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TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells

Esophageal squamous cell carcinoma accounts for a large proportion of cancer-associated mortalities in both men and women. Melittin is the major active component of bee venom, which has been reported to possess anti-inflammatory, antibacterial and anti-cancer properties. The aim of the present study...

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Autores principales: Zhou, Chao, Ma, Jie, Lu, Yuanhua, Zhao, Wan, Xu, Bingxue, Lin, Jian, Ma, Yongjun, Tian, Yafei, Zhang, Qi, Wang, Wei, Yan, Weiqun, Jiao, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681202/
https://www.ncbi.nlm.nih.gov/pubmed/33240422
http://dx.doi.org/10.3892/ol.2020.12277
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author Zhou, Chao
Ma, Jie
Lu, Yuanhua
Zhao, Wan
Xu, Bingxue
Lin, Jian
Ma, Yongjun
Tian, Yafei
Zhang, Qi
Wang, Wei
Yan, Weiqun
Jiao, Ping
author_facet Zhou, Chao
Ma, Jie
Lu, Yuanhua
Zhao, Wan
Xu, Bingxue
Lin, Jian
Ma, Yongjun
Tian, Yafei
Zhang, Qi
Wang, Wei
Yan, Weiqun
Jiao, Ping
author_sort Zhou, Chao
collection PubMed
description Esophageal squamous cell carcinoma accounts for a large proportion of cancer-associated mortalities in both men and women. Melittin is the major active component of bee venom, which has been reported to possess anti-inflammatory, antibacterial and anti-cancer properties. The aim of the present study was to construct a tumor targeted recombinant plasmid [pc-telomerase reverse transcriptase (TERT)-melittin] containing a human TERT promoter followed by a melittin coding sequence and to explore the effects of this plasmid in esophageal cell carcinoma and investigate preliminarily the underlying mechanisms of this effect. TE1 cells were transfected with pcTERT-melittin and the resulting apoptosis was subsequently examined. The viability of TE1 cells transfected with pcTERT-melittin was measured using a Cell Counting Kit-8 assay, which indicated inhibited proliferation. The disruption of mitochondrial membranes and the concomitant production of reactive oxygen species demonstrated an inducible apoptotic effect of melittin in TE1 cells. Apoptotic cells were also counted using an Annexin V-FITC and PI double-staining assay. The upregulation of cleaved caspase-9, cleaved caspase-3, Bax and poly(ADP-ribose) polymerase 1 in pcTERT-melittin transfected TE1 cells, suggested that pcTERT-melittin-induced apoptosis was associated with the mitochondrial pathway. TE1 cells were also arrested in the G(0)/G(1) phase when transfected with pcTERT-melittin, followed by the decline of CDK4, CDK6 and cyclin D1 expression levels. As cell invasion and metastasis are common in patients with esophageal cancer, a cell migration assay was conducted and it was found that pcTERT-melittin transfection reduced the migratory and invasive abilities of TE1 cells. The findings of the present study demonstrated that pcTERT-melittin may induce apoptosis of esophageal carcinoma cells and inhibit tumor metastasis.
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spelling pubmed-76812022020-11-24 TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells Zhou, Chao Ma, Jie Lu, Yuanhua Zhao, Wan Xu, Bingxue Lin, Jian Ma, Yongjun Tian, Yafei Zhang, Qi Wang, Wei Yan, Weiqun Jiao, Ping Oncol Lett Articles Esophageal squamous cell carcinoma accounts for a large proportion of cancer-associated mortalities in both men and women. Melittin is the major active component of bee venom, which has been reported to possess anti-inflammatory, antibacterial and anti-cancer properties. The aim of the present study was to construct a tumor targeted recombinant plasmid [pc-telomerase reverse transcriptase (TERT)-melittin] containing a human TERT promoter followed by a melittin coding sequence and to explore the effects of this plasmid in esophageal cell carcinoma and investigate preliminarily the underlying mechanisms of this effect. TE1 cells were transfected with pcTERT-melittin and the resulting apoptosis was subsequently examined. The viability of TE1 cells transfected with pcTERT-melittin was measured using a Cell Counting Kit-8 assay, which indicated inhibited proliferation. The disruption of mitochondrial membranes and the concomitant production of reactive oxygen species demonstrated an inducible apoptotic effect of melittin in TE1 cells. Apoptotic cells were also counted using an Annexin V-FITC and PI double-staining assay. The upregulation of cleaved caspase-9, cleaved caspase-3, Bax and poly(ADP-ribose) polymerase 1 in pcTERT-melittin transfected TE1 cells, suggested that pcTERT-melittin-induced apoptosis was associated with the mitochondrial pathway. TE1 cells were also arrested in the G(0)/G(1) phase when transfected with pcTERT-melittin, followed by the decline of CDK4, CDK6 and cyclin D1 expression levels. As cell invasion and metastasis are common in patients with esophageal cancer, a cell migration assay was conducted and it was found that pcTERT-melittin transfection reduced the migratory and invasive abilities of TE1 cells. The findings of the present study demonstrated that pcTERT-melittin may induce apoptosis of esophageal carcinoma cells and inhibit tumor metastasis. D.A. Spandidos 2021-01 2020-11-06 /pmc/articles/PMC7681202/ /pubmed/33240422 http://dx.doi.org/10.3892/ol.2020.12277 Text en Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhou, Chao
Ma, Jie
Lu, Yuanhua
Zhao, Wan
Xu, Bingxue
Lin, Jian
Ma, Yongjun
Tian, Yafei
Zhang, Qi
Wang, Wei
Yan, Weiqun
Jiao, Ping
TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title_full TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title_fullStr TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title_full_unstemmed TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title_short TERT promoter regulating melittin expression induces apoptosis and G(0)/G(1) cell cycle arrest in esophageal carcinoma cells
title_sort tert promoter regulating melittin expression induces apoptosis and g(0)/g(1) cell cycle arrest in esophageal carcinoma cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681202/
https://www.ncbi.nlm.nih.gov/pubmed/33240422
http://dx.doi.org/10.3892/ol.2020.12277
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