252PubMed

Vandeputte DA, Troost D, Leenstra S et al (2002) Expression and distribution of Id helix-loop-helix proteins in human astrocytic tumors. Glia 38:329–338CrossRef

Sampetrean O, Saga I, Nakanishi M, Sugihara E, Fukaya R, Onishi N, Osuka S, Akahata M, Kai K, Sugimoto H, Hirao A, Saya H (2011) Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells. Neoplasia 13:784–791CrossRef

10.

Saga I, Shibao S, Okubo J, Osuka S, Kobayashi Y, Yamada S, Fujita S, Urakami K, Kusuhara M, Yoshida K, Saya H, Sampetrean O (2014) Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model. Neurooncol 16:1048–1056

11.

Lee HC, Park IC, Park MJ et al. (2005) Sulindac and its metabolites inhibit invasion of glioblastoma cells via down-regulation of Akt/PKB and MMP-2. J Cell Biochem 94:597–610CrossRef

12.

Siegelin MD, Reuss DE, Habel A, Rami A, von Deimling A (2009) Quercetin promotes degradation of survivin and thereby enhances death-receptor-mediated apoptosis in glioma cells. Neurooncol 11:122–131

13.

Jin X, Yin J, Kim SH et al (2011) EGFR-Akt-smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction. Cancer Res 71:7125–7134CrossRef

14.

Joki T, Heese O, Nikas DC, Bello L, Zhang J, Kraeft SK, Seyfried NT, Abe T, Chen LB, Carroll RS, Black PM (2000) Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 60:4926–4931PubMed

15.

Panel V, Boëlle PY, Ayala-Sanmartin J et al (2006) Cytoplasmic phospholipase A2 expression in human colon adenocarcinoma is correlated with cyclooxygenase-2 expression and contributes to prostaglandin E2 production. Cancer Lett 243:255–263CrossRef

16.

Kern MA, Haugg AM, Koch AF et al (2006) Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma. Cancer Res 66:7059–7066CrossRef

17.

Kurtova AV, Xiao J, Mo Q et al (2015) Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 517:209–213CrossRef

18.

Arico S, Pattingre S, Bauvy C et al (2002) Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 277:27613–27621CrossRef

19.

Xie SQ, Zhang YH, Li Q et al (2012) COX-2-independent induction of apoptosis by celecoxib and polyamine naphthalimide conjugate mediated by polyamine depression in colorectal cancer cell lines. Int J Colorectal Dis 27:861–868CrossRef

20.

Mure H, Matsuzaki K, Kitazato KT et al. (2010) Akt2 and Akt3 play a pivotal role in malignant gliomas. Neurooncol 12:221–232

21.

Chautard E, Ouédraogo ZG, Biau J, Verrelle P (2014) Role of Akt in human malignant glioma: from oncogenesis to tumor aggressiveness. J Neurooncol 117:205–215CrossRef

22.

Dandekar DS, Lopez M, Carey RI, Lokeshwar BL (2005) Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells. Int J Cancer 115:484–492CrossRef

23.

Angileri FF, Aguennouz M, Conti A et al (2008) Nuclear factor-kappa B activation and differential expression of survivin and Bcl-2 in human grade 2–4 astrocytomas. Cancer 112:2258–2266CrossRef

24.

Phi JH, Choi SA, Lim SH et al (2013) ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma. BMC Cancer 13:1–16CrossRef

25.

Jin X, Jin X, Sohn YW et al (2013) Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression. Cancer Lett 328:235–242CrossRef

Title: Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma
Authors: 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
Publication date: 01-04-2017
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2380-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Early postoperative tumor progression predicts clinical outcome in glioblastoma—implication for clinical trials

The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease

Expression and prognostic value of microRNAs in lower-grade glioma depends on IDH1/2 status

Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Mesenchymal subtype of glioblastomas with high DNA-PKcs expression is associated with better response to radiotherapy and temozolomide