A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

Eleonora Petrucci, Luca Pasquini, Alessia Petronelli, Ernestina Saulle, Gualtiero Mariani, Roberta Riccioni, Mauro Biffoni, Gianluigi Ferretti, Pieluigi Benedetti-Panici, Francesco Cognetti, Giovanni Scambia, Robin Humphreys, Cesare Peschle, Ugo Testa

Research output: Contribution to journalArticle

Abstract

Objectives.: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. Methods.: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. Results.: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. Conclusions.: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.

Original languageEnglish
Pages (from-to)481-492
Number of pages12
JournalGynecologic Oncology
Volume105
Issue number2
DOIs
Publication statusPublished - May 2007

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Keywords

  • Apoptosis
  • Ovarian cancer
  • Smac/DIABLO
  • TRAIL

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Petrucci, E., Pasquini, L., Petronelli, A., Saulle, E., Mariani, G., Riccioni, R., Biffoni, M., Ferretti, G., Benedetti-Panici, P., Cognetti, F., Scambia, G., Humphreys, R., Peschle, C., & Testa, U. (2007). A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells. Gynecologic Oncology, 105(2), 481-492. https://doi.org/10.1016/j.ygyno.2007.01.011