Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis

  • Authors:
    • Sayaka Yoshiba
    • Masayasu Iwase
    • Sayaka Kurihara
    • Makiko Uchida
    • Yuji Kurihara
    • Hitoshi Watanabe
    • Satoru Shintani
  • View Affiliations

  • Published online on: December 28, 2010     https://doi.org/10.3892/or.2010.1127
  • Pages: 645-652
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Abstract

Oral squamous cell carcinoma (OSCC) cells are relatively resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis during culture. We investigated the role of a proteaosome inhibitor in the survival and apoptosis of these cells. We found that the proteasome inhibitor MG132 markedly accelerated TRAIL-mediated apoptosis in OSCC cell lines HSC-2 and HSC-3. Addition of TRAIL to MG132-treated cells resulted in Bid cleavage. Furthermore, the inhibitors of caspase-3, caspase-8 and caspase-9 reduced the accelerative effect of MG132 on TRAIL-mediated apoptosis. These results suggest that the pro-apoptotic effect of a proteasome inhibitor on TRAIL-mediated apoptosis may contribute to both extrinsic and intrinsic pathways. MG132 enhanced the expression of the TRAIL receptors DR4 and DR5, and neutralization of DR5 receptors showed a marked reduction of TRAIL-mediated apoptosis, whereas that of DR4 was a partial reduction. MG132 also markedly reduced cellular FLICE-inhibitory protein (c-FLIP), cellular inhibitor of apoptosis protein-1 (cIAP-1), X-linked IAP (XIAP) and survivin. Therefore, MG132 provides partial regulation of TRAIL-mediated apoptosis in OSCC cells via modulation of DR5, c-FLIP, cIAP-1, XIAP and survivin. The proteasome inhibitor MG132 may therefore represent a novel strategy for overcoming resistance to TRAIL-mediated apoptosis in OSCC cells.

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March 2011
Volume 25 Issue 3

Print ISSN: 1021-335X
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Spandidos Publications style
Yoshiba S, Iwase M, Kurihara S, Uchida M, Kurihara Y, Watanabe H and Shintani S: Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis. Oncol Rep 25: 645-652, 2011
APA
Yoshiba, S., Iwase, M., Kurihara, S., Uchida, M., Kurihara, Y., Watanabe, H., & Shintani, S. (2011). Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis. Oncology Reports, 25, 645-652. https://doi.org/10.3892/or.2010.1127
MLA
Yoshiba, S., Iwase, M., Kurihara, S., Uchida, M., Kurihara, Y., Watanabe, H., Shintani, S."Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis". Oncology Reports 25.3 (2011): 645-652.
Chicago
Yoshiba, S., Iwase, M., Kurihara, S., Uchida, M., Kurihara, Y., Watanabe, H., Shintani, S."Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis". Oncology Reports 25, no. 3 (2011): 645-652. https://doi.org/10.3892/or.2010.1127