Digoxin, a compound of the cardiac glycoside family, was originally prescribed for heart failure but has recently been rediscovered for its potent

 

Abstract

Digoxin, a compound of the cardiac glycoside family, was originally prescribed for heart failure but has recently been rediscovered for its potent antitumor activity. However, it has a narrow therapeutic margin due to its cardiotoxicity, limiting its safe use as an antitumor agent in clinical practice. To widen its therapeutic margin, we investigated whether the antitumor effect of digoxin is potentiated by the depletion of BCL-2-interacting cell death suppressor (BIS) in A549 lung cancer cells. BIS is a multifunctional protein that is frequently overexpressed in most human cancers including lung cancer. Our results demonstrated that the inhibitory potential of digoxin on the migratory behavior of A549 cells is significantly enhanced by BIS depletion as assessed by transwell assay and collagen-incorporated 3D spheroid culture. Western blotting revealed that combination treatment significantly reduces p-STAT3 expression. In addition, a STAT3 inhibitor substantially suppressed the aggressive phenotypes of A549 cells. Thus, our results suggest that loss of STAT3 activity is a possible molecular mechanism for the synergistic effect of digoxin and BIS depletion. Our findings suggest the sensitizing role of BIS silencing to reduce the dose of digoxin for treatment of lung cancer with a high metastatic potential.

PMID: 32029272 [PubMed - as supplied by publisher]

14:15

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

14:15

In reply to this message

pubmed: ctoall&ca or conall

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

Related Articles

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

J Am Coll Cardiol. 2020 Feb 11;75(5):467-478

Authors: Awadalla M, Mahmood SS, Groarke JD, Hassan MZO, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling LM, Jones-O'Connor M, Bakar RB, Cohen JV, Kirchberger MC, Sullivan RJ, Gupta D, Mulligan CP, Shah SP, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Lawrence DP, Mahmoudi M, Devereux RB, Forrestal BJ, Mandawat A, Lyon AR, Chen CL, Barac A, Hung J, Thavendiranathan P, Picard MH, Thuny F, Ederhy S, Fradley MG, Neilan TG