A potential role of calpains in sulfonylureas (SUs) -mediated death of human pancreatic cancer cells (1.2B4).
Toxicol In Vitro
; 73: 105128, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33652124
ABSTRACT
Sulfonylureas (SUs) are suggested to accelerate the pancreatic ß-cells mass loss via apoptosis. However, little is known whether calpains mediate this process. The aim of the present study is to evaluate the involvement of calpains in SUs-induced death of human pancreatic cancer (PC) cell line 1.2B4. The cells were exposed to glibenclamide, glimepiride and gliclazide for 72 h. The expression analysis of caspase-3 (CASP-3), TP53, calpain 1 (CAPN-1), calpain 2 (CAPN-2) and calpain 10 (CAPN-10) was detected using RT-PCR method. Intracellular Ca2+ concentrations, CASP-3 activity and total calpain activity were also evaluated. Our results have shown that glibenclamide and glimepiride decrease 1.2B4 cells viability with accompanied increase in intracellular Ca2+ concentration and increased expression of apoptosis-related CASP-3 and TP53. Gliclazide did not affect 1.2B4 cell viability and Ca2+ concentration, however, it downregulated CASP-3 and upregulated TP53. Interestingly, 50 µM glimepiride increased expression of CAPN-1, CAPN-2 and CAPN-10 whereas 50 µM glibenclamide solely upregulated CAPN-2 expression. We have shown that 10 µM and 50 µM glibenclamide and glimepiride increased the activity of CASP-3, but decreased total calpain activity. Our results suggest that calpains may be involved in glibenclamide- and glimepiride-induced death of PC cells. However, further investigation is required to confirm the engagement of calpains in SUs-mediated death of PC cells, especially studies on protein level of particular isoforms of calpains should be conducted.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Compostos de Sulfonilureia
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Calpaína
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Hipoglicemiantes
Limite:
Humans
Idioma:
En
Revista:
Toxicol In Vitro
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article