Synergistic antitumor effect of doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines

Francesca Capone, Eliana Guerriero, Angela Sorice, Giovanni Colonna, Gabriella Storti, Jessica Pagliuca, Giuseppe Castello, Susan Costantini

Research output: Contribution to journalArticle

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Abstract

Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506) has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B) were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i) a strong cell apoptosis induction, (ii) contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii) downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

Original languageEnglish
Article number450390
JournalTheScientificWorldJournal
Volume2014
DOIs
Publication statusPublished - 2014

Fingerprint

apoptosis
Tacrolimus
Doxorubicin
Hepatocellular Carcinoma
Cells
Cell Line
Apoptosis
lissamine rhodamine B
assay
Assays
protein
Bearings (structural)
Cytokines
tumor
Bioassay
bioassay
Annexin A5
cancer
Autophagy
viability

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Medicine(all)

Cite this

Capone, F., Guerriero, E., Sorice, A., Colonna, G., Storti, G., Pagliuca, J., ... Costantini, S. (2014). Synergistic antitumor effect of doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines. TheScientificWorldJournal, 2014, [450390]. https://doi.org/10.1155/2014/450390

Synergistic antitumor effect of doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines. / Capone, Francesca; Guerriero, Eliana; Sorice, Angela; Colonna, Giovanni; Storti, Gabriella; Pagliuca, Jessica; Castello, Giuseppe; Costantini, Susan.

In: TheScientificWorldJournal, Vol. 2014, 450390, 2014.

Research output: Contribution to journalArticle

Capone, F, Guerriero, E, Sorice, A, Colonna, G, Storti, G, Pagliuca, J, Castello, G & Costantini, S 2014, 'Synergistic antitumor effect of doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines', TheScientificWorldJournal, vol. 2014, 450390. https://doi.org/10.1155/2014/450390
Capone, Francesca ; Guerriero, Eliana ; Sorice, Angela ; Colonna, Giovanni ; Storti, Gabriella ; Pagliuca, Jessica ; Castello, Giuseppe ; Costantini, Susan. / Synergistic antitumor effect of doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines. In: TheScientificWorldJournal. 2014 ; Vol. 2014.
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