Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers.
María Sánchez-MillaLaura Muñoz-MorenoJavier Sánchez NievesMarek MalýRafael Gómez-RamírezMaría J CarmenaFrancisco Javier de La MataPublished in: Biomacromolecules (2019)
The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration. Also, the dendriplexes were not toxic for no tumoral prostate cells (RPWE-1) or fibroblasts. The use of labeled GHRH peptide (rhodamine labeled) and a dendrimer (fluorescein labeled) allowed us to observe that both systems reach the intracellular milieu after dendriplex formation. The treatment of PC3 cells with the nanoplexes reduced expression of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP). Molecular modeling analysis highlights the important contribution of the carbosilane framework in the stabilization of the dendriplex, since dendrimer interacts with a peptide region where hydrophobic amino acids are presented.
Keyphrases
- prostate cancer
- vascular endothelial growth factor
- cell migration
- amino acid
- radical prostatectomy
- growth hormone
- cell adhesion
- pet imaging
- endothelial cells
- binding protein
- induced apoptosis
- poor prognosis
- small cell lung cancer
- squamous cell carcinoma
- cell cycle arrest
- oxidative stress
- long non coding rna
- combination therapy
- cell proliferation
- extracellular matrix
- cell death