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

  • Published online on: June 10, 2013     https://doi.org/10.3892/ijo.2013.1979
  • Pages: 575-585
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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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August 2013
Volume 43 Issue 2

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

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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