Effects of Atypical Protein Kinase C Inhibitor (DNDA) on Lung Cancer Proliferation and Migration by PKC-ι/FAK Ubiquitination Through the Cbl-b Pathway

OncoTargets and Therapy
Raja Reddy BommaReddyMildred Acevedo-Duncan

Abstract

The options for treating lung cancers are limited, as diagnosis typically occurs during the late stages of the disease. There is a dire need to develop aPKC (atypical Protein Kinase C) inhibitors due to aPKC overexpression and contributions to lung cancer malignancies. In this study, we investigate the role of atypical PKCs (aPKCs) in cell proliferation and migration in lung cancer cell lines and the effect of the novel aPKC inhibitor DNDA (3,4-amino-2,7 napthalene disulfonic acid). The normal and lung cancer cells were treated with various concentrations of DNDA. We used a WST assay to determine lung cell viability, then analyzed cell apoptosis through Annexin V/PI staining and flow cytometry. Immunoprecipitation determined the proteins' associations, and Western blot allowed testing of the expression of interest proteins. We also employed the UbiTest to identify the ubiquitination of the FAK. The scratch and transwell assays measured cell migration and invasion of lung cancer cells. Our data from cell viability and flow cytometry showed a significant reduction in cell proliferation and induction of apoptosis with DNDA treatment in lung cancer cells, as well as no toxic effect on normal BEAS-2B lung cells. Western blot results...Continue Reading

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Citations

Dec 12, 2020·Clinical and Experimental Immunology·D JafariA Esmaeilzadeh
Jun 3, 2021·International Journal of Molecular Sciences·Mohammad Mojtaba SadeghiYusuf A Hannun
Oct 11, 2021·Cancer Cell International·Yingyue LouDuo Zhang

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Methods Mentioned

BETA
ubiquitination
Assay
protein assay
electrophoresis
Fluorescence
transfection
pulldown
flow cytometry
transfect
Immunoprecipitation

Software Mentioned

UbiTest
ProgRes Capture
R Studio
FacsDiva6
Alpha View Simple
ImageJ

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