Experimental study on thioredoxin redox inhibitor 1-methylpropyl 2-imidazolyl disulfide promoting apoptosis of multiple myeloma cells in vitro and in vivo.
Eur Rev Med Pharmacol Sci
; 26(4): 1283-1292, 2022 Feb.
Article
in En
| MEDLINE
| ID: mdl-35253185
ABSTRACT
OBJECTIVE:
To explore the in vitro and in vivo experimental study of thioredoxin-1(Trx1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) promoting multiple myeloma H929 cell apoptosis, investigate the relationship between the inhibitory effect of PX-12 on H929 cells and reactive oxygen species (ROS). MATERIALS ANDMETHODS:
Inhibition of PX-12 on H929 cells in relation to reactive oxygen species (ROS), cell cycle, and apoptosis were assessed by flow cytometry. ELISA kit, IVIS Imaging, Hematoxylin and eosin (H&E) staining and immunohistochemical staining assessment were applied to assess the anti-myeloma effect in the SCID mice model established by H929EL cells.RESULTS:
PX-12 inhibited proliferation of H929 cells performed time and dose dependent style. Furthermore, it significantly induced a G2/M phase arrest of the cell cycle in H929 cells. It also increased intracellular ROS and caspase-3 activity in H929 cells indicating that cells have undergone apoptosis. There was an almost 3-5-fold decrease in tumor viability measured by the Living-Imaging system after 21 and 28 days after PX-12 injection compared with the control group. Importantly, PX-12 caused significant decrease in expression of Kappa chain in vivo assessed by immunohistochemical staining.CONCLUSIONS:
The results suggest that PX-12 may be a potential strategy for the treatment of MM, and the inhibition of TRX-1 in the treatment of myeloma deserves further research.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thioredoxins
/
Multiple Myeloma
Limits:
Animals
Language:
En
Journal:
Eur Rev Med Pharmacol Sci
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
China