Regulation of oxaliplatin and carboplatin on the assembly behavior and cytotoxicity of human islet amyloid polypeptide.
J Inorg Biochem
; 237: 111989, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-36108345
ABSTRACT
Human islet amyloid polypeptide (hIAPP) is associated with the pathology of Type II diabetes (T2DM) due to its misfolding and amyloid deposition. The peptide is widely concerned as a potential drug target, and the prevention of hIAPP fibrillation is a rational therapeutic strategy for T2DM. Platinum complexes are promising anticancer agents with good biocompatibility, they can resist the aggregation of amyloid peptides, while the effects of oxaliplatin and carboplatin on hIAPP fibrillation are unknown. In the present work, we selected the two platinum drugs to reveal their inhibition and disaggregation against hIAPP fibrillation by various biophysical methods. The two complexes impeded hIAPP fibril formation and dispersed the aggregates into small oligomers and most monomers. They also reduced peptides oligomerization and promoted rat insulinoma ß-cells viability. They bound to hIAPP mainly through metal coordination and hydrophobic interactions. Moreover, oxaliplatin showed better inhibition and regulation on peptides aggregation and cytotoxicity than carboplatin. This work is of important biomedical values for clinical platinum drugs against T2DM and other amyloidosis related diseases.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Polipéptido Amiloide de los Islotes Pancreáticos
Idioma:
En
Revista:
J Inorg Biochem
Año:
2022
Tipo del documento:
Article