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December 2012 Volume 41 Issue 6

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Article

Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis

  • Authors:
    • Mayumi Murai
    • Toshio Inoue
    • Miki Suzuki-Karasaki
    • Toyoko Ochiai
    • Chisei Ra
    • Sigeru Nishida
    • Yoshihiro Suzuki-Karasaki
  • View Affiliations / Copyright

    Affiliations: Division of Molecular Cell Immunology and Allergology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan, Department of Dermatology, Nihon University Surugadai Hospital, Tokyo, Japan, Department of Chemistry, Nihon University School of Medicine, Tokyo, Japan
  • Pages: 2029-2037
    |
    Published online on: October 11, 2012
       https://doi.org/10.3892/ijo.2012.1656
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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment because of its selective cytotoxicity toward tumor cells. However, some cancer cell types including malignant melanoma cells are resistant to TRAIL cytotoxicity. Here, we show that diallyl trisulfide (DATS), a garlic organosulfur compound, sensitizes melanoma cells to TRAIL-induced apoptosis while sparing normal cells. DATS also potentiates apoptosis induced by agonistic antibodies against death receptors (DR) 4 and DR5. The amplification of DR-mediated apoptosis was associated with increased mitochondrial membrane potential collapse and caspase-3/7 activation. However, these events were not sufficient for full sensitization. TRAIL also induced endoplasmic reticulum (ER) stress, as indicated by the activation of X-box-binding protein 1 and caspase-12 and DATS poten­tiated both events. Moreover, inhibition of caspase-12, but not caspase-4, abolished the amplification of apoptosis, indicating that ER stress plays a crucial role. On the other hand, DATS and/or TRAIL induced minimal apoptosis and caspase-12 activation in melanocytes despite their substantial expression of DR4 and DR5 on the cell surface. Our data suggest that DATS amplifies death ligand-induced melanoma cell death by disrupting their adaptation to ER-mediated death pathway. The present findings raise the possibility that DATS may be combined with death ligands to treat TRAIL-resistance melanoma cells without impairing its tumor selectivity.
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Copy and paste a formatted citation
Spandidos Publications style
Murai M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C, Nishida S and Suzuki-Karasaki Y: Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis. Int J Oncol 41: 2029-2037, 2012.
APA
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., & Suzuki-Karasaki, Y. (2012). Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis. International Journal of Oncology, 41, 2029-2037. https://doi.org/10.3892/ijo.2012.1656
MLA
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., Suzuki-Karasaki, Y."Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis". International Journal of Oncology 41.6 (2012): 2029-2037.
Chicago
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., Suzuki-Karasaki, Y."Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis". International Journal of Oncology 41, no. 6 (2012): 2029-2037. https://doi.org/10.3892/ijo.2012.1656
Copy and paste a formatted citation
x
Spandidos Publications style
Murai M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C, Nishida S and Suzuki-Karasaki Y: Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis. Int J Oncol 41: 2029-2037, 2012.
APA
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., & Suzuki-Karasaki, Y. (2012). Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis. International Journal of Oncology, 41, 2029-2037. https://doi.org/10.3892/ijo.2012.1656
MLA
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., Suzuki-Karasaki, Y."Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis". International Journal of Oncology 41.6 (2012): 2029-2037.
Chicago
Murai, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Nishida, S., Suzuki-Karasaki, Y."Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis". International Journal of Oncology 41, no. 6 (2012): 2029-2037. https://doi.org/10.3892/ijo.2012.1656
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