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Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells
Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 3410, p 3410 (2021), International Journal of Molecular Sciences, Volume 22, Issue 7
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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 damage-inducing 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.
- Subjects :
- 0301 basic medicine
medicine.disease_cause
Epigenesis, Genetic
Histones
lcsh:Chemistry
0302 clinical medicine
Settore BIO/06 - Anatomia Comparata E Citologia
lcsh:QH301-705.5
Spectroscopy
Epigenomics
DNA methylation
biology
Chemistry
General Medicine
3. Good health
Computer Science Applications
carbazole derivative
Histone
030220 oncology & carcinogenesis
MCF-7 Cells
Female
epigenetic
Signal Transduction
Carbazoles
Antineoplastic Agents
Breast Neoplasms
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
breast cancer
medicine
Humans
Epigenetics
Physical and Theoretical Chemistry
Molecular Biology
epigenetics
Organic Chemistry
genomic instability
Comet assay
Settore BIO/18 - Genetica
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
MCF-7
carbazole derivatives
Cancer cell
biology.protein
Cancer research
Tumor Suppressor Protein p53
Genotoxicity
DNA Damage
Mutagens
Subjects
Details
- ISSN :
- 14220067 and 16616596
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....42d31c6f019e685c32e3146ea342d8ef
- Full Text :
- https://doi.org/10.3390/ijms22073410