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 language | English |
|---|---|
| Pages (from-to) | 15008-15021 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 6 |
| Issue number | 17 |
| Publication status | Published - 2015 |
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Keywords
- Breast cancer
- Chemoresistance
- PARP inhibitors
- Snail
ASJC Scopus subject areas
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression
AU - Mariano, Germano
AU - Ricciardi, Maria Rosaria
AU - Trisciuoglio, Daniela
AU - Zampieri, Michele
AU - Ciccarone, Fabio
AU - Guastafierro, Tiziana
AU - Calabrese, Roberta
AU - Valentini, Elisabetta
AU - Tafuri, Agostino
AU - Del Bufalo, Donatella
AU - Caiafa, Paola
AU - Reale, Anna
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Chemoresistance
KW - PARP inhibitors
KW - Snail
UR - http://www.scopus.com/inward/record.url?scp=84934270574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84934270574&partnerID=8YFLogxK
M3 - Article
VL - 6
SP - 15008
EP - 15021
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 17
ER -