title: Methylsulfonylmethane inhibits HER2 expression through STAT5b in breast cancer cells.
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.
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kang
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: Department of Surgery, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Young Beom
authors.initials: YB
authors.lastname: Yoo
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Nipin
authors.initials: N
authors.lastname: Sp
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Hyo Joo
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D004121:Dimethyl Sulfoxide; D018719:Erb-b2 Receptor Tyrosine Kinases; D050799:STAT5 Transcription Factor; D013450:Sulfones; C494095:STAT5B protein, human; C025910:dimethyl sulfone; C508053:ERBB2 protein, human