Non apoptotic programmed cell death induced by a phosphine copper(I) complex as a new tool for overcoming cisplatin and multi drug resistence

A lot of efforts have been directed over last years towards R&D of new metal-based anticancer drugs. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. In this field, various hydrophilic "CuP4" complexes have been recently synthesized and [Cu(thp)4]PF6 has been shown to be more potent than cisplatin against different human tumour cells. Chemosensitivity tests suggested that [Cu(thp)4]PF6 besides not being potential MDR substrate, acted through a different mechanism of action than cisplatin. Cytological stains and FACS analyses indicated that [Cu(thp)4}PF6 inhibited cell growth via G2/M cell cycle arrest and extensive cellular vacuolization accompanied with the loss of mitochondrial transmembrane potential and polyubiquitinated protein accumulation