4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells
dc.creator | Rodrigues, Bruna dos Santos | |
dc.creator | Marcelino, Renato Ivan de Ávila | |
dc.creator | Miranda, Polyana Lopes Benfica | |
dc.creator | Pires, Ludmila Bringel | |
dc.creator | Oliveira, Cecilia Maria Alves de | |
dc.creator | Vandresen, Fábio | |
dc.creator | Silva, Cleuza Conceição da | |
dc.creator | Valadares, Marize Campos | |
dc.date.accessioned | 2023-09-05T10:31:18Z | |
dc.date.available | 2023-09-05T10:31:18Z | |
dc.date.issued | 2018 | |
dc.description.abstract | Aims: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde-N(4)-{1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells. Main methods: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry. Parameters of toxicity of 4-FTSC was conducted by the investigation of its potential myelotoxicity and lymphotoxicity, hemolytic activity and acute oral toxicity profile. Key findings: 4-FTSC showed promising cytotoxic effects against PC-3 cells (IC50 = 18.46 μM). It also triggered apoptotic morphological changes, phosphatidylserine externalization and a significant increase of DNA fragmentation in PC-3 cells. Moreover, 4-FTSC did not show changes in the PC-3 cell cycle with levels of p21, p27, NFĸB and cyclin D1 similar to those found in both control and treated cells. 4-FTSC also promoted an increase of p53 levels associated with mitochondrial impairment through loss of ∆Ψm and ROS overproduction. 4-FTSC-induced cell death mechanism in PC-3 cells involved activation of caspase-3/-7 through apoptosis intrinsic pathway via caspase-9. Regarding toxicological profile, 4-FTSC showed in vitro lymphotoxicity, although with low cytotoxicity for bone marrow progenitors and no hemolytic potential. Moreover, it was classified as GHS category 5 (LD50 > 2000–5000 mg/Kg), suggesting it has low acute oral systemic toxicity. Significance: 4-FTSC seems to be a promising candidate to be used as a clinical tool in prostate cancer treatment. Further studies are required to better clarify its toxicopharmacological effects found in this compound. | pt_BR |
dc.identifier.citation | RODRIGUES, Bruna dos Santos et al. 4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells. Life Sciences, Amsterdam, v. 203, p. 141-149, 2018. DOI: 10.1016/j.lfs.2018.04.024. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0024320518302054?via%3Dihub. Acesso em: 28 ago. 2023. | pt_BR |
dc.identifier.doi | 10.1016/j.lfs.2018.04.024 | |
dc.identifier.issn | e- 1879-0631 | |
dc.identifier.issn | 0024-3205 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/abs/pii/S0024320518302054?via%3Dihub | |
dc.language.iso | eng | pt_BR |
dc.publisher.country | Holanda | pt_BR |
dc.publisher.department | Instituto de Química - IQ (RMG) | pt_BR |
dc.rights | Acesso Restrito | pt_BR |
dc.subject | Thiosemicarbazone | pt_BR |
dc.subject | Limonene | pt_BR |
dc.subject | Apoptosis | pt_BR |
dc.subject | Prostate cancer | pt_BR |
dc.title | 4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells | pt_BR |
dc.type | Artigo | pt_BR |
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