The elimination of tumor cells by apoptosis is the main mechanism of action of chemotherapeutic drugs. More recently, autophagic cell death has been shown to trigger a nonapoptotic cell death program in cancer cells displaying functional defects of caspases. Fenretinide (FenR), a synthetic derivative of retinoic acid, promotes growth inhibition and induces apoptosis in a wide range of tumor cell types. The present study was designed to evaluate the ability of fenretinide to induce caspase-independent cell death and to this aim we used the human mammary carcinoma cell line MCF-7, lacking functional caspase-3 activity. We demonstrated that in these cells fenretinide is able to trigger an autophagic cell death pathway. In particular we found that fenretinide treatment resulted in the increase in Beclin 1 expression, the conversion of the soluble form of LC3 to the autophagic vesicle-associated form LC3-II and its shift from diffuse to punctate staining and finally the increase in lysosomes/autophagosomes. By contrast, caspase-3 reconstituted MCF-7 cell line showed apoptotic cell death features in response to fenretinide treatment. These data strongly suggest that fenretinide does not invariably elicit an apoptotic response but it is able to induce autophagy when apoptotic pathway is deregulated. The understanding of the molecular mechanisms involved in fenretinide action is important for the future design of therapies employing this retinoid in breast cancer treatment.

Fazi, B., Bursch, W., Fimia, G., Nardacci, R., Piacentini, M., DI SANO, F., et al. (2008). Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. AUTOPHAGY, 4(4), 435-441.

Fenretinide induces autophagic cell death in caspase-defective breast cancer cells

FAZI, BARBARA;PIACENTINI, MAURO;DI SANO, FEDERICA;PIREDDA, LUCIA
2008-05-01

Abstract

The elimination of tumor cells by apoptosis is the main mechanism of action of chemotherapeutic drugs. More recently, autophagic cell death has been shown to trigger a nonapoptotic cell death program in cancer cells displaying functional defects of caspases. Fenretinide (FenR), a synthetic derivative of retinoic acid, promotes growth inhibition and induces apoptosis in a wide range of tumor cell types. The present study was designed to evaluate the ability of fenretinide to induce caspase-independent cell death and to this aim we used the human mammary carcinoma cell line MCF-7, lacking functional caspase-3 activity. We demonstrated that in these cells fenretinide is able to trigger an autophagic cell death pathway. In particular we found that fenretinide treatment resulted in the increase in Beclin 1 expression, the conversion of the soluble form of LC3 to the autophagic vesicle-associated form LC3-II and its shift from diffuse to punctate staining and finally the increase in lysosomes/autophagosomes. By contrast, caspase-3 reconstituted MCF-7 cell line showed apoptotic cell death features in response to fenretinide treatment. These data strongly suggest that fenretinide does not invariably elicit an apoptotic response but it is able to induce autophagy when apoptotic pathway is deregulated. The understanding of the molecular mechanisms involved in fenretinide action is important for the future design of therapies employing this retinoid in breast cancer treatment.
mag-2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Animals; Antineoplastic Agents; Autophagy; Humans; Apoptosis Regulatory Proteins; Caspase 3; Breast Neoplasms; Cell Line, Tumor; Membrane Proteins; Rats; Fenretinide; Female; Signal Transduction
http://www.landesbioscience.com/journals/autophagy/FaziAUTO4-4.pdf
Fazi, B., Bursch, W., Fimia, G., Nardacci, R., Piacentini, M., DI SANO, F., et al. (2008). Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. AUTOPHAGY, 4(4), 435-441.
Fazi, B; Bursch, W; Fimia, G; Nardacci, R; Piacentini, M; DI SANO, F; Piredda, L
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Autophagy.pdf

solo utenti autorizzati

Descrizione: articolo principale
Licenza: Copyright dell'editore
Dimensione 466.58 kB
Formato Adobe PDF
466.58 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/2108/29422
Citazioni
  • ???jsp.display-item.citation.pmc??? 25
  • Scopus 61
  • ???jsp.display-item.citation.isi??? ND
social impact