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Article Open Access

Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin

  • Authors:
    • Rachel Morrison
    • Tiffany Lodge
    • Antonio Evidente
    • Robert Kiss
    • Helen Townley
  • View Affiliations / Copyright

    Affiliations: Department of Engineering Science, University of Oxford, Oxford, UK, Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK, Dipartimento di Scienze Chimiche, Universita di Napoli Federico II Complesso Universitario Monte Sant'Angelo, Naples, Italy, Laboratoire de Cancérologie et de Toxicologie Experimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium
    Copyright: © Morrison et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 773-786
    |
    Published online on: January 19, 2017
       https://doi.org/10.3892/ijo.2017.3858
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Abstract

Herein we have undertaken a systematic analysis of the effects of the fungal derivative ophiobolin A (OphA) on eight cancer cell lines from different tissue types. The LD50 for each cell line was determined and the change in cell size determined. Flow cytometric analysis and western blotting were used to assess the cell death markers for early apoptosis, late apoptosis and necrosis, and the involvement of the caspase signalling pathway. Alterations in calcium levels and reactive oxygen species were assessed due to their integral involvement in intracellular signalling. Subsequently, the endoplasmic reticulum (ER) and mitochondrial responses were investigated more closely. The extent of ER swelling, and the upregulation of proteins involved in the unfolded protein responses (UPR) were seen to vary according to cell line. The mitochondria were also shown to behave differently in response to the OphA in the different cell lines in terms of the change in membrane potential, the total area of mitochondria in the cell and the number of mitochondrial bifurcations. The data obtained in the present study indicate that the cancer cell lines tested are unable to successfully activate the ER stress/UPR responses, and that the mitochondria appear to be a central player in OphA-induced cancer cell death.
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Copy and paste a formatted citation
Spandidos Publications style
Morrison R, Lodge T, Evidente A, Kiss R and Townley H: Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin. Int J Oncol 50: 773-786, 2017.
APA
Morrison, R., Lodge, T., Evidente, A., Kiss, R., & Townley, H. (2017). Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin. International Journal of Oncology, 50, 773-786. https://doi.org/10.3892/ijo.2017.3858
MLA
Morrison, R., Lodge, T., Evidente, A., Kiss, R., Townley, H."Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin". International Journal of Oncology 50.3 (2017): 773-786.
Chicago
Morrison, R., Lodge, T., Evidente, A., Kiss, R., Townley, H."Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin". International Journal of Oncology 50, no. 3 (2017): 773-786. https://doi.org/10.3892/ijo.2017.3858
Copy and paste a formatted citation
x
Spandidos Publications style
Morrison R, Lodge T, Evidente A, Kiss R and Townley H: Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin. Int J Oncol 50: 773-786, 2017.
APA
Morrison, R., Lodge, T., Evidente, A., Kiss, R., & Townley, H. (2017). Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin. International Journal of Oncology, 50, 773-786. https://doi.org/10.3892/ijo.2017.3858
MLA
Morrison, R., Lodge, T., Evidente, A., Kiss, R., Townley, H."Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin". International Journal of Oncology 50.3 (2017): 773-786.
Chicago
Morrison, R., Lodge, T., Evidente, A., Kiss, R., Townley, H."Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin". International Journal of Oncology 50, no. 3 (2017): 773-786. https://doi.org/10.3892/ijo.2017.3858
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