A new platinum(II) compound anticancer drug candidate with selective cytotoxicity for breast cancer cells

Abstract

[Pt(O,O'-acac)(gamma-acac)(DMS)] (PtAcD) is able to induce apoptosis in various human cancer cells, including the cisplatin-resistant human breast carcinoma MCF-7 cells. Here, to confirm that PtAcD has the potentiality for therapeutic intervention, we studied its effects in primary cultured epithelial breast cells obtained from cancers and also from the corresponding histologically proven non-malignant tissue adjacent to the tumor. We demonstrated that PtAcD (1) is more cytotoxic in cancer than in normal breast cells; (2) activated NAD(P)H oxidase, leading to PKC-zeta and PKC-alpha tanslocations; (3) activated antiapoptotic pathways based on the PKC-alpha, ERK1/2 and Akt kinases; (4) activated PKC-zeta and, only in cancer cell PKC-delta, responsible for the sustained phosphorylation of p38 and JNK1/2, kinases both of which are involved in the mitochondrial apoptotic process. Moreover, crosstalk between ERK/Akt and JNK/p38 pathways affected cell death and survival in PtAcD-treated breast cell. In conclusion, this study adds and extends data that highlight the pharmacological potential of PtAcD as an anti breast cancer drug.


Tutti gli autori

  • A. Muscella , C. Vetrugno , F. P. Fanizzi , C. Manca , S. A. De Pascali , S. Marsigliante

Titolo volume/Rivista

CELL DEATH & DISEASE


Anno di pubblicazione

2013

ISSN

2041-4889

ISBN

Non Disponibile


Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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