1. In vitro and in vivo studies of gold(I) azolate/phosphane complexes for the treatment of basal like breast cancer
- Author
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Manuela Iezzi, Eunice Wairimu Maina, Cristina Marchini, Stefania Pucciarelli, Guojun Wu, Augusto Amici, Junbiao Wang, Caterina Bartolacci, Valentina Gambini, Anna Teresa Ramadori, Stefano Ferraro, Martina Tilio, Q. Ping Dou, Oumarou Camille Simon, Cristina Andreani, and Rossana Galassi
- Subjects
0301 basic medicine ,Azoles ,Cell Survival ,Phosphines ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Breast cancer ,Gold Compounds ,In vivo ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Cell Proliferation ,Pharmacology ,Cisplatin ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Cell growth ,Organic Chemistry ,Cancer ,General Medicine ,medicine.disease ,In vitro ,030104 developmental biology ,Mechanism of action ,030220 oncology & carcinogenesis ,Cancer research ,medicine.symptom ,Drug Screening Assays, Antitumor ,Organogold Compounds ,medicine.drug - Abstract
Basal like breast cancer (BLBC) is a very aggressive subtype of breast cancer giving few chances of survival, against which cisplatin based therapy is a compromise among the anticancer activity, the resistance development and the severe side effects. With the aim of finding new anticancer agents alternative to cisplatin, seven gold(I) azolate/phosphane compounds were evaluated in vitro by MTT tests in human MDA-MB-231, human mammary epithelial HMLE cells overexpressing FoxQ1, and murine A17 cells as models of BLBC. Two compounds, (4,5-dichloro-1H-imidazolate-1-yl)-(triphenylphosphane)-gold(I) 1 and (4,5-dicyano-1H-imidazolate-1-yl)-(triphenylphosphane)-gold(I) 2 were found very active and chosen for an in vivo study in A17 tumors transplanted in syngeneic mice. The compounds resulted to be more active than cisplatin, less nephrotoxic and generally more tolerated by the mice. This study also provides evidence that both gold(I) complexes inhibited the 19 S proteasome-associated deubiquitinase USP14 and induced apoptosis, while compound 1's mechanism of action depends also on its ability to down-regulate key molecules governing cancer growth and progression, such as STAT3 and Cox-2.
- Published
- 2018