Rh(III) and Ru(II) complexes with phosphanyl-alkylamines: inhibition of DNA synthesis induced by anticancer Rh complex
Abstract
Aim: This investigation was designed to synthesize half-sandwich Rh(III) and Ru(II) complexes and study their antiproliferative activity in human cancer cell lines. Materials & methods: Nine compounds were prepared and tested by various assays for their anticancer activity and mechanism of action.
Results: Hit Rh(III) complex 6 showed low-micromolar potency in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian carcinoma cell lines, promising selectivity toward these cancer cells over normal lung fibroblasts and an unprecedented mechanism of action in the treated cells. DNA synthesis was decreased and CDKN1A expression was upregulated, but p21 expression was not induced.
Conclusion: Rh complex 6 showed high antiproliferative activity, which is induced through a p21-independent mechanism of action. Plain language summary: Nine rhodium(III)and ruthenium(II) complexes were developed and screened for their anticancer activity on a panel of human cancer cell lines.
The best-performing rhodium(III) complex (6) showed high activity in ovarian cancer cells, including the variant resistant to the conventional anticancer drug cisplatin, while it was less effective towards non-cancerous lung fibroblasts. In cancer cells, compound 6 induced a modification of the cell cycle connected with a significant decrease in DNA synthesis, which was not observed for cisplatin.
The effect of 6 on the expression of proteins related to the cell cycle modification was analysed by quantitative PCR and western blot in cancer cells and the results indicated a p21-independent mode of anticancer action, which is different from cisplatin. Tweetable abstract: Half-sandwich Rh(III) complexes showed low-micromolar potency in cisplatin-sensitive and -resistant ovarian carcinoma cell lines (A2780, A2780cis) induced through a DNA synthesis decrease and a p21-independent cell death. [GRAPHICS] .