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
Cancer Letters 2009 September 18, 282 (2): 214-28
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.

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