Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence.

Celeste Caruso Bavisotto, Marianna Lauricella, Rosario Barone, Giovanni Zummo, Claudia Campanella, Antonella Marino Gammazza, Francesco Carini, Antonella D'Anneo, Valentina Di Felice, Claudia Campanella, Antonella Marino Gammazza, Rosario Barone, Magdalena Gorska, Celeste Caruso Bavisotto, Magdalena Gorska, Francesco Cappello, Everly Conway De Macario, Alberto J.L. Macario, Michal Wozniak, Valentina Di FeliceFrancesco Cappello

Risultato della ricerca: Article

28 Citazioni (Scopus)

Abstract

The chaperone Hsp60 is pro-carcinogenic in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not yet known whether doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of Hsp60. We found a doxorubicin dose-dependent viability reduction in a human lung mucoepidermoid cell line that was paralleled by the appearance of cell senescence markers. Concomitantly, intracellular Hsp60 levels decreased while its acetylation levels increased. The data suggest that Hsp60 acetylation interferes with the formation of the Hsp60/p53 complex and/or promote its dissociation, both causing an increase in the levels of free p53, which can then activate the p53-dependent pathway toward cell senescence. On the other hand, acetylated Hsp60 is ubiquitinated and degraded and, thus, the anti-apoptotic effect of the chaperonin is abolished with subsequent tumor cell death. Our findings could help in the elucidation of the molecular mechanisms by which doxorubicin counteracts carcinogenesis and, consequently, it would open new roads for the development of cancer treatment protocols targeting Hsp60.
Lingua originaleEnglish
pagine (da-a)75-86
Numero di pagine12
RivistaCancer Letters
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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