A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis possible role of miRNA-125a-5p and miRNA-181a-5p
| Autor: | Bassam Badran, Hussein Fayyad-Kazan, Eva Hamade, Rabih S. Talhouk, Mohammad Fayyad-Kazan, Rawan Makki, Ali Hachem, René Grée, Rania El Majzoub, Assaad Nasr El Dine |
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| Přispěvatelé: | Lebanese University [Beirut] (LU), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), American University of Beirut [Beyrouth] (AUB), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Thiosemicarbazones
0106 biological sciences 0301 basic medicine Poly ADP ribose polymerase Triple Negative Breast Neoplasms Apoptosis Biology 01 natural sciences Biochemistry 03 medical and health sciences Breast cancer Thiosemicarbazone derivatives Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols microRNA Genetics medicine Humans [CHIM]Chemical Sciences MTT assay Viability assay Receptor 3' Untranslated Regions Molecular Biology Triple-negative breast cancer medicine.disease 3. Good health MicroRNAs 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 miRNAs Cancer research Cisplatin 010606 plant biology & botany |
| Zdroj: | Genes and Genomics Genes and Genomics, 2019, 41 (12), pp.1431-1443. ⟨10.1007/s13258-019-00866-y⟩ |
| ISSN: | 2092-9293 1976-9571 |
| DOI: | 10.1007/s13258-019-00866-y⟩ |
| Popis: | International audience; Background - Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immunotherapy. In an attempt to identify potent and selective anti-TNBC agents, a set of thiosemicarbazone derivatives were screened for their cytotoxic activity against MDA-MB 231 breast cancer cell line. Methods - MTT assay was used to examine cell viability. P53 phosphorylation status, poly (ADP-ribose) polymerase (PARP) cleavage as well as Bcl2 and Bax protein levels were assessed by Western blot. Quantitative Real Time-PCR was carried out to characterize miRNAs expression levels. Results - Combining Cisplatin + thiosemicarbazone compound 4 showed potent anti-TNBC potential. Cisplatin + compound 4 significantly enhanced p53 phosphorylation, induced Bax amount, reduced Bcl2 protein levels, enhanced PARP cleavage and modulated miRNAs expression profile in TNBCs, with a particular overexpression of miR-125a-5p and miR-181a-5p. Intriguingly, miR-125a-5p and miR-181a-5p could significantly downregulate BCL2 expression by binding to their target sites in the 3'UTR. Conclusions - Collectively, our results demonstrate an anti-TNBC activity of Cisplatin + thiosemicarbazone compound 4 combination mediated via induction of apoptosis. |
| Databáze: | OpenAIRE |
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