Eur Rev Med Pharmacol Sci 2022; 26 (4): 1283-1292
DOI: 10.26355/eurrev_202202_28121

Experimental study on thioredoxin redox inhibitor 1-methylpropyl 2-imidazolyl disulfide promoting apoptosis of multiple myeloma cells in vitro and in vivo

Q.-D. Lin, L.-N. Liu, X.-Y. Liu, Y. Yan, B.-J. Fang, Y.-L. Zhang, J. Zhou, Y.-F. Li, W.-L. Zuo, Y.-P. Song

Henan Key Lab of Experimental Hematology, Henan Institute of Hematology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. songyongping001@126.com

 


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 AND METHODS: 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.

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Q.-D. Lin, L.-N. Liu, X.-Y. Liu, Y. Yan, B.-J. Fang, Y.-L. Zhang, J. Zhou, Y.-F. Li, W.-L. Zuo, Y.-P. Song
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
Year: 2022
Vol. 26 - N. 4
Pages: 1283-1292
DOI: 10.26355/eurrev_202202_28121