https://orcid.org/0000-0001-7802-5564
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.
#Anticancer #MetalComplexes #OvarianCarcinoma
Graphical Abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Author contributions
Conceptualization: P Štarha and A Mrkvicová; data curation: I Nemec, R Křikavová, P Štarha and A Mrkvicová; formal analysis: I Nemec, P Štarha and A Mrkvicová; funding acquisition: P Štarha; investigation: I Nemec, P Štarha, E Peterová, R Havelek, D Muthná and A Mrkvicová; methodology: P Štarha, D Muthná, E Peterová and P Kazimírová; project administration: P Štarha, E Peterová and A Mrkvicová; resources: P Štarha; supervision: P Štarha and A Mrkvicová; validation: I Nemec and P Štarha; visualization: P Štarha and A Mrkvicová; writing original draft: R Křikavová, I Nemec, P Štarha and A Mrkvicová; writing, review and editing: R Křikavová, P Štarha, A Mrkvicová and M Řezáčová.
Acknowledgments
The authors thank Pavla Richterová for performing elemental analyses and Lukáš Masaryk for help with the synthesis of some compounds and for performing some NMR experiments.
Financial & competing interests disclosure
This work was supported by the Czech Health Research Council of the Ministry of Health of the Czech Republic (AZV project NU22-08-00236), by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601) and by Palacký University Olomouc (projects IGA_PrF_2020_016, IGA_PrF_2021_009 and IGA_PrF_2022_006). This work was also supported by the Cooperation Program, research area DIAG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.