The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts

BMC Cancer. 2015 Jun 19;15:474. doi: 10.1186/s12885-015-1445-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dimethyl Sulfoxide / administration & dosage*
  • Estrogen Receptor alpha / genetics
  • Female
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics*
  • Neoplasm Metastasis
  • Receptors, Somatomedin / antagonists & inhibitors
  • Receptors, Somatomedin / genetics
  • STAT5 Transcription Factor / antagonists & inhibitors
  • STAT5 Transcription Factor / genetics*
  • Signal Transduction / drug effects
  • Sulfones / administration & dosage*
  • Tamoxifen / administration & dosage*
  • Xenograft Model Antitumor Assays


  • Estrogen Receptor alpha
  • Receptors, Somatomedin
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • Sulfones
  • Tamoxifen
  • dimethyl sulfone
  • JAK2 protein, human
  • Janus Kinase 2
  • Dimethyl Sulfoxide