Novel L-type chiral metal(II) complexes inhibit breast cancer growth through synergistic effects of anti-angiogenesis, anti-inflammatory, apoptosis induction and cuproptosis

Abstract

Breast cancer ranks first among female malignant tumors and is the largest cancer worldwide. Recently, research on chiral metal-based complexes for cancer treatment has significantly increased. This study synthesized an L-copper(II) complex Cu-1 and a pair of chiral nickel(II) complexes Ni-1 (L-type) and Ni-2 (D-type). The antiproliferative activities of Cu-1, Ni-1, and Ni-2 against female malignant tumor cells (MCF-7, MDA-MB-231, SKOV3, Hela) were evaluated. Among them, the L-type complexes Cu-1 and Ni-1 exhibited superior bioactivity compared to the D-type Ni-2. Further mechanistic studies demonstrated that Cu-1 and Ni-1 could effectively inhibit the growth of MCF-7 cells. Additionally, in vivo experiments in nude mice verified that Cu-1 could exert anti-tumor effects through the synergistic action of multiple pathways. In summary, Cu-1 and Ni-1 possess multiple functions including anti-tumor angiogenesis, anti-inflammatory, apoptosis, and copper-induced death, providing theoretical reference for the development of breast cancer drugs.

Graphical abstract