Methylsulfonylmethane inhibits HER2 expression through STAT5b in breast cancer cells

Kang,Dong  Young; Darvin,Pramod; Yoo,Young  Beom; Joung,Youn  Hee; Sp,Nipin; Byun,Hyo  Joo; Yang,Young  Mok

doi:10.3892/ijo.2015.3277

Methylsulfonylmethane inhibits HER2 expression through STAT5b in breast cancer cells

Authors:
- Dong Young Kang
- Pramod Darvin
- Young Beom Yoo
- Youn Hee Joung
- Nipin Sp
- Hyo Joo Byun
- Young Mok Yang
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Affiliations: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea, Department of Surgery, School of Medicine, Konkuk University, Seoul, Republic of Korea
Published online on: December 7, 2015 https://doi.org/10.3892/ijo.2015.3277
Pages: 836-842

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Abstract

Breast cancer is the most common cancer in women globally. The factors that increase risk include: late age at ﬁrst birth, alcohol, radiation exposure, family history of breast cancer, and postmenopausal hormone therapy. Numerous drugs are being developed to treat breast cancer. Among them, Herceptin is used for the treatment of human epidermal growth factor receptor 2 (HER2)-positive cases and targets HER2 effectively and efficiently, but it is very expensive. Methylsulfonylmethane (MSM) is an organic sulfur-containing natural compound having no reported toxicity. We examined MSM in breast cancer cell lines and found it inhibited the proliferation of estrogen receptor-positive and HER2-positive breast cancer cells in a dose-dependent manner. It also suppressed the activation of STAT5b and expression of HER2 in breast cancer cells. We determined the STAT5b binding site (GAS element) in the HER2 gene. Detailed analysis showed that MSM decreased the ability of STAT5b to bind the promoter of the HER2 gene and a luciferase assay demonstrated reduced activity. We confirmed that MSM can effectively regulate STAT5b, and thereby decrease HER2 expression. Therefore, we recommend the use of MSM as an inhibitor for the management of HER2-positive breast cancers.

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