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Temozolomide enhances triple-negative breast cancer virotherapy in vitro

Publication ,  Journal Article
Garza-Morales, R; Gonzalez-Ramos, R; Chiba, A; De Oca-Luna, RM; McNally, LR; McMasters, KM; Gomez-Gutierrez, JG
Published in: Cancers
May 1, 2018

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.

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Published In

Cancers

DOI

EISSN

2072-6694

Publication Date

May 1, 2018

Volume

10

Issue

5

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

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MLA
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Garza-Morales, R., Gonzalez-Ramos, R., Chiba, A., De Oca-Luna, R. M., McNally, L. R., McMasters, K. M., & Gomez-Gutierrez, J. G. (2018). Temozolomide enhances triple-negative breast cancer virotherapy in vitro. Cancers, 10(5). https://doi.org/10.3390/cancers10050144
Garza-Morales, R., R. Gonzalez-Ramos, A. Chiba, R. M. De Oca-Luna, L. R. McNally, K. M. McMasters, and J. G. Gomez-Gutierrez. “Temozolomide enhances triple-negative breast cancer virotherapy in vitro.” Cancers 10, no. 5 (May 1, 2018). https://doi.org/10.3390/cancers10050144.
Garza-Morales R, Gonzalez-Ramos R, Chiba A, De Oca-Luna RM, McNally LR, McMasters KM, et al. Temozolomide enhances triple-negative breast cancer virotherapy in vitro. Cancers. 2018 May 1;10(5).
Garza-Morales, R., et al. “Temozolomide enhances triple-negative breast cancer virotherapy in vitro.” Cancers, vol. 10, no. 5, May 2018. Scopus, doi:10.3390/cancers10050144.
Garza-Morales R, Gonzalez-Ramos R, Chiba A, De Oca-Luna RM, McNally LR, McMasters KM, Gomez-Gutierrez JG. Temozolomide enhances triple-negative breast cancer virotherapy in vitro. Cancers. 2018 May 1;10(5).

Published In

Cancers

DOI

EISSN

2072-6694

Publication Date

May 1, 2018

Volume

10

Issue

5

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis