Genotoxicity and epigenotoxicity of carbazole-derived molecules on mcf-7 breast cancer cells

Luparello, Claudio, Cruciata, Ilenia, Joerger, Andreas C, Ocasio, Cory A, Jones, Rhiannon, Tareque, Raysa Khan, Bagley, Mark C, Spencer, John, Walker, Martin, Austin, Carol, Ferrara, Tiziana, D′Oca, Pietro, Bellina, Rossella, Branni, Rossella and Caradonna, Fabio (2021) Genotoxicity and epigenotoxicity of carbazole-derived molecules on mcf-7 breast cancer cells. International Journal of Molecular Sciences, 22 (7). a3410 1-14. ISSN 1661-6596

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Abstract

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily primed PCR to analyze their intrinsic DNA damageinducing and DNA methylation-changing abilities. We demonstrate that small modifications in the substitution patterns of carbazoles can have profound effects on their intrinsic genotoxic and epigenetic properties, with PK9320 and PK9323 being eligible candidates as “anticancer compounds” and “anticancer epi-compounds” and PK083 a “damage-corrective” compound on human breast adenocarcinoma cells. Such different properties may be exploited for their use as anticancer agents and chemical probes.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 12 Apr 2021 08:29
Last Modified: 12 Apr 2021 08:30
URI: http://sro.sussex.ac.uk/id/eprint/98383

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