Substituted diaryl diselenides: cytotoxic and apoptotic effect in human colon adenocarcinoma cells
Fernanda Nedel1, Vinicius F Campos, Diego Alves
1Grupo de Oncologia Celular e Molecular, Programa de Pós-Graduação em Biotecnologia, Centro de Desenvolvimento Tecnológico/Biotecnologia, Universidade Federal de Pelotas, Capão do Leão, RS 96010-900, Brazil.
Aims:
To investigate the effects and study the underlying cell death mechanisms of diaryl diselenides, including: diphenyl diselenide (C(6)H(5)Se)(2); 4-chlorodiphenyl diselenide (4-ClC(6)H(4)Se)(2); 3-(trifluoromethyl)-diphenyl diselenide (3-CF(3)C(6)H(4)Se)(2) and 4-methoxydiphenyl diselenide (4-MeOC(6)H(4)Se)(2), on the human colon adenocarcinoma cell line HT-29.
Main Methods:
The viability of HT-29 cells after exposure to the diaryl diselenides and its substituted structures was based on the MTT assay. To verify if cell death was mediated throughout apoptosis mechanisms, flow cytometry and real-time PCR (qPCR) analyses were conducted.
Key Findings:
The MTT assay and flow cytometry analyses showed that (3-CF(3)C(6)H(4)Se)(2) and (4-MeOC(6)H(4)Se)(2) induced cytotoxicity through apoptosis mechanisms in HT-29 cells. qPCR revealed there was an up-regulation of pro-apoptotic (Bax, casapase-9, caspase-8, apoptosis-inducing factor (AIF) and Endonuclease G (EndoG)) and cell-cycle arrest genes (p53 and p21) and down-regulation of anti-apoptotic (Bcl-2 and survivin) and Myc genes.
Significance:
These results demonstrate that (3-CF(3)C(6)H(4)Se)₂ and (4-MeOC(6)H(4)Se)(2) have the potential to induce apoptosis in HT-29 cells through the activation of caspase-dependent and independent pathways and through cell-cycle arrest.
