A peptide-salinomycin conjugate with a bystander effect reduces the stemness characteristics of ovarian cancer cells and enhances drug sensitivity.
Eur J Med Chem
; 276: 116701, 2024 Oct 05.
Article
en En
| MEDLINE
| ID: mdl-39067438
ABSTRACT
Salinomycin (Sal) has attracted considerable attention in the field of tumor treatment, especially for its inhibitory effect on cancer stem cells (CSCs) and drug-resistant tumor cells. However, its solubility and targeting specificity pose significant challenges to its pharmaceutical development. Sal-A6, a novel peptide-drug conjugate (PDC), was formed by linking the peptide A6 targeting the CSC marker CD44 with Sal using a specific linker. This conjugation markedly enhances the physicochemical properties of Sal and compared to Sal, Sal-A6 demonstrated a significantly increased activity against ovarian cancer. Furthermore, Sal-A6, employing a disulfide bond as a linker, exhibited bystander killing effect. Moreover, it induces substantial cytotoxic effect on both cancer stem cells and drug-resistant cells in addition to enhance chemosensitivity of resistant ovarian cancer cells. In summary, the results indicated that Sal-A6, a novel PDC derived from Sal, has potential therapeutic applications in the treatment of ovarian cancer and drug-resistant patients. Additionally, this discovery offers insights for developing PDC-type drugs using Sal as a foundation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Péptidos
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Piranos
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Células Madre Neoplásicas
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Ensayos de Selección de Medicamentos Antitumorales
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Antineoplásicos
Límite:
Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China