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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3320

Title: Tumor-inhibition effect of levetiracetam in combination with temozolomide in glioblastoma cells.
Other Titles: 膠芽腫細胞株におけるテモゾロミド併用によるレベチラセタムの抗腫瘍効果
Authors: Marutani, Akiko
Nakamura, Mitsutoshi
Nishimura, Fumihiko
Nakazawa, Tsutomu
Matsuda, Ryosuke
Hironaka, Yasuo
Nakagawa, Ichiro
Tamura, Kentaro
Takeshima, Yasuhiro
Motoyama, Yasushi
Boku, Eishu
Ouji, Yukiteru
Yoshikawa, Masahide
Nakase, Hiroyuki
Keywords: temozolomide
premature senescence
Issue Date: Jan-2017
Publisher: Springer
Citation: Neurochemical Journal Vol.11 No.1 p.43-49 (2017 Jan)
Abstract: Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. The standard postoperative chemotherapy is temozolomide (TMZ), which does not greatly improve survival. The DNA repair gene O-6-methylguanine-DNA methyltransferase (MGMT) contributes to the response of TMZ-induced DNA damage. The commonly prescribed antiepileptic drug levetiracetam (LEV) has been shown to enhance TMZ’s antitumor effect via inhibition of histone deacetylases (HDACs), but the therapeutic advantages of the LEV and TMZ combination remain poorly understood. Mechanisms of response to chemotherapy include apoptosis and mitotic catastrophe, and recent studies have suggested that premature senescence may also be invoked when cancer cells are exposed to therapeutic agents. In our study, we evaluated cell proliferation and premature senescence after single and combined treatments of TMZ and LEV in two GBM cell lines that differ in TMZ sensitivity caused by the absence (A172) or presence (T98) of the MGMT protein. Both LEV and TMZ reduced cell proliferation in a dose-dependent manner in A172 cells. A senescent-like phenotype, as determined by β-galactosidase activity, was induced by both TMZ and LEV. Overall, there was a greater effect following combined treatment compared to the monotherapy groups. Thus, LEV appears to have a tumor-suppressive effect and induces cellular senescence, and combined treatment of LEV and TMZ enhanced these effects. because LEV treatment results in few adverse effects, its use in GBM treatment may allow for reduction of the TMZ dose to enhance the clinical efficacy of TMZ chemotherapy and improve quality of life.
Description: 博士(医学)・甲第667号・平成29年3月15日
© Pleiades Publishing, Ltd. 2017
The final publication is available at Springer via http://dx.doi.org/10.1134/S1819712416040073
URI: http://hdl.handle.net/10564/3320
ISSN: 18197124
DOI: http://dx.doi.org/10.1134/S1819712416040073
Academic Degrees and number: 24601A667
Degree-granting date: 2017-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2016年度

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