Effect of temozolomide on the viability of musculoskeletal sarcoma cells

  • Authors:
    • Yuta Kusabe
    • Hiroyuki Kawashima
    • Akira Ogose
    • Taro Sasaki
    • Takashi Ariizumi
    • Tetsuo Hotta
    • Naoto Endo
  • View Affiliations

  • Published online on: July 17, 2015     https://doi.org/10.3892/ol.2015.3506
  • Pages: 2511-2518
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Abstract

Musculoskeletal sarcomas (MSS) are a heterogeneous group of malignancies with relatively high mortality rates. The prognosis for patients with MSS is poor, with few drugs inducing measurable activity. Alkylating agents, namely ifosfamide and dacarbazine, which act nonspecifically on proliferating cells, are the typical therapy prescribed for advanced MSS. A novel alkylating agent, temozolomide (TMZ), has several advantages over existing alkylating agents. TMZ induces the formation of O6‑methylguanine in DNA, thereby inducing mismatches during DNA replication and the subsequent activation of apoptotic pathways. However, due to conflicting data in the literature, the mechanism of TMZ action has remained elusive. Therefore, the present study aimed to evaluate apoptosis in MSS cells treated with TMZ, and to evaluate the correlation between TMZ action and survival pathways, including the phosphoinositide 3‑kinase (PI3K)/Akt and extracellular signal‑regulated kinase (ERK)1/2 mitogen activated protein kinase (MAPK) pathways. Cell proliferation was evaluated by performing an XTT (sodium 3'‑[1‑(phenylaminocarbonyl)‑3,4‑tetrazolium]‑bis (4‑methoxy‑6‑nitro) benzene sulfonic acid hydrate) assay. Apoptotic morphological changes, for example chromatin condensation, were evaluated by fluorescence confocal microscopy. The expression of the apoptosis‑associated proteins caspase‑3, poly adenosine diphosphate ribose polymerase (PARP), Akt and ERK1/2, was determined by western blotting. The results of the present study indicated that, in certain MSS cells, the IC50 value was lower than that in TMZ‑sensitive U‑87 MG cells. Furthermore, TMZ treatment was associated with apoptotic morphological changes and the expression levels of pro‑apoptotic cleaved caspase‑3 and PARP were also increased in TMZ‑treated MSS cells. In addition, the results indicated that PI3K/Akt and ERK1/2 MAPK were constitutively phosphorylated in MSS cells, and phosphorylation of PI3K/Akt was suppressed in certain cells, and maintained in other cells, by TMZ. These observations emphasized the plasticity of MSS cells, and suggested that this plasticity may contribute to the variance in cell sensitivity to TMZ and TMZ-resistance in MSS.
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October-2015
Volume 10 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kusabe Y, Kawashima H, Ogose A, Sasaki T, Ariizumi T, Hotta T and Endo N: Effect of temozolomide on the viability of musculoskeletal sarcoma cells. Oncol Lett 10: 2511-2518, 2015
APA
Kusabe, Y., Kawashima, H., Ogose, A., Sasaki, T., Ariizumi, T., Hotta, T., & Endo, N. (2015). Effect of temozolomide on the viability of musculoskeletal sarcoma cells. Oncology Letters, 10, 2511-2518. https://doi.org/10.3892/ol.2015.3506
MLA
Kusabe, Y., Kawashima, H., Ogose, A., Sasaki, T., Ariizumi, T., Hotta, T., Endo, N."Effect of temozolomide on the viability of musculoskeletal sarcoma cells". Oncology Letters 10.4 (2015): 2511-2518.
Chicago
Kusabe, Y., Kawashima, H., Ogose, A., Sasaki, T., Ariizumi, T., Hotta, T., Endo, N."Effect of temozolomide on the viability of musculoskeletal sarcoma cells". Oncology Letters 10, no. 4 (2015): 2511-2518. https://doi.org/10.3892/ol.2015.3506