Development of a novel apigenin prodrug ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.
Auteur(s) :
Diamantis, D. [Auteur]
Tsiailanis, A. D. [Auteur]
Papaemmanouil, C. [Auteur]
Nika, M. C. [Auteur]
Kanaki, Z. [Auteur]
Golic Grdadolnik, S. [Auteur]
Babic, A. [Auteur]
Tzakos, E. P. [Auteur]
FOURNIER, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Kushwaha, P. P. [Auteur]
Thomaidis, N. S. [Auteur]
Rampias, T. [Auteur]
Shankar, E. [Auteur]
Karakurt, S. [Auteur]
Gupta, S. [Auteur]
Tzakos, A. G. [Auteur]
Tsiailanis, A. D. [Auteur]
Papaemmanouil, C. [Auteur]
Nika, M. C. [Auteur]
Kanaki, Z. [Auteur]
Golic Grdadolnik, S. [Auteur]
Babic, A. [Auteur]
Tzakos, E. P. [Auteur]
FOURNIER, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Kushwaha, P. P. [Auteur]
Thomaidis, N. S. [Auteur]
Rampias, T. [Auteur]
Shankar, E. [Auteur]
Karakurt, S. [Auteur]
Gupta, S. [Auteur]
Tzakos, A. G. [Auteur]
Titre de la revue :
Journal of Biomolecular Structure and Dynamics
Nom court de la revue :
J Biomol Struct Dyn
Pagination :
1-22
Date de publication :
2023-08-28
ISSN :
1538-0254
Mot(s)-clé(s) en anglais :
apigenin
self-immolative
cancer
ALP inhibition
natural products
Alkaline phosphatase (ALP)
self-immolative
cancer
ALP inhibition
natural products
Alkaline phosphatase (ALP)
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a ...
Lire la suite >Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Lire moins >
Lire la suite >Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Lire moins >
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Date de dépôt :
2023-12-13T03:38:19Z
2024-01-17T14:31:28Z
2024-01-17T14:31:28Z