Development of a novel apigenin prodrug ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.
Author(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]
![refId](/themes/Mirage2//images/idref.png)
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
![refId](/themes/Mirage2//images/idref.png)
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]
Journal title :
Journal of Biomolecular Structure and Dynamics
Abbreviated title :
J Biomol Struct Dyn
Pages :
1-22
Publication date :
2023-08-28
ISSN :
1538-0254
English keyword(s) :
apigenin
self-immolative
cancer
ALP inhibition
natural products
Alkaline phosphatase (ALP)
self-immolative
cancer
ALP inhibition
natural products
Alkaline phosphatase (ALP)
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [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 ...
Show more >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.Show less >
Show more >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.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2023-12-13T03:38:19Z
2024-01-17T14:31:28Z
2024-01-17T14:31:28Z