Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells

Chew Yee Ngan, Hirofumi Yamamoto, Akimitsu Takagi, Yujiro Fujie, Ichiro Takemasa, Masataka Ikeda, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri, Mitsugu Sekimoto, Nariaki Matsuura, Morito Monden

研究成果: ジャーナルへの寄稿記事

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The platinum-based chemotherapeutic agent oxaliplatin displays a wide range of antitumor activities. However, the underlying molecular responses to oxaliplatin in esophageal cancer remain largely unknown. In the present study, we investigated the effect of oxaliplatin on two esophageal cancer cell lines, squamous cell carcinoma (TE3) and adenocarcinoma (TE7). Following cell-cycle arrest at G2 phase after oxaliplatin treatment, TE3 cells died via apoptosis and TE7 cells died via mitotic catastrophe. Survivin was inhibited more in TE7 cells compared with TE3 cells, but inhibition of survivin using small interfering RNA induced mitotic catastrophe in both cell lines. Further investigations indicated that survivin promoter activity was also inhibited by oxaliplatin. Among mitotic catastrophe-associated proteins, 14-3-3σ was decreased in TE7 cells; no evident changes were observed for aurora kinases. Oxaliplatin-induced apoptosis in the TE3 cells was caspase dependent. However, downregulation of Bad, Bid, Puma, and Noxa, lack of cytochrome c release, and limited loss of mitochondrial membrane potential in early phase indicated possible initiation by pathways other than the mitochondrial pathway. Mechanistic studies showed that downregulation of survivin by oxaliplatin in TE7 cells was partially due to the proteasome-mediated protein degradation pathway and partially due to the downregulation of Sp1 transcription factor. Similar results were obtained for another gastric adenocarcinoma cell line, MKN45, in which survivin was previously shown to be inhibited by oxaliplatin. These data indicate that survivin may be a key target for oxaliplatin. The ability of oxaliplatin to induce different modes of cell death may contribute to its efficacy in esophageal cancer.

元の言語英語
ページ(範囲)129-139
ページ数11
ジャーナルCancer Science
99
発行部数1
DOI
出版物ステータス出版済み - 1 1 2008

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Ngan, C. Y., Yamamoto, H., Takagi, A., Fujie, Y., Takemasa, I., Ikeda, M., ... Monden, M. (2008). Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells. Cancer Science, 99(1), 129-139. https://doi.org/10.1111/j.1349-7006.2007.00637.x