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Article

Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity

  • Authors:
    • Marina Bury
    • Esther Novo-Uzal
    • Anna Andolfi
    • Sara Cimini
    • Nathalie Wauthoz
    • Petra Heffeter
    • Benjamin Lallemand
    • Fabiana Avolio
    • Cédric Delporte
    • Alessio Cimmino
    • Jacques Dubois
    • Pierre Van Antwerpen
    • Maria Chiara Zonno
    • Maurizio Vurro
    • Yves Poumay
    • Walter Berger
    • Antonio Evidente
    • Laura De Gara
    • Robert Kiss
    • Vittoria Locato
  • View Affiliations / Copyright

    Affiliations: Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium, Centro Integrato di Ricerca, Università Campus Bio-Medico, Rome, Italy, Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, I-80126 Naples, Italy, Laboratoire de Pharmacie Galénique et de Biopharmacie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium, Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria, Laboratoire de Chimie BioAnalytique, Toxicologie et Chimie Physique Appliquée, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium, Laboratoire de Chimie Pharmaceutique Organique, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium, Istituto di Scienze delle Produzioni Alimentari, Consiglio Nazionale delle Ricerche, Bari, Italy, Cell and Tissue Laboratory, URPHYM, Université de Namur, Namur, Belgium
  • Pages: 575-585
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    Published online on: June 10, 2013
       https://doi.org/10.3892/ijo.2013.1979
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Abstract

Ophiobolin A, a sesterterpenoid produced by plant pathogenic fungi, was purified from the culture extract of Drechslera gigantea and tested for its growth-inhibitory activity in both plant and mammalian cells. Ophiobolin A induced cell death in Nicotiana tabacum L. cv. Bright Yellow 2 (TBY-2) cells at concentrations ≥10 µM, with the TBY-2 cells showing typical features of apoptosis-like cell death. At a concentration of 5 µM, ophiobolin A did not affect plant cell viability but prevented cell proliferation. When tested on eight cancer cell lines, concentrations <1 µM of ophiobolin A inhibited growth by 50% after 3 days of culture irrespective of their multidrug resistance (MDR) phenotypes and their resistance levels to pro-apoptotic stimuli. It is, thus, unlikely that ophiobolin A exerts these in vitro growth-inhibitory effects in cancer cells by activating pro-apoptotic processes. Highly proliferative human keratinocytes appeared more sensitive to the growth-inhibitory effects of ophiobolin A than slowly proliferating ones. Ophiobolin A also displayed significant antitumor activity at the level of mouse survival when assayed at 10 mg/kg in the B16F10 mouse melanoma model with lung pseudometastases. Ophiobolin A could, thus, represent a novel scaffold to combat cancer types that display various levels of resistance to pro-apoptotic stimuli and/or various MDR phenotypes.
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Copy and paste a formatted citation
Spandidos Publications style
Bury M, Novo-Uzal E, Andolfi A, Cimini S, Wauthoz N, Heffeter P, Lallemand B, Avolio F, Delporte C, Cimmino A, Cimmino A, et al: Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity. Int J Oncol 43: 575-585, 2013.
APA
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P. ... Locato, V. (2013). Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity. International Journal of Oncology, 43, 575-585. https://doi.org/10.3892/ijo.2013.1979
MLA
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P., Lallemand, B., Avolio, F., Delporte, C., Cimmino, A., Dubois, J., Van Antwerpen, P., Zonno, M. C., Vurro, M., Poumay, Y., Berger, W., Evidente, A., De Gara, L., Kiss, R., Locato, V."Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity". International Journal of Oncology 43.2 (2013): 575-585.
Chicago
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P., Lallemand, B., Avolio, F., Delporte, C., Cimmino, A., Dubois, J., Van Antwerpen, P., Zonno, M. C., Vurro, M., Poumay, Y., Berger, W., Evidente, A., De Gara, L., Kiss, R., Locato, V."Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity". International Journal of Oncology 43, no. 2 (2013): 575-585. https://doi.org/10.3892/ijo.2013.1979
Copy and paste a formatted citation
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Spandidos Publications style
Bury M, Novo-Uzal E, Andolfi A, Cimini S, Wauthoz N, Heffeter P, Lallemand B, Avolio F, Delporte C, Cimmino A, Cimmino A, et al: Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity. Int J Oncol 43: 575-585, 2013.
APA
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P. ... Locato, V. (2013). Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity. International Journal of Oncology, 43, 575-585. https://doi.org/10.3892/ijo.2013.1979
MLA
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P., Lallemand, B., Avolio, F., Delporte, C., Cimmino, A., Dubois, J., Van Antwerpen, P., Zonno, M. C., Vurro, M., Poumay, Y., Berger, W., Evidente, A., De Gara, L., Kiss, R., Locato, V."Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity". International Journal of Oncology 43.2 (2013): 575-585.
Chicago
Bury, M., Novo-Uzal, E., Andolfi, A., Cimini, S., Wauthoz, N., Heffeter, P., Lallemand, B., Avolio, F., Delporte, C., Cimmino, A., Dubois, J., Van Antwerpen, P., Zonno, M. C., Vurro, M., Poumay, Y., Berger, W., Evidente, A., De Gara, L., Kiss, R., Locato, V."Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity". International Journal of Oncology 43, no. 2 (2013): 575-585. https://doi.org/10.3892/ijo.2013.1979
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