Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro
Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in mod...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-05-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/10/5/144 |
| _version_ | 1797709648067821568 |
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| author | Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez |
| author_facet | Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez |
| author_sort | Rodolfo Garza-Morales |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells. |
| first_indexed | 2024-03-12T06:40:44Z |
| format | Article |
| id | doaj.art-052680b5dcf54828ad43596d31c4206e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:40:44Z |
| publishDate | 2018-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-052680b5dcf54828ad43596d31c4206e2023-09-03T01:01:10ZengMDPI AGCancers2072-66942018-05-0110514410.3390/cancers10050144cancers10050144Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In VitroRodolfo Garza-Morales0Roxana Gonzalez-Ramos1Akiko Chiba2Roberto Montes de Oca-Luna3Lacey R. McNally4Kelly M. McMasters5Jorge G. Gomez-Gutierrez6The Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USAThe Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Surgery, School of Medicine, Wake Forest University, Winston-Salem, NC 27109, USADepartment of Histology, School of Medicine, Autonomous University of Nuevo Leon, Monterrey 64460, NL, MexicoDepartment of Cancer Biology, Wake Forest Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC 27109, USAThe Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USAThe Hiram C. Polk Jr., MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USATriple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.http://www.mdpi.com/2072-6694/10/5/144oncolyticadenovirustriple-negativebreast cancertemozolomideautophagyvirotherapy |
| spellingShingle | Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro Cancers oncolytic adenovirus triple-negative breast cancer temozolomide autophagy virotherapy |
| title | Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro |
| title_full | Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro |
| title_fullStr | Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro |
| title_full_unstemmed | Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro |
| title_short | Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro |
| title_sort | temozolomide enhances triple negative breast cancer virotherapy in vitro |
| topic | oncolytic adenovirus triple-negative breast cancer temozolomide autophagy virotherapy |
| url | http://www.mdpi.com/2072-6694/10/5/144 |
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