PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression

Germano Mariano, Maria Rosaria Ricciardi, Daniela Trisciuoglio, Michele Zampieri, Fabio Ciccarone, Tiziana Guastafierro, Roberta Calabrese, Elisabetta Valentini, Agostino Tafuri, Donatella Del Bufalo, Paola Caiafa, Anna Reale

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADPribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating antiapoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDAMB- 231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosis.

Original languageEnglish
Pages (from-to)15008-15021
Number of pages14
JournalOncotarget
Volume6
Issue number17
Publication statusPublished - 2015

Fingerprint

Snails
Doxorubicin
Poly(ADP-ribose) Polymerases
Apoptosis
Neoplasms
Epithelial-Mesenchymal Transition
Cytotoxins
Post Translational Protein Processing
Adenosine Diphosphate
Pharmacology
Breast Neoplasms
Cell Line
veliparib
Poly(ADP-ribose) Polymerase Inhibitors
Therapeutics
Genes

Keywords

  • Breast cancer
  • Chemoresistance
  • PARP inhibitors
  • Snail

ASJC Scopus subject areas

  • Oncology

Cite this

Mariano, G., Ricciardi, M. R., Trisciuoglio, D., Zampieri, M., Ciccarone, F., Guastafierro, T., ... Reale, A. (2015). PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression. Oncotarget, 6(17), 15008-15021.

PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression. / Mariano, Germano; Ricciardi, Maria Rosaria; Trisciuoglio, Daniela; Zampieri, Michele; Ciccarone, Fabio; Guastafierro, Tiziana; Calabrese, Roberta; Valentini, Elisabetta; Tafuri, Agostino; Del Bufalo, Donatella; Caiafa, Paola; Reale, Anna.

In: Oncotarget, Vol. 6, No. 17, 2015, p. 15008-15021.

Research output: Contribution to journalArticle

Mariano, G, Ricciardi, MR, Trisciuoglio, D, Zampieri, M, Ciccarone, F, Guastafierro, T, Calabrese, R, Valentini, E, Tafuri, A, Del Bufalo, D, Caiafa, P & Reale, A 2015, 'PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression', Oncotarget, vol. 6, no. 17, pp. 15008-15021.
Mariano G, Ricciardi MR, Trisciuoglio D, Zampieri M, Ciccarone F, Guastafierro T et al. PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression. Oncotarget. 2015;6(17):15008-15021.
Mariano, Germano ; Ricciardi, Maria Rosaria ; Trisciuoglio, Daniela ; Zampieri, Michele ; Ciccarone, Fabio ; Guastafierro, Tiziana ; Calabrese, Roberta ; Valentini, Elisabetta ; Tafuri, Agostino ; Del Bufalo, Donatella ; Caiafa, Paola ; Reale, Anna. / PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression. In: Oncotarget. 2015 ; Vol. 6, No. 17. pp. 15008-15021.
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