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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/8/1632 |
| _version_ | 1797407522165882880 |
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| author | Laura C. Gunder Simon Blaine-Sauer Hillary R. Johnson Myeong-Kyun Shin Andrew S. Auyeung Wei Zhang Glen E. Leverson Ella T. Ward-Shaw Renee E. King Stephanie M. McGregor Kristina A. Matkowskyj Paul F. Lambert Evie H. Carchman |
| author_facet | Laura C. Gunder Simon Blaine-Sauer Hillary R. Johnson Myeong-Kyun Shin Andrew S. Auyeung Wei Zhang Glen E. Leverson Ella T. Ward-Shaw Renee E. King Stephanie M. McGregor Kristina A. Matkowskyj Paul F. Lambert Evie H. Carchman |
| author_sort | Laura C. Gunder |
| collection | DOAJ |
| 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: <i>K14E6/E7</i> transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with <i>Mus musculus</i> papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (<i>K14E6/E7</i>) 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 <i>K14E6/E7</i> mice. |
| first_indexed | 2024-03-09T03:42:42Z |
| format | Article |
| id | doaj.art-ac84550b4c96438b81d23af70f22f295 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:42:42Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-ac84550b4c96438b81d23af70f22f2952023-12-03T14:38:39ZengMDPI AGViruses1999-49152022-07-01148163210.3390/v14081632Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse ModelsLaura C. Gunder0Simon Blaine-Sauer1Hillary R. Johnson2Myeong-Kyun Shin3Andrew S. Auyeung4Wei Zhang5Glen E. Leverson6Ella T. Ward-Shaw7Renee E. King8Stephanie M. McGregor9Kristina A. Matkowskyj10Paul F. Lambert11Evie H. Carchman12Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USAMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USADepartment of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USAMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USADepartment of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USADepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, 3170 UW Medical Foundation Centennial Building (MFCB), 1685 Highland Avenue, Madison, WI 53705, USADepartment of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USAMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USAMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, 3170 UW Medical Foundation Centennial Building (MFCB), 1685 Highland Avenue, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, 3170 UW Medical Foundation Centennial Building (MFCB), 1685 Highland Avenue, Madison, WI 53705, USAMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USADepartment of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USAThe 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: <i>K14E6/E7</i> transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with <i>Mus musculus</i> papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (<i>K14E6/E7</i>) 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 <i>K14E6/E7</i> mice.https://www.mdpi.com/1999-4915/14/8/1632dihydroartemisininDHAartemisininpapillomavirusHPVMmuPV1 |
| spellingShingle | Laura C. Gunder Simon Blaine-Sauer Hillary R. Johnson Myeong-Kyun Shin Andrew S. Auyeung Wei Zhang Glen E. Leverson Ella T. Ward-Shaw Renee E. King Stephanie M. McGregor Kristina A. Matkowskyj Paul F. Lambert Evie H. Carchman Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models Viruses dihydroartemisinin DHA artemisinin papillomavirus HPV MmuPV1 |
| 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 | dihydroartemisinin DHA artemisinin papillomavirus HPV MmuPV1 |
| url | https://www.mdpi.com/1999-4915/14/8/1632 |
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