An Erlotinib gold(I) conjugate for combating triple-negative breast cancer

• Published in: Journal of inorganic biochemistry Vol. 203; p. 110910
• Main Authors: Ortega, Enrique, Zamora, Ana, Basu, Uttara, Lippmann, Petra, Rodríguez, Venancio, Janiak, Christoph, Ott, Ingo, Ruiz, José
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - toxicity; Apoptosis; Apotosis; Breast cancer; Cell Proliferation - drug effects; DNA Damage; Erlotinib; Erlotinib Hydrochloride - analogs & derivatives; Gold - chemistry; Gold(I) conjugate complex; HT29 Cells; Humans; MCF-7 Cells; Organogold Compounds - chemical synthesis; Organogold Compounds - toxicity; Reactive oxygen species; Reactive Oxygen Species - metabolism; Triple Negative Breast Neoplasms - metabolism; Gold(I) conjugate complex; Reactive oxygen species; Breast cancer; Erlotinib; Apotosis; DNA damage
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2019.110910

An Erlotinib triphenylphosphane gold(I) conjugate has been prepared from AuCl(PPh3) and its crystal structure has been established by X-ray diffraction, showing a metallo-helicate formation. IC50 values of the new gold conjugate were calculated towards a panel of human tumor cell lines representative of breast (MCF-7, MDA-MB-231) and colon (HT-29) cancer cells. Overall, the gold conjugate exhibited higher cytotoxic activity than that of Erlotinib against the cancer cells studied. Particularly, the antiproliferative effect of the conjugate demonstrated to be 68-fold higher than Erlotinib in highly metastatic and triple negative MDA-MB-231 cell line. The gold conjugate caused DNA damage, reactive oxygen species (ROS) increase and induced apoptosis. Flow cytometry analysis showed that the conjugate induces significant arrest in S and G2/M phases primarily, whereas Erlotinib, as an inhibitor of epidermal growth factor receptor (EGFR), blocks G1/S transition and increases G1 cell population. A novel Erlotinib triphenylphosphane gold(I) conjugate is highly active in triple negative MDA-MB-231 cell line, causing DNA damage, Reactive oxygen species (ROS) increase and inducing apoptosis. [Display omitted] •A novel Erlotinib triphenylphosphane gold(I) conjugate has been synthesized.•The crystal structure of the gold(I) complex has been determined.•The gold(I) complex inhibits the growth of metastatic MDA-MB-231 cells.•The conjugate induces significant arrest in S and G2/M phases primarily.•The conjugate caused DNA damage and reactive oxygen species increase.