Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wtp53 rescue.
Antigens, Neoplasm
/ genetics
Biopsy
Carcinoma
/ drug therapy
Colon
/ drug effects
Colonic Neoplasms
/ drug therapy
Female
Humans
Inflammation
/ drug therapy
Liposomes
/ administration & dosage
Male
Middle Aged
Mitogen-Activated Protein Kinases
/ genetics
Mucous Membrane
/ drug effects
NF-kappa B
/ genetics
Pentamidine
/ administration & dosage
S100 Calcium Binding Protein beta Subunit
/ genetics
Tumor Microenvironment
/ drug effects
Tumor Suppressor Protein p53
/ genetics
S100B-wtp53
colon cancer
inflammation
pentamidine
tumour microenvironment
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
08
05
2019
revised:
06
11
2019
accepted:
29
11
2019
pubmed:
6
2
2020
medline:
29
4
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
S100B protein bridges chronic mucosal inflammation and colorectal cancer given its ability to activate NF-kappaB transcription via RAGE signalling and sequestrate pro-apoptotic wtp53. Being an S100B inhibitor, pentamidine antagonizes S100B-wtp53 interaction, restoring wtp53-mediated pro-apoptotic control in cancer cells in several types of tumours. The expression of S100B, pro-inflammatory molecules and wtp53 protein was evaluated in human biopsies deriving from controls, ulcerative colitis and colon cancer patients at baseline (a) and (b) following S100B targeting with niosomal PENtamidine VEhiculation (PENVE), to maximize drug permeabilization in the tissue. Cultured biopsies underwent immunoblot, EMSA, ELISA and biochemical assays for S100B and related pro-inflammatory/pro-apoptotic proteins. Exogenous S100B (0.005-5 μmol/L) alone, or in the presence of PENVE (0.005-5 μmol/L), was tested in control biopsies while PENVE (5 μmol/L) was evaluated on control, peritumoral, ulcerative colitis and colon cancer biopsies. Our data show that S100B level progressively increases in control, peritumoral, ulcerative colitis and colon cancer enabling a pro-inflammatory/angiogenic and antiapoptotic environment, featured by iNOS, VEGF and IL-6 up-regulation and wtp53 and Bax inhibition. PENVE inhibited S100B activity, reducing its capability to activate RAGE/phosphor-p38 MAPK/NF-kappaB and favouring its disengagement with wtp53. PENVE blocks S100B activity and rescues wtp53 expression determining pro-apoptotic control in colon cancer, suggesting pentamidine as a potential anticancer drug.
Identifiants
pubmed: 32022398
doi: 10.1111/jcmm.14943
pmc: PMC7077541
doi:
Substances chimiques
Antigens, Neoplasm
0
Liposomes
0
NF-kappa B
0
S100 Calcium Binding Protein beta Subunit
0
S100B protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Pentamidine
673LC5J4LQ
MOK protein, human
EC 2.7.11.22
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3053-3063Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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