Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer
LINE1 retrotransposons, which are thought to be the remnants of ancient integrations of retrovirus-like elements, are aberrantly (re)activated in many cancer cells. Due to LINE1-induced alterations in target gene expression and/or chromosomal rearrangements, they may be important drivers of tumorige...
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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/12/2396 |
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| author | Marcel A. Schneider Anton A. Buzdin Achim Weber Pierre-Alain Clavien Pieter Borger |
| author_facet | Marcel A. Schneider Anton A. Buzdin Achim Weber Pierre-Alain Clavien Pieter Borger |
| author_sort | Marcel A. Schneider |
| collection | DOAJ |
| description | LINE1 retrotransposons, which are thought to be the remnants of ancient integrations of retrovirus-like elements, are aberrantly (re)activated in many cancer cells. Due to LINE1-induced alterations in target gene expression and/or chromosomal rearrangements, they may be important drivers of tumorigenesis. Moreover, LINE1 encoded proteins, Open Reading Frame (ORF)1 and ORF2, may have pro-oncogenic potential through inductors of oncogenic transcription factors or inhibitors of cell cycle suppressors. The current study therefore aimed to investigate in vitro and in vivo anti-tumorigenic effects of two well-known antiretroviral drugs, zidovudine, a nucleoside analogue inhibitor of RT (NRTI), and efavirenz, a non-nucleoside RT inhibitor (NNRTI). Our data demonstrate that both drugs in clinically relevant doses significantly reduced the proliferation of murine and human cancer cell lines, as well as growth of tumors in a murine subcutaneous model. Intriguingly, we found that the combination of both zidovudine and efavirenz almost entirely blocked tumorigenesis in vivo. Because both drugs are FDA-approved agents and the combination was very well tolerated in mice, the combination therapy as presented in our paper might be an opportunity to treat colorectal tumors and metastasis to the liver in an inexpensive way. |
| first_indexed | 2024-03-10T03:55:00Z |
| format | Article |
| id | doaj.art-436624fe208b4cc78d6684f453c6bc80 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T03:55:00Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-436624fe208b4cc78d6684f453c6bc802023-11-23T10:57:20ZengMDPI AGViruses1999-49152021-11-011312239610.3390/v13122396Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of CancerMarcel A. Schneider0Anton A. Buzdin1Achim Weber2Pierre-Alain Clavien3Pieter Borger4Laboratory of the Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, SwitzerlandMoscow Institute of Physics and Technology, Dolgoprudny, 141701 Moscow, RussiaInstitute for Pathology, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, SwitzerlandLaboratory of the Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, SwitzerlandLaboratory of the Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, SwitzerlandLINE1 retrotransposons, which are thought to be the remnants of ancient integrations of retrovirus-like elements, are aberrantly (re)activated in many cancer cells. Due to LINE1-induced alterations in target gene expression and/or chromosomal rearrangements, they may be important drivers of tumorigenesis. Moreover, LINE1 encoded proteins, Open Reading Frame (ORF)1 and ORF2, may have pro-oncogenic potential through inductors of oncogenic transcription factors or inhibitors of cell cycle suppressors. The current study therefore aimed to investigate in vitro and in vivo anti-tumorigenic effects of two well-known antiretroviral drugs, zidovudine, a nucleoside analogue inhibitor of RT (NRTI), and efavirenz, a non-nucleoside RT inhibitor (NNRTI). Our data demonstrate that both drugs in clinically relevant doses significantly reduced the proliferation of murine and human cancer cell lines, as well as growth of tumors in a murine subcutaneous model. Intriguingly, we found that the combination of both zidovudine and efavirenz almost entirely blocked tumorigenesis in vivo. Because both drugs are FDA-approved agents and the combination was very well tolerated in mice, the combination therapy as presented in our paper might be an opportunity to treat colorectal tumors and metastasis to the liver in an inexpensive way.https://www.mdpi.com/1999-4915/13/12/2396combination therapyantiretroviral drugszidovudineefavirenzcancer treatment |
| spellingShingle | Marcel A. Schneider Anton A. Buzdin Achim Weber Pierre-Alain Clavien Pieter Borger Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer Viruses combination therapy antiretroviral drugs zidovudine efavirenz cancer treatment |
| title | Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer |
| title_full | Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer |
| title_fullStr | Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer |
| title_full_unstemmed | Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer |
| title_short | Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer |
| title_sort | combination of antiretroviral drugs zidovudine and efavirenz impairs tumor growths in a mouse model of cancer |
| topic | combination therapy antiretroviral drugs zidovudine efavirenz cancer treatment |
| url | https://www.mdpi.com/1999-4915/13/12/2396 |
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