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Selenium Anticancer Properties and Impact on Cellular Redox Status
Article

Investigating the Potential of Conjugated Selenium Redox Folic Acid as a Treatment for Triple Negative Breast Cancer

1
Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
2
University of Lorraine, 57070 Metz, France
3
Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(2), 138; https://doi.org/10.3390/antiox9020138
Received: 31 December 2019 / Revised: 24 January 2020 / Accepted: 3 February 2020 / Published: 5 February 2020
(This article belongs to the Special Issue Redox-Active Selenium Compounds in Cancer)
Previous studies have demonstrated that redox selenium compounds arrest cancer cell viability in vitro through their pro-oxidative activity by generating superoxide (O2•−). Currently, there are no efficacious treatment options for women with Triple Negative Breast Cancer (TNBC). However, the association between the over-expression of the Folate Receptor Alpha (FRA) in TNBC and other cancer cells, has led to the possibility that TNBCs might be treated by targeting the FRA with redox selenium covalent Folic Acid conjugates. The present study reports the synthesis of the redox active vitamer, Selenofolate, generating superoxide. Superoxide (O2•−) catalytic generation by Selenofolate was assessed by an in vitro chemiluminescence (CL) assay and by a Dihydroethidium (DHE) in vivo assay. Cytotoxicity of Selenofolate was assessed against the TNBC cell line MDA-MB-468 and an immortalized, mammary epithelial cell line, HME50-5E. Cytotoxicity of Selenofolate was compared to Folic Acid and sodium selenite, in a time and dose dependent manner. Selenofolate and selenite treatments resulted in greater inhibition of MDA-MB-468 cell proliferation than HME50-5E as evaluated by Trypan Blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolic assay and Annexin V apoptosis assays. Folate receptor alpha (FRA) protein expression was assessed by Western blotting, with the experimental results showing that redox active Selenofolate and selenite, but not Folic Acid, was cytotoxic to MDA-MB-468 cells in vitro, suggesting a possible clinical option for treating TNBC and other cancers over-expressing FRA. View Full-Text
Keywords: Selenofolate; Folic Acid; selenium; superoxide; TNBC cells; MDA-MB-468 cells; mammary epithelial cells; HME50-5E cells; targeted cancer therapy Selenofolate; Folic Acid; selenium; superoxide; TNBC cells; MDA-MB-468 cells; mammary epithelial cells; HME50-5E cells; targeted cancer therapy
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MDPI and ACS Style

Khandelwal, S.; Boylan, M.; Kirsch, G.; Spallholz, J.E.; Gollahon, L.S. Investigating the Potential of Conjugated Selenium Redox Folic Acid as a Treatment for Triple Negative Breast Cancer. Antioxidants 2020, 9, 138. https://doi.org/10.3390/antiox9020138

AMA Style

Khandelwal S, Boylan M, Kirsch G, Spallholz JE, Gollahon LS. Investigating the Potential of Conjugated Selenium Redox Folic Acid as a Treatment for Triple Negative Breast Cancer. Antioxidants. 2020; 9(2):138. https://doi.org/10.3390/antiox9020138

Chicago/Turabian Style

Khandelwal, Soni, Mallory Boylan, Gilbert Kirsch, Julian E. Spallholz, and Lauren S. Gollahon 2020. "Investigating the Potential of Conjugated Selenium Redox Folic Acid as a Treatment for Triple Negative Breast Cancer" Antioxidants 9, no. 2: 138. https://doi.org/10.3390/antiox9020138

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