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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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6806 |
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| author | Pariyakorn Udomwan Chamsai Pientong Panwad Tongchai Ati Burassakarn Nuchsupha Sunthamala Sittiruk Roytrakul Supawadee Suebsasana Tipaya Ekalaksananan |
| author_facet | Pariyakorn Udomwan Chamsai Pientong Panwad Tongchai Ati Burassakarn Nuchsupha Sunthamala Sittiruk Roytrakul Supawadee Suebsasana Tipaya Ekalaksananan |
| author_sort | Pariyakorn Udomwan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T04:56:07Z |
| format | Article |
| id | doaj.art-58b51f9231a44e67b3499d52bab362c3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:56:07Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58b51f9231a44e67b3499d52bab362c32023-12-03T13:05:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213680610.3390/ijms22136806Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell LinesPariyakorn Udomwan0Chamsai Pientong1Panwad Tongchai2Ati Burassakarn3Nuchsupha Sunthamala4Sittiruk Roytrakul5Supawadee Suebsasana6Tipaya Ekalaksananan7Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandHPV & EBV and Carcinogenesis Research (HEC) Group, Khon Kaen University, Khon Kaen 40002, ThailandFunctional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, ThailandFaculty of Pharmacy, Thammasat University (Rangsit campus), Pathum Thani 12120, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandRegardless 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.https://www.mdpi.com/1422-0067/22/13/6806human papillomaviruses (HPVs)andrographolide (Androg)tumor suppressor protein p53 (p53)proteomicscervical cancer |
| spellingShingle | Pariyakorn Udomwan Chamsai Pientong Panwad Tongchai Ati Burassakarn Nuchsupha Sunthamala Sittiruk Roytrakul Supawadee Suebsasana Tipaya Ekalaksananan Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines International Journal of Molecular Sciences human papillomaviruses (HPVs) andrographolide (Androg) tumor suppressor protein p53 (p53) proteomics cervical cancer |
| 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 | human papillomaviruses (HPVs) andrographolide (Androg) tumor suppressor protein p53 (p53) proteomics cervical cancer |
| url | https://www.mdpi.com/1422-0067/22/13/6806 |
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