Potent in vitro and in vivo anticancer activity of new bipyridine and bipyrimidine gold (III) dithiocarbamate derivatives

Muhammad Altaf, Naike Casagrande, Elena Mariotto, Nadeem Baig, Abdel Nasser Kawde, Giuseppe Corona, Roberto Larcher, Cinzia Borghese, Claudia Pavan, Adam A. Seliman, Donatella Aldinucci, Anvarhusein A. Isab

Research output: Contribution to journalArticle

Abstract

We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1–C8)and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au2(BPM)(DMDTC)2]Cl4) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.

Original languageEnglish
Article number474
Number of pages14
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 2019

Keywords

  • Anticancer therapy
  • Cisplatin resistance
  • Doxorubicin resistance
  • Gold (III) complexes
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Altaf, M., Casagrande, N., Mariotto, E., Baig, N., Kawde, A. N., Corona, G., Larcher, R., Borghese, C., Pavan, C., Seliman, A. A., Aldinucci, D., & Isab, A. A. (2019). Potent in vitro and in vivo anticancer activity of new bipyridine and bipyrimidine gold (III) dithiocarbamate derivatives. Cancers, 11(4), [474]. https://doi.org/10.3390/cancers11040474