title: The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts.
abstract: BACKGROUND
  Combination therapy, which reduces the dosage intensity of the individual drugs while increasing their efficacy, is not a novel approach for the treatment of cancer. Methylsulfonylmethane (MSM) is an organic sulfur compound shown to act against tumor cells. Tamoxifen is a commercially available therapeutic agent for breast malignancies.
  
  
  METHODS
  In the current study, we analyzed the combinatorial effect of MSM and tamoxifen on the suppression of ER-positive breast cancer xenograft growth and metastasis. Additionally, we also validated the molecular targets by which the drug combination regulated tumor growth and metastasis.
  
  
  RESULTS
  We observed that the combination of MSM and tamoxifen regulated cell viability and migration in vitro. The intragastric administration of MSM and subcutaneous implantation of tamoxifen tablets led to tumor growth suppression and inhibition of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5b (STAT5b) pathway. Our study also assessed the regulation of signaling molecules implicated in the growth, progression, differentiation, and migration of cancer cells, such as Jak2, STAT5b, insulin-like growth factor-1Rβ, and their phosphorylation status.
  
  
  CONCLUSIONS
  Study results indicated that this combination therapy inhibited tumor growth and metastasis. Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer.
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nipinsp@gmail.com.
authors.forename: Nipin
authors.initials: N
authors.lastname: S P
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. pramoddarvin@gmail.com.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: Department of Surgery, School of Medicine, Konkuk University, Seoul, 143-701, Korea. 0117652771@kuh.ac.kr.
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, 143-701, Korea. adada76@nate.com.
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, 143-701, Korea. kdy6459@naver.com.
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, 143-701, Korea. don1106@nate.com.
authors.forename: Don Nam
authors.initials: DN
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. tshwang@kuh.ac.kr.
authors.forename: Tae Sook
authors.initials: TS
authors.lastname: Hwang
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. sangyoon.kim@kku.ac.kr.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. wskim@kuh.ac.kr.
authors.forename: Wan Seop
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Genomic Informatics Center, Hankyong National University, Anseong, Korea. breedlee@empal.com.
authors.forename: Hak Kyo
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Animal Science, College of Life Sciences, Pusan National University, Pusan, Korea. bwcho@pusan.ac.kr.
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Korea. khs307@pusan.ac.kr.
authors.forename: Heui Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Genomic Informatics Center, Hankyong National University, Anseong, Korea. doobalo@hknu.ac.kr.
authors.forename: Kyung Do
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nihpark@yahoo.com.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Preventive Medicine, School of Medicine, Konkuk University, Chungju, 380-701, Korea. schang@kku.ac.kr.
authors.forename: Soung Hoon
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. ymyang@kku.ac.kr.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D009362:Neoplasm Metastasis; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000008:administration & dosage*; D013629:Tamoxifen / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D047628:Estrogen Receptor alpha; D017451:Receptors, Somatomedin; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D013450:Sulfones; D013629:Tamoxifen; C025910:dimethyl sulfone; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D004121:Dimethyl Sulfoxide