High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide

Alessia Petronelli, Ernestina Saulle, Luca Pasquini, Eleonora Petrucci, Gualtiero Mariani, Mauro Biffoni, Gianluigi Ferretti, Giovanni Scambia, Pierluigi Benedetti-Panici, Stefano Greggi, Francesco Cognetti, Matteo Antonio Russo, Michael Sporn, Ugo Testa

Research output: Contribution to journalArticle

Abstract

In the present study we have explored the sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide (CDDO-Im). For these studies we have used the A2780 ovarian cancer cell line and its chemoresistant derivatives A2780/ADR and A2780/CISP, OVCAR3, SKOV3 and HEY cancer cell lines and primary ovarian cancer cells, providing evidence that: (i) the majority of these cell lines are highly sensitive to the pro-apoptotic effects induced by CDDO-Im; (ii) TRAIL, added alone exerted only a weak proapoptotic, but clearly potentiated the cytotoxic effect elicited by CDDO-Im; (iii) the apoptotic effect induced by CDDO-Im involves GSH depletion, c-FLIP downmodulation and caspase-8 activation; (iv) CDDO-Im inhibits STAT3 activation and CDDO-Im sensitivity is inversely related to the level of constitutive STAT3 activation. Importantly, studies on primary ovarian cancer cells have shown that these cells are sensitive to the pro-apoptotic effects of CDDO-Im. These observations support the experimental use of synthetic triterpenoids in the treatment of ovarian cancer.

Original languageEnglish
Pages (from-to)214-228
Number of pages15
JournalCancer Letters
Volume282
Issue number2
DOIs
Publication statusPublished - Sep 18 2009

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Artificial Cells
Ovarian Neoplasms
Cell Line
Caspase 8
Neoplasms

Keywords

  • Apoptosis
  • Chemoresistance
  • Ovarian cancer
  • Triterpens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Petronelli, A., Saulle, E., Pasquini, L., Petrucci, E., Mariani, G., Biffoni, M., ... Testa, U. (2009). High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide. Cancer Letters, 282(2), 214-228. https://doi.org/10.1016/j.canlet.2009.03.018

High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide. / Petronelli, Alessia; Saulle, Ernestina; Pasquini, Luca; Petrucci, Eleonora; Mariani, Gualtiero; Biffoni, Mauro; Ferretti, Gianluigi; Scambia, Giovanni; Benedetti-Panici, Pierluigi; Greggi, Stefano; Cognetti, Francesco; Russo, Matteo Antonio; Sporn, Michael; Testa, Ugo.

In: Cancer Letters, Vol. 282, No. 2, 18.09.2009, p. 214-228.

Research output: Contribution to journalArticle

Petronelli, A, Saulle, E, Pasquini, L, Petrucci, E, Mariani, G, Biffoni, M, Ferretti, G, Scambia, G, Benedetti-Panici, P, Greggi, S, Cognetti, F, Russo, MA, Sporn, M & Testa, U 2009, 'High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide', Cancer Letters, vol. 282, no. 2, pp. 214-228. https://doi.org/10.1016/j.canlet.2009.03.018
Petronelli A, Saulle E, Pasquini L, Petrucci E, Mariani G, Biffoni M et al. High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide. Cancer Letters. 2009 Sep 18;282(2):214-228. https://doi.org/10.1016/j.canlet.2009.03.018
Petronelli, Alessia ; Saulle, Ernestina ; Pasquini, Luca ; Petrucci, Eleonora ; Mariani, Gualtiero ; Biffoni, Mauro ; Ferretti, Gianluigi ; Scambia, Giovanni ; Benedetti-Panici, Pierluigi ; Greggi, Stefano ; Cognetti, Francesco ; Russo, Matteo Antonio ; Sporn, Michael ; Testa, Ugo. / High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide. In: Cancer Letters. 2009 ; Vol. 282, No. 2. pp. 214-228.
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