TY - JOUR
T1 - Chemistry, antiproliferative properties, tumor selectivity, and molecular mechanisms of novel gold(III) compounds for cancer treatment
T2 - A systematic study
AU - Casini, Angela
AU - Kelter, Gerhard
AU - Gabbiani, Chiara
AU - Cinellu, Maria Agostina
AU - Minghetti, Giovanni
AU - Fregona, Dolores
AU - Fiebig, Heinz Herbert
AU - Messori, Luigi
N1 - Funding Information:
Acknowledgments We gratefully acknowledge support from Ente Cassa di Risparmio di Firenze and from the Italian Consortium C.I.R.C.M.S.B. C.G. wishes to thank AIRC for providing her with a Research Fellowship. A.C. thanks the Swiss National Science Foundation for financial support (project number PZ00P2_121933).
PY - 2009
Y1 - 2009
N2 - The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell lines were evaluated in vitro using a systematic screening strategy. Initially all compounds were tested against a panel of 12 human tumor cell lines, and the best performers were tested against a larger 36-cell-line panel. Very pronounced antiproliferative properties were highlighted in most cases, with cytotoxic potencies commonly falling in the low micromolar-and even nanomolar-range. Overall, good-to-excellent tumor selectivity was established for at least seven compounds, making them particularly attractive for further pharmacological evaluation. Compare analysis suggested that the observed antiproliferative effects are caused by a variety of molecular mechanisms, in most cases "DNA-independent," and completely different from those of platinum drugs. Remarkably, some new biomolecular systems such as histone deacetylase, protein kinase C/staurosporine, mammalian target of rapamycin/rapamycin, and cyclin-dependent kinases were proposed for the first time as likely biochemical targets for the gold(III) species investigated. The results conclusively qualify gold(III) compounds as a promising class of cytotoxic agents, of outstanding interest for cancer treatment, while providing initial insight into their modes of action. Graphical Abstract: A series of gold(III) compounds showed cytotoxic properties and tumor selectivity toward a panel of cancer cell lines. Compare analysis provided insight into their possible mechanisms of action.
AB - The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell lines were evaluated in vitro using a systematic screening strategy. Initially all compounds were tested against a panel of 12 human tumor cell lines, and the best performers were tested against a larger 36-cell-line panel. Very pronounced antiproliferative properties were highlighted in most cases, with cytotoxic potencies commonly falling in the low micromolar-and even nanomolar-range. Overall, good-to-excellent tumor selectivity was established for at least seven compounds, making them particularly attractive for further pharmacological evaluation. Compare analysis suggested that the observed antiproliferative effects are caused by a variety of molecular mechanisms, in most cases "DNA-independent," and completely different from those of platinum drugs. Remarkably, some new biomolecular systems such as histone deacetylase, protein kinase C/staurosporine, mammalian target of rapamycin/rapamycin, and cyclin-dependent kinases were proposed for the first time as likely biochemical targets for the gold(III) species investigated. The results conclusively qualify gold(III) compounds as a promising class of cytotoxic agents, of outstanding interest for cancer treatment, while providing initial insight into their modes of action. Graphical Abstract: A series of gold(III) compounds showed cytotoxic properties and tumor selectivity toward a panel of cancer cell lines. Compare analysis provided insight into their possible mechanisms of action.
KW - Anticancer drug
KW - Structure-function relationship
UR - http://www.scopus.com/inward/record.url?scp=70349561362&partnerID=8YFLogxK
U2 - 10.1007/s00775-009-0558-9
DO - 10.1007/s00775-009-0558-9
M3 - Article
C2 - 19543922
AN - SCOPUS:70349561362
SN - 0949-8257
VL - 14
SP - 1139
EP - 1149
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 7
ER -