| Registro completo |
| Provedor de dados: |
J. Venom. Anim. Toxins incl. Trop. Dis.
|
| País: |
Brazil
|
| Título: |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells
|
| Autores: |
Machado,Ana Rita Thomazela
Aissa,Alexandre Ferro
Ribeiro,Diego Luis
Ferreira Jr.,Rui Seabra
Sampaio,Suely Vilela
Antunes,Lusânia Maria Greggi
|
| Data: |
2019-01-01
|
| Ano: |
2019
|
| Palavras-chave: |
Snake venom
Epigenetics
GADD45A
CCND1
CDKN1A
|
| Resumo: |
Abstract Background: The use of animal venoms and their toxins as material sources for biotechnological applications has received much attention from the pharmaceutical industry. L-amino acid oxidases from snake venoms (SV-LAAOs) have demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has increased worldwide, and the aberrant DNA methylation of liver cells is a common mechanism to promote hepatic tumorigenesis. Moreover, tumor microenvironment plays a major role in neoplastic transformation. To elucidate the molecular mechanisms responsible for the cytotoxic effects of SV-LAAO in human cancer cells, this study aimed to evaluate the cytotoxicity and the alterations in DNA methylation profiler in the promoter regions of cell-cycle genes induced by BjussuLAAO-II, an LAAO from Bothrops jaracussu venom, in human hepatocellular carcinoma (HepG2) cells in monoculture and co-culture with endothelial (HUVEC) cells. Methods: BjussuLAAO-II concentrations were 0.25, 0.50, 1.00 and 5.00 μg/mL. Cell viability was assessed by MTT assay and DNA methylation of the promoter regions of 22 cell-cycle genes by EpiTect Methyl II PCR array. Results: BjussuLAAO-II decreased the cell viability of HepG2 cells in monoculture at all concentrations tested. In co-culture, 1.00 and 5.00 μg/mL induced cytotoxicity (p < 0.05). BjussuLAAO-II increased the methylation of CCND1 and decreased the methylation of CDKN1A in monoculture and GADD45A in both cell-culture models (p < 0.05). Conclusion: Data showed BjussuLAAO-II induced cytotoxicity and altered DNA methylation of the promoter regions of cell-cycle genes in HepG2 cells in monoculture and co-culture models. We suggested the analysis of DNA methylation profile of GADD45A as a potential biomarker of the cell cycle effects of BjussuLAAO-II in cancer cells. The tumor microenvironment should be considered to comprise part of biotechnological strategies during the development of snake-toxin-based novel drugs.
|
| Tipo: |
Info:eu-repo/semantics/article
|
| Idioma: |
Inglês
|
| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100305
|
| Editor: |
Centro de Estudos de Venenos e Animais Peçonhentos
|
| Relação: |
10.1590/1678-9199-jvatitd-1476-18
|
| Formato: |
text/html
|
| Fonte: |
Journal of Venomous Animals and Toxins including Tropical Diseases v.25 2019
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
