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 mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Garza Morales, Rodolfo, González Ramos, Roxana, Chiba, Akiko, Montes de Oca Luna, Roberto, McNally, Lacey R., McMasters, Kelly M., Gomez Gutierrez, Jorge G
Formato: Artículo
Lenguaje:inglés
Publicado: Molecular Diversity Preservation International 2018
Materias:
Acceso en línea:http://eprints.uanl.mx/16244/1/148.pdf
_version_ 1824414548288864256
author Garza Morales, Rodolfo
González Ramos, Roxana
Chiba, Akiko
Montes de Oca Luna, Roberto
McNally, Lacey R.
McMasters, Kelly M.
Gomez Gutierrez, Jorge G
author_facet Garza Morales, Rodolfo
González Ramos, Roxana
Chiba, Akiko
Montes de Oca Luna, Roberto
McNally, Lacey R.
McMasters, Kelly M.
Gomez Gutierrez, Jorge G
author_sort Garza Morales, Rodolfo
collection Repositorio Institucional
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.
format Article
id eprints-16244
institution UANL
language English
publishDate 2018
publisher Molecular Diversity Preservation International
record_format eprints
spelling eprints-162442020-06-15T12:14:39Z http://eprints.uanl.mx/16244/ Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro Garza Morales, Rodolfo González Ramos, Roxana Chiba, Akiko Montes de Oca Luna, Roberto McNally, Lacey R. McMasters, Kelly M. Gomez Gutierrez, Jorge G RC Medicina Interna, Psiquiatría, Neurología 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. Molecular Diversity Preservation International 2018-05-17 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/16244/1/148.pdf http://eprints.uanl.mx/16244/1.haspreviewThumbnailVersion/148.pdf Garza Morales, Rodolfo y González Ramos, Roxana y Chiba, Akiko y Montes de Oca Luna, Roberto y McNally, Lacey R. y McMasters, Kelly M. y Gomez Gutierrez, Jorge G (2018) Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro. Cancers, 10 (5). pp. 1-15. ISSN 2072-6694 doi:10.3390/cancers10050144
spellingShingle RC Medicina Interna, Psiquiatría, Neurología
Garza Morales, Rodolfo
González Ramos, Roxana
Chiba, Akiko
Montes de Oca Luna, Roberto
McNally, Lacey R.
McMasters, Kelly M.
Gomez Gutierrez, Jorge G
Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
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 RC Medicina Interna, Psiquiatría, Neurología
url http://eprints.uanl.mx/16244/1/148.pdf
work_keys_str_mv AT garzamoralesrodolfo temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT gonzalezramosroxana temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT chibaakiko temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT montesdeocalunaroberto temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT mcnallylaceyr temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT mcmasterskellym temozolomideenhancestriplenegativebreastcancervirotherapyinvitro
AT gomezgutierrezjorgeg temozolomideenhancestriplenegativebreastcancervirotherapyinvitro