Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner

© 2017, International Society for Cellular Oncology. Purpose: Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins. Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tiss...

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Main Authors: Worapong Khaodee, Nichanan Inboot, Suruk Udomsom, Warunee Kumsaiyai, Ratchada Cressey
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/46329
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spelling th-cmuir.6653943832-463292018-04-25T07:34:43Z Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner Worapong Khaodee Nichanan Inboot Suruk Udomsom Warunee Kumsaiyai Ratchada Cressey Agricultural and Biological Sciences Arts and Humanities © 2017, International Society for Cellular Oncology. Purpose: Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins. Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis. Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells. Methods: A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status. Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method. Results: We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells. We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways. Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells. Conclusions: Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes. Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer. 2018-04-25T06:52:53Z 2018-04-25T06:52:53Z 2017-12-01 Journal 22113436 22113428 2-s2.0-85029591727 10.1007/s13402-017-0349-1 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85029591727&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/46329
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Agricultural and Biological Sciences
Arts and Humanities
spellingShingle Agricultural and Biological Sciences
Arts and Humanities
Worapong Khaodee
Nichanan Inboot
Suruk Udomsom
Warunee Kumsaiyai
Ratchada Cressey
Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
description © 2017, International Society for Cellular Oncology. Purpose: Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins. Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis. Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells. Methods: A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status. Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method. Results: We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells. We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways. Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells. Conclusions: Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes. Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
format Journal
author Worapong Khaodee
Nichanan Inboot
Suruk Udomsom
Warunee Kumsaiyai
Ratchada Cressey
author_facet Worapong Khaodee
Nichanan Inboot
Suruk Udomsom
Warunee Kumsaiyai
Ratchada Cressey
author_sort Worapong Khaodee
title Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
title_short Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
title_full Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
title_fullStr Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
title_full_unstemmed Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
title_sort glucosidase ii beta subunit (gluiiβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85029591727&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/46329
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