Anti-Colorectal Cancer Effects of Probiotic-Derived p8 Protein.
Antineoplastic Agents
/ pharmacology
Bacterial Proteins
/ pharmacology
CDC2 Protein Kinase
/ metabolism
Cell Line, Tumor
Cell Proliferation
/ drug effects
Colorectal Neoplasms
/ metabolism
Cyclin B1
/ metabolism
Cyclin-Dependent Kinase Inhibitor p21
/ metabolism
Endocytosis
G2 Phase
Humans
Lacticaseibacillus rhamnosus
/ chemistry
Probiotics
/ chemistry
Signal Transduction
Tumor Suppressor Protein p53
/ metabolism
Lactobacillus rhamnosus KCTC 12202BP
anti-cancer activity
drug delivery system
gene therapy
p8
probiotics
therapeutic protein
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
19 08 2019
19 08 2019
Historique:
received:
01
07
2019
revised:
10
08
2019
accepted:
13
08
2019
entrez:
22
8
2019
pubmed:
23
8
2019
medline:
10
1
2020
Statut:
epublish
Résumé
Recently, we reported a novel therapeutic probiotic-derived protein, p8, which has anti-colorectal cancer (anti-CRC) properties. In vitro experiments using a CRC cell line (DLD-1), anti-proliferation activity (about 20%) did not improve after increasing the dose of recombinant-p8 (r-p8) to >10 μM. Here, we show that this was due to the low penetrative efficiency of r-p8 exogenous treatment. Furthermore, we found that r-p8 entered the cytosol through endocytosis, which might be a reason for the low penetration efficiency. Therefore, to improve the therapeutic efficacy of p8, we tried to improve delivery to CRC cells. This resulted in endogenous expression of p8 and increased the anti-proliferative effects by up to 2-fold compared with the exogenous treatment (40 μM). Anti-migration activity also increased markedly. Furthermore, we found that the anti-proliferation activity of p8 was mediated by inhibition of the p53-p21-Cyclin B1/Cdk1 signal pathway, resulting in growth arrest at the G
Identifiants
pubmed: 31430963
pii: genes10080624
doi: 10.3390/genes10080624
pmc: PMC6723380
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bacterial Proteins
0
Cyclin B1
0
Cyclin-Dependent Kinase Inhibitor p21
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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