Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species

  • Authors:
    • Motoya Tanaka
    • Yuji Miura
    • Hiroki Numanami
    • Sivasundaram Karnan
    • Akinobu Ota
    • Hiroyuki Konishi
    • Yoshitaka Hosokawa
    • Masayuki Hanyuda
  • View Affiliations

  • Published online on: July 27, 2015     https://doi.org/10.3892/or.2015.4155
  • Pages: 1726-1732
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Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor that is characterized by dysregulated growth and resistance to apoptosis. Reactive oxygen species (ROS)-generating NADPH oxidase (Nox) family enzymes have been suggested to be involved in neoplastic proliferation. Both the antioxidant N-acetylcysteine (NAC) and the inhibitor of flavoprotein-dependent oxidase, diphenylene iodonium (DPI), inhibited the cell viability of MPM cells in a dose-dependent manner. To examine whether Nox-mediated ROS generation confers antiapoptotic activity and thus a growth advantage to MPM cells, we analyzed the mRNA expression of Nox family members using quantitative RT-PCR in 7 MPM cell lines and a normal mesothelial cell line. Nox4 mRNA was expressed in all of the examined MPM cell lines, whereas little or no Nox2, Nox3 and Nox5 mRNA expression was detected. In 2 MPM cell lines, Nox4 mRNA expression was significantly higher than that in a normal mesothelial cell line. siRNAs targeting Nox4 suppressed ROS generation and cell viability in the MPM cell lines. In addition, DPI treatment and knockdown of Nox4 attenuated phosphorylation of AKT and ERK. Taken together, our results indicate that Nox4-mediated ROS, at least in part, transmit cell survival signals and their depletion leads to apoptosis, thus highlighting the Nox4-ROS-AKT signaling pathway as a potential therapeutic target for MPM treatment.
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October-2015
Volume 34 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tanaka M, Miura Y, Numanami H, Karnan S, Ota A, Konishi H, Hosokawa Y and Hanyuda M: Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species. Oncol Rep 34: 1726-1732, 2015.
APA
Tanaka, M., Miura, Y., Numanami, H., Karnan, S., Ota, A., Konishi, H. ... Hanyuda, M. (2015). Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species. Oncology Reports, 34, 1726-1732. https://doi.org/10.3892/or.2015.4155
MLA
Tanaka, M., Miura, Y., Numanami, H., Karnan, S., Ota, A., Konishi, H., Hosokawa, Y., Hanyuda, M."Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species". Oncology Reports 34.4 (2015): 1726-1732.
Chicago
Tanaka, M., Miura, Y., Numanami, H., Karnan, S., Ota, A., Konishi, H., Hosokawa, Y., Hanyuda, M."Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species". Oncology Reports 34, no. 4 (2015): 1726-1732. https://doi.org/10.3892/or.2015.4155