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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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 |
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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 |
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© 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. |
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Worapong Khaodee Nichanan Inboot Suruk Udomsom Warunee Kumsaiyai Ratchada Cressey |
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Worapong Khaodee Nichanan Inboot Suruk Udomsom Warunee Kumsaiyai Ratchada Cressey |
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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 |
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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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