The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells

  • Authors:
    • Antonietta Notaro
    • Selenia Sabella
    • Ornella Pellerito
    • Renza Vento
    • Giuseppe Calvaruso
    • Michela Giuliano
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  • Published online on: December 24, 2015     https://doi.org/10.3892/ijo.2015.3307
  • Pages: 1039-1044
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Abstract

Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosis demonstrating that WIN increased the level of SPARC protein and mRNA in a time-dependent manner. This event was functional to WIN/TRAIL-dependent apoptosis as demonstrated by RNA interfering analysis which indicated that SPARC-silenced cells were less sensitive to cytotoxic effects induced by the combined treatment. Our experiments also demonstrate that SPARC interacts with caspase-8 thus probably favoring its translocation to plasma membrane and the activation of extrinsic apoptotic pathway. In conclusion, to the best of our knowledge, our results are the first to show that WIN-dependent increase in the level of SPARC plays a critical role in sensitizing osteosarcoma cells to TRAIL action.
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March 2016
Volume 48 Issue 3

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

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APA
Notaro, A., Sabella, S., Pellerito, O., Vento, R., Calvaruso, G., & Giuliano, M. (2016). The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells. International Journal of Oncology, 48, 1039-1044. https://doi.org/10.3892/ijo.2015.3307
MLA
Notaro, A., Sabella, S., Pellerito, O., Vento, R., Calvaruso, G., Giuliano, M."The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells". International Journal of Oncology 48.3 (2016): 1039-1044.
Chicago
Notaro, A., Sabella, S., Pellerito, O., Vento, R., Calvaruso, G., Giuliano, M."The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells". International Journal of Oncology 48, no. 3 (2016): 1039-1044. https://doi.org/10.3892/ijo.2015.3307