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Methylseleninic Acid Suppresses Breast Cancer Growth via the JAK2/STAT3 Pathway

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A Correction to this article was published on 20 October 2020

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Abstract

Previous studies show that methylseleninic acid (MSA), which is the most common selenium derivative used as a drug in humans, exerts specific cytotoxic effects in several cancer cell types. However, the complex mechanism of these effects has not been fully elucidated. Here, we demonstrate by Cell Counting Kit-8 in mouse breast cancer cell line 4T1 that MSA inhibits cell viability in a concentration-dependent (5, 10, 20 μmol/L) and time-dependent (6, 12, 24 hours) manner. Flow cytometry, Western blot, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses indicated that MSA inhibits cancer cell invasion and induces apoptosis by the activation of caspase-3, poly ADP ribose polymerase 1 (PARP1), and BCL2-associated X. Furthermore, MSA demonstrated anticancer activity by inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. The MSA treatment for 24 hours decreased the phosphorylation of JAK2 and STAT3 in 4T1 cells by Western blot. We also confirmed this with the use of a JAK2 chemical inhibitor, AG490, as a positive control. In a 4T1 orthotopic allograft model, morphological and TdT-mediated dUTP nick-end labeling analyses showed that MSA treatment (1.5 mg/kg/weight) for 28 days inhibits tumor growth consistent with the clinical anticancer drug cyclophosphamide. Our observations demonstrate that MSA is a potent anticancer drug in breast cancer and uncovered a key role of the JAK2/STAT3 pathway in modulating tumor growth.

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Change history

  • 20 October 2020

    Due to an unfortunate oversight, author names have been misspelt.

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Authors and Affiliations

  1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Changwei Qiu MD, PhD, Tao Zhang MD, PhD, Xinying Zhu MD, PhD, Jinxia Qiu MD, PhD, Kangfeng Jiang MD, PhD, Gan Zhao MD, PhD, Haichong Wu MD, PhD & Ganzhen Deng MD, PhD

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  1. Changwei Qiu MD, PhD
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  2. Tao Zhang MD, PhD
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  3. Xinying Zhu MD, PhD
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  4. Jinxia Qiu MD, PhD
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  5. Kangfeng Jiang MD, PhD
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  6. Gan Zhao MD, PhD
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  7. Haichong Wu MD, PhD
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  8. Ganzhen Deng MD, PhD
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Correspondence to Changwei Qiu MD, PhD.

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Authors’ Note

T.Z., G.Z., G.D., and C.Q. conceived and designed the experiments. T.Z., G.Z., K.J., H.W., and C.Q. performed the experiments. T.Z., K.J., H.W., and C.Q. analyzed the data. T.Z., G.Z., G.D., and C.Q. wrote the paper. All authors read and approved the final manuscript. The institutional review board of each institution approved the study protocol. All of the experimental procedures involving animals and their care conformed to the Guide for the Care and Use of Laboratory Animals of the National Veterinary Research. This study was approved by the Huazhong Agricultural University Animal Care and Use Committee. Informed consent was obtained from all individual participants included in the study.

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Qiu, C., Zhang, T., Zhu, X. et al. Methylseleninic Acid Suppresses Breast Cancer Growth via the JAK2/STAT3 Pathway. Reprod. Sci. 26, 829–838 (2019). https://doi.org/10.1177/1933719118815582

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