Open Access

Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL

  • Authors:
    • Tomohisa Ito
    • Takashi Ando
    • Miki Suzuki-Karasaki
    • Tomohiko Tokunaga
    • Yukihiro Yoshida
    • Toyoko Ochiai
    • Yasuaki Tokuhashi
    • Yoshihiro Suzuki-Karasaki
  • View Affiliations

  • Published online on: May 21, 2018     https://doi.org/10.3892/ijo.2018.4413
  • Pages: 503-514
  • Copyright: © Ito et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cold plasma-stimulated medium (PSM) are promising novel anticancer tools due to their strong anticancer activities and high tumor-selectivity. The present study demonstrated that PSM and TRAIL may trigger autophagy in human malignant melanoma and osteosarcoma cells. Live-cell imaging revealed that even under nutritional and stress-free conditions, these cells possessed a substantial level of autophagosomes, which were localized in the cytoplasm separately from tubular mitochondria. In response to cytotoxic levels of PSM, the mitochondria became highly fragmented, and aggregated and colocalized with the autophagosomes. The cytotoxic effects of PSM were suppressed in response to various pharmacological autophagy inhibitors, including 3-methyladenine (3-MA) and bafilomycin A1, thus indicating the induction of autophagic cell death (ACD). Lethal levels of PSM also resulted in non-apoptotic, non-autophagic cell death in a reactive oxygen species-dependent manner under certain circumstances. Furthermore, TRAIL exhibited only a modest cytotoxicity toward these tumor cells, and did not induce ACD and mitochondrial aberration. The combined use of TRAIL and subtoxic concentrations of 3-MA resulted in decreased basal autophagy, increased mitochondrial aberration, colocalization with autophagosomes and apoptosis. These results indicated that PSM may induce ACD, whereas TRAIL may trigger cytoprotective autophagy that compromises apoptosis. To the best of our knowledge, the present study is the first to demonstrate that PSM can induce ACD in human cancer cells. These findings provide a rationale for the advantage of PSM over TRAIL in the destruction of apoptosis-resistant melanoma and osteosarcoma cells.
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August-2018
Volume 53 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ito T, Ando T, Suzuki-Karasaki M, Tokunaga T, Yoshida Y, Ochiai T, Tokuhashi Y and Suzuki-Karasaki Y: Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL. Int J Oncol 53: 503-514, 2018.
APA
Ito, T., Ando, T., Suzuki-Karasaki, M., Tokunaga, T., Yoshida, Y., Ochiai, T. ... Suzuki-Karasaki, Y. (2018). Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL. International Journal of Oncology, 53, 503-514. https://doi.org/10.3892/ijo.2018.4413
MLA
Ito, T., Ando, T., Suzuki-Karasaki, M., Tokunaga, T., Yoshida, Y., Ochiai, T., Tokuhashi, Y., Suzuki-Karasaki, Y."Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL". International Journal of Oncology 53.2 (2018): 503-514.
Chicago
Ito, T., Ando, T., Suzuki-Karasaki, M., Tokunaga, T., Yoshida, Y., Ochiai, T., Tokuhashi, Y., Suzuki-Karasaki, Y."Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL". International Journal of Oncology 53, no. 2 (2018): 503-514. https://doi.org/10.3892/ijo.2018.4413