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Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models
The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332511/ https://www.ncbi.nlm.nih.gov/pubmed/35893697 http://dx.doi.org/10.3390/v14081632 |
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author | Gunder, Laura C. Blaine-Sauer, Simon Johnson, Hillary R. Shin, Myeong-Kyun Auyeung, Andrew S. Zhang, Wei Leverson, Glen E. Ward-Shaw, Ella T. King, Renee E. McGregor, Stephanie M. Matkowskyj, Kristina A. Lambert, Paul F. Carchman, Evie H. |
author_facet | Gunder, Laura C. Blaine-Sauer, Simon Johnson, Hillary R. Shin, Myeong-Kyun Auyeung, Andrew S. Zhang, Wei Leverson, Glen E. Ward-Shaw, Ella T. King, Renee E. McGregor, Stephanie M. Matkowskyj, Kristina A. Lambert, Paul F. Carchman, Evie H. |
author_sort | Gunder, Laura C. |
collection | PubMed |
description | The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: K14E6/E7 transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with Mus musculus papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (K14E6/E7) or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia. Mice were treated with or without topical DHA at the cervix or anus and with or without topical treatment with the chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) at the anus of in transgenic mice to induce neoplastic progression. Mice were monitored for overt tumor growth, and tissue was harvested after 20 weeks of treatment and scored for severity of histological disease. For MmuPV1-infected mice, anogenital lavages were taken to monitor for viral clearance. Tissues were also evaluated for viral gene expression at the RNA and/or protein levels. Treatment with topical DHA did not reduce dysplasia in the anogenital tract in either papillomavirus-induced mouse model and did not prevent progression to anal cancer in the DMBA-treated K14E6/E7 mice. |
format | Online Article Text |
id | pubmed-9332511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93325112022-07-29 Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models Gunder, Laura C. Blaine-Sauer, Simon Johnson, Hillary R. Shin, Myeong-Kyun Auyeung, Andrew S. Zhang, Wei Leverson, Glen E. Ward-Shaw, Ella T. King, Renee E. McGregor, Stephanie M. Matkowskyj, Kristina A. Lambert, Paul F. Carchman, Evie H. Viruses Article The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: K14E6/E7 transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with Mus musculus papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (K14E6/E7) or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia. Mice were treated with or without topical DHA at the cervix or anus and with or without topical treatment with the chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) at the anus of in transgenic mice to induce neoplastic progression. Mice were monitored for overt tumor growth, and tissue was harvested after 20 weeks of treatment and scored for severity of histological disease. For MmuPV1-infected mice, anogenital lavages were taken to monitor for viral clearance. Tissues were also evaluated for viral gene expression at the RNA and/or protein levels. Treatment with topical DHA did not reduce dysplasia in the anogenital tract in either papillomavirus-induced mouse model and did not prevent progression to anal cancer in the DMBA-treated K14E6/E7 mice. MDPI 2022-07-26 /pmc/articles/PMC9332511/ /pubmed/35893697 http://dx.doi.org/10.3390/v14081632 Text en © 2022 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 Gunder, Laura C. Blaine-Sauer, Simon Johnson, Hillary R. Shin, Myeong-Kyun Auyeung, Andrew S. Zhang, Wei Leverson, Glen E. Ward-Shaw, Ella T. King, Renee E. McGregor, Stephanie M. Matkowskyj, Kristina A. Lambert, Paul F. Carchman, Evie H. Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title | Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title_full | Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title_fullStr | Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title_full_unstemmed | Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title_short | Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models |
title_sort | efficacy of topically administered dihydroartemisinin in treating papillomavirus-induced anogenital dysplasia in preclinical mouse models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332511/ https://www.ncbi.nlm.nih.gov/pubmed/35893697 http://dx.doi.org/10.3390/v14081632 |
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