4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells

Rodrigues, Bruna dos Santos; Marcelino, Renato Ivan de Ávila; Miranda, Polyana Lopes Benfica; Pires, Ludmila Bringel; Oliveira, Cecilia Maria Alves de; Vandresen, Fábio; Silva, Cleuza Conceição da; Valadares, Marize Campos

4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells

Data

2018

Autores

Rodrigues, Bruna dos Santos

Marcelino, Renato Ivan de Ávila

Miranda, Polyana Lopes Benfica

Pires, Ludmila Bringel

Oliveira, Cecilia Maria Alves de

Vandresen, Fábio

Silva, Cleuza Conceição da

Valadares, Marize Campos

Resumo

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.

Palavras-chave

Thiosemicarbazone, Limonene, Apoptosis, Prostate cancer

Citação

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.