Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives
We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (<b>C1</b>–<b>C8)</b> 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), ova...
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doaj-47901cc90fda4dd59e7825faa6c65df12020-11-25T00:50:03ZengMDPI AGCancers2072-66942019-04-0111447410.3390/cancers11040474cancers11040474Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate DerivativesMuhammad Altaf0Naike Casagrande1Elena Mariotto2Nadeem Baig3Abdel-Nasser Kawde4Giuseppe Corona5Roberto Larcher6Cinzia Borghese7Claudia Pavan8Adam A. Seliman9Donatella Aldinucci10Anvarhusein A. Isab11Department of Chemistry, GC University, Lahore 54000, PakistanMolecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyMolecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyDepartment of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi ArabiaDepartment of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi ArabiaImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyCenter for Technological Transfer, Edmund Mach Foundation, 38010 Trento, ItalyMolecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyMolecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyLab Technical Support Office (LTSO), King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi ArabiaMolecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyDepartment of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi ArabiaWe synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (<b>C1</b>–<b>C8)</b> 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 <b>C2</b>, <b>C3</b>, <b>C6</b>, and <b>C7</b> 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 <b>C6</b> ([Au<sub>2</sub>(BPM)(DMDTC)<sub>2</sub>]Cl<sub>4</sub>) 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, <b>C6</b> 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 <b>C6</b> as a new agent for prostate cancer treatment.https://www.mdpi.com/2072-6694/11/4/474gold (III) complexesanticancer therapycisplatin resistancedoxorubicin resistanceprostate cancer |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives Cancers gold (III) complexes anticancer therapy cisplatin resistance doxorubicin resistance prostate cancer |
author_facet |
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 |
author_sort |
Muhammad Altaf |
title |
Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives |
title_short |
Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives |
title_full |
Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives |
title_fullStr |
Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives |
title_full_unstemmed |
Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives |
title_sort |
potent in vitro and in vivo anticancer activity of new bipyridine and bipyrimidine gold (iii) dithiocarbamate derivatives |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-04-01 |
description |
We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (<b>C1</b>–<b>C8)</b> 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 <b>C2</b>, <b>C3</b>, <b>C6</b>, and <b>C7</b> 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 <b>C6</b> ([Au<sub>2</sub>(BPM)(DMDTC)<sub>2</sub>]Cl<sub>4</sub>) 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, <b>C6</b> 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 <b>C6</b> as a new agent for prostate cancer treatment. |
topic |
gold (III) complexes anticancer therapy cisplatin resistance doxorubicin resistance prostate cancer |
url |
https://www.mdpi.com/2072-6694/11/4/474 |
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