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Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive
Article

Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis

1
Department of Biomedical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
2
Department of Immunotherapeutics and Biotechnology, and Center for Tumor Immunology and Targeted Cancer Therapy, Texas Tech University Health Sciences Center, Abilene, TX 79601, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Maryam Nakhjavani and Amanda Townsend
Pharmaceuticals 2021, 14(6), 521; https://doi.org/10.3390/ph14060521
Received: 26 February 2021 / Revised: 17 May 2021 / Accepted: 22 May 2021 / Published: 28 May 2021
Triple-negative breast cancer (TNBC) is considered to be the most aggressive and malignant neoplasm and is highly metastatic in nature. In the current study, we investigated the anti-metastatic potential of atovaquone, a protozoal drug prescribed for Pneumocystis pneumonia. We showed that atovaquone induced apoptosis and reduced the survival of several aggressive metastatic TNBC cell lines including metastatic patient-derived cells by reducing the expression of integrin α6, integrin β4, FAK, Src, and Vimentin. In order to study the efficacy of atovaquone in suppressing metastasized breast tumor cells in brain and lungs, we performed three in vivo experiments. We demonstrated that oral administration of 50 mg/kg of atovaquone suppressed MDA-MB-231 breast tumor growth by 90% in lungs in an intravenous metastatic tumor model. Anti-metastatic effect of atovaquone was further determined by intracardiac injection of 4T1-luc breast tumor cells into the left ventricle of mouse heart. Our results showed that atovaquone treatment suppressed the growth of metastatic tumors in lungs, liver and brain by 70%, 50% and 30% respectively. In an intracranial model, the growth of HCC1806-luc brain tumors in atovaquone treated mice was about 55% less than that of control. Taken together, our results indicate the anti-metastatic effects of atovaquone in vitro and in vivo in various breast tumor metastasis models. View Full-Text
Keywords: atovaquone; metastasis; integrins; angiogenesis; drug repurposing; focal adhesion kinase; breast cancer; metastasis models; VEGF atovaquone; metastasis; integrins; angiogenesis; drug repurposing; focal adhesion kinase; breast cancer; metastasis models; VEGF
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MDPI and ACS Style

Gupta, N.; Srivastava, S.K. Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis. Pharmaceuticals 2021, 14, 521. https://doi.org/10.3390/ph14060521

AMA Style

Gupta N, Srivastava SK. Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis. Pharmaceuticals. 2021; 14(6):521. https://doi.org/10.3390/ph14060521

Chicago/Turabian Style

Gupta, Nehal, and Sanjay K. Srivastava. 2021. "Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis" Pharmaceuticals 14, no. 6: 521. https://doi.org/10.3390/ph14060521

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