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Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines

Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked...

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Autores principales: Udomwan, Pariyakorn, Pientong, Chamsai, Tongchai, Panwad, Burassakarn, Ati, Sunthamala, Nuchsupha, Roytrakul, Sittiruk, Suebsasana, Supawadee, Ekalaksananan, Tipaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268713/
https://www.ncbi.nlm.nih.gov/pubmed/34202736
http://dx.doi.org/10.3390/ijms22136806
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author Udomwan, Pariyakorn
Pientong, Chamsai
Tongchai, Panwad
Burassakarn, Ati
Sunthamala, Nuchsupha
Roytrakul, Sittiruk
Suebsasana, Supawadee
Ekalaksananan, Tipaya
author_facet Udomwan, Pariyakorn
Pientong, Chamsai
Tongchai, Panwad
Burassakarn, Ati
Sunthamala, Nuchsupha
Roytrakul, Sittiruk
Suebsasana, Supawadee
Ekalaksananan, Tipaya
author_sort Udomwan, Pariyakorn
collection PubMed
description Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions.
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spelling pubmed-82687132021-07-10 Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines Udomwan, Pariyakorn Pientong, Chamsai Tongchai, Panwad Burassakarn, Ati Sunthamala, Nuchsupha Roytrakul, Sittiruk Suebsasana, Supawadee Ekalaksananan, Tipaya Int J Mol Sci Article Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions. MDPI 2021-06-24 /pmc/articles/PMC8268713/ /pubmed/34202736 http://dx.doi.org/10.3390/ijms22136806 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Udomwan, Pariyakorn
Pientong, Chamsai
Tongchai, Panwad
Burassakarn, Ati
Sunthamala, Nuchsupha
Roytrakul, Sittiruk
Suebsasana, Supawadee
Ekalaksananan, Tipaya
Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title_full Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title_fullStr Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title_full_unstemmed Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title_short Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
title_sort proteomics analysis of andrographolide-induced apoptosis via the regulation of tumor suppressor p53 proteolysis in cervical cancer-derived human papillomavirus 16-positive cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268713/
https://www.ncbi.nlm.nih.gov/pubmed/34202736
http://dx.doi.org/10.3390/ijms22136806
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