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Distinct Classes of Flavonoids and Epigallocatechin Gallate, Polyphenol Affects an Oncogenic Mutant p53 Protein, Cell Growth and Invasion in a TNBC Breast Cancer Cell Line
- Source :
- Cells, Volume 10, Issue 4, Cells, Vol 10, Iss 797, p 797 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- Mutant p53(s) are widely considered as oncogenes and promote several gain-of-function oncogenic activities. p53 mutations correlate with higher rates of metastasis and poor survival<br />therefore, it is paramount to inhibit mutant p53 protein either directly or indirectly. Although some compounds have been developed, none of them have achieved a desirable level of specificity. Some of these compounds only targeted specific mutations. In search of less-toxic compounds, we tested plant-derived compounds on mutant p53 triple-negative breast cancer cell lines. Here, we show that the compounds tested reduced the protein levels of one of the more frequent oncogenic p53 mutants (R249S<br />hot spot mutation), and its important targets that promote invasion and metastasis, including GMPS and IMPDH1. All compounds tested perturbed the invasion potential of the breast cancer cell line. These compounds downregulated several nucleotide metabolism genes (NMGs) which are essential for cell cycle progression. We observed S-phase arrest correlating to reduced cell proliferation and increased replication stress. Moreover, we also show a reduction of key ETS transcription family members including ETS2, ETS1, ETV1, and ETV4, which are involved in invasion and metastasis. We propose that these compounds may inhibit invasion by interfering with multiple pathways. Our findings exemplify that these tested compounds could inhibit invasion and cell growth in TNBC in a nucleotide-dependent manner.
- Subjects :
- Transcription, Genetic
DNA damage
replication stress
Mutant
Triple Negative Breast Neoplasms
Biology
medicine.disease_cause
nucleotide metabolism genes
ETV1
Article
Catechin
Metastasis
breast cancer
ETS1
Cell Line, Tumor
medicine
Humans
metastasis
Neoplasm Invasiveness
RNA, Messenger
lcsh:QH301-705.5
Gene
Cell Proliferation
Mutation
Biological Products
gain-of-function
Proto-Oncogene Proteins c-ets
Cell growth
Cell Cycle
mutant p53
Polyphenols
General Medicine
Oncogenes
medicine.disease
polyphenol
lcsh:Biology (General)
flavonoids
Cancer research
Female
Mutant Proteins
Tumor Suppressor Protein p53
TNBC
ETS
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....202cfdc61fb3d52936d4fa41ec2d6d5b
- Full Text :
- https://doi.org/10.3390/cells10040797