Abstract
| Lingua originale | English |
|---|---|
| pagine (da-a) | 1877-1888 |
| Numero di pagine | 12 |
| Rivista | Cell Death and Differentiation |
| Volume | 21 |
| Stato di pubblicazione | Published - 2014 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
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Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer. / Stassi, Giorgio; Todaro, Matilde; Apuzzo, Tiziana; Eramo, Adriana; Zeuner, Ann; Biffoni, Mauro; De Maria, Ruggero; Sette; Francescangeli, Federica; Zapparelli, Giuseppina; Contavalli; Baiocchi; De Angelis.
In: Cell Death and Differentiation, Vol. 21, 2014, pag. 1877-1888.Risultato della ricerca: Article
}
TY - JOUR
T1 - Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer
AU - Stassi, Giorgio
AU - Todaro, Matilde
AU - Apuzzo, Tiziana
AU - Eramo, Adriana
AU - Zeuner, Ann
AU - Biffoni, Mauro
AU - De Maria, Ruggero
AU - Sette, null
AU - Francescangeli, Federica
AU - Zapparelli, Giuseppina
AU - Contavalli, null
AU - Baiocchi, null
AU - De Angelis, null
PY - 2014
Y1 - 2014
N2 - Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC
AB - Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC
UR - http://hdl.handle.net/10447/163835
M3 - Article
VL - 21
SP - 1877
EP - 1888
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
ER -