The Evaluation of tLyP-1-Bound Mda-7/IL-24 Killing Activity on a Liver Tumor Cell Line.
Cancer Biother Radiopharm
; 36(10): 827-836, 2021 Dec.
Article
in En
| MEDLINE
| ID: mdl-32493109
ABSTRACT
Background:
The melanoma differentiation-associated gene-7 (Mda-7)/interleukin-24 (IL-24) is a tumor killing cytokine, the bystander effect of which can be enhanced through tethering to tumor homing peptides (THPs). Materials andMethods:
After fusing tLyP-1, RGR, and buforin as THPs to Mda-7/IL-24, enzyme-linked immunosorbent assay (ELISA) was used to determine the secretion potency of the recombinant proteins. The killing potency of plasmids expressing IL-24, IL-24.tLyP1, IL-24.RGR, and buf.IL-24 were assessed, using MTT, Annexin/PI staining assays, as well as measuring the expression level of GADD-153 and BCL2-associated X (BAX) on Huh-7 cells. Three-dimensional structural analysis and protein-receptor interaction were also evaluated by modeling.Results:
The ELISA result showed that contrary to IL-24.RGR and buf.IL-24, IL-24.tLyP-1 retained the secretion potency, similar to the native form. The viability assessments showed that IL-24 and IL-24.tLyP-1 had the most growth suppressive effects in comparison with the control group (p < 0.0001). Furthermore, IL-24 and IL-24.tLyP-1 had the highest apoptotic activity and significant upregulatory effect on the GADD-153 and BAX genes (p < 0.0003). The modeling showed that peptide modifications left no detrimental effect on IL-24 attachment to the cognate receptor.Conclusion:
IL-24 can tolerate tLyP-1 peptide modification by retaining its secretion potency. Tethering tLyP-1 to IL-24 can induce more apoptosis than its modified versions by RGR or buforin.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides, Cyclic
/
Transfection
/
Interleukins
/
Apoptosis
/
Liver
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cancer Biother Radiopharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2021
Document type:
Article
Affiliation country: