Although paclitaxel (Taxol) is an active chemotherapeutic agent for the treatment of breast cancer, not all breast tumors are sensitive to this drug. In particular, there is a wide agreement on the low sensitivity of estrogen receptor (ER) α-positive breast cancer to paclitaxel treatment. However, the ERα-based insensitivity to paclitaxel is still elusive. Here, the effect of the E2/ERα-dependent upregulation of neuroglobin (NGB), an antiapoptotic globin, on the reduced sensitivity of breast cancer cells to paclitaxel-induced apoptosis has been evaluated in ERα-containing MCF-7 cells. The E2 pretreatment enhances the ERα activity and significantly impairs paclitaxel-induced apoptosis as evaluated by Annexin V assay and PARP-1 cleavage. NGB displays a pivotal role in the E2/ERα-induced antiapoptotic pathway to abrogate paclitaxel-induced cell death in stable NGB-silenced MCF-7 cell clones. Moreover, in the absence of the active ERα, paclitaxel significantly reduces the NGB cell content. In conclusion, these results highlight the involvement of ERα activation and of E2/ERα-dependent NGB upregulation in the insensitivity of MCF-7 to paclitaxel. These novel findings could have important implications in the development of targeted therapeutics for overcoming paclitaxel insensitivity in ERα-positive human breast cancer

Fiocchetti, M., Cipolletti, M., Leone, S., Ascenzi, P., Marino, M. (2016). Neuroglobin overexpression induced by the 17β-Estradiol-Estrogen receptor-α Pathway reduces the sensitivity of MCF-7 Breast cancer cell to paclitaxel. IUBMB LIFE, 68(8), 645-651 [10.1002/iub.1522].

Neuroglobin overexpression induced by the 17β-Estradiol-Estrogen receptor-α Pathway reduces the sensitivity of MCF-7 Breast cancer cell to paclitaxel

FIOCCHETTI, MARCO;CIPOLLETTI, MANUELA;LEONE, STEFANO;ASCENZI, Paolo;MARINO, Maria
2016

Abstract

Although paclitaxel (Taxol) is an active chemotherapeutic agent for the treatment of breast cancer, not all breast tumors are sensitive to this drug. In particular, there is a wide agreement on the low sensitivity of estrogen receptor (ER) α-positive breast cancer to paclitaxel treatment. However, the ERα-based insensitivity to paclitaxel is still elusive. Here, the effect of the E2/ERα-dependent upregulation of neuroglobin (NGB), an antiapoptotic globin, on the reduced sensitivity of breast cancer cells to paclitaxel-induced apoptosis has been evaluated in ERα-containing MCF-7 cells. The E2 pretreatment enhances the ERα activity and significantly impairs paclitaxel-induced apoptosis as evaluated by Annexin V assay and PARP-1 cleavage. NGB displays a pivotal role in the E2/ERα-induced antiapoptotic pathway to abrogate paclitaxel-induced cell death in stable NGB-silenced MCF-7 cell clones. Moreover, in the absence of the active ERα, paclitaxel significantly reduces the NGB cell content. In conclusion, these results highlight the involvement of ERα activation and of E2/ERα-dependent NGB upregulation in the insensitivity of MCF-7 to paclitaxel. These novel findings could have important implications in the development of targeted therapeutics for overcoming paclitaxel insensitivity in ERα-positive human breast cancer
Fiocchetti, M., Cipolletti, M., Leone, S., Ascenzi, P., Marino, M. (2016). Neuroglobin overexpression induced by the 17β-Estradiol-Estrogen receptor-α Pathway reduces the sensitivity of MCF-7 Breast cancer cell to paclitaxel. IUBMB LIFE, 68(8), 645-651 [10.1002/iub.1522].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/304410
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 20
social impact