Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways
Open Access
- 2 April 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (4), e33361
- https://doi.org/10.1371/journal.pone.0033361
Abstract
Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers.Keywords
This publication has 56 references indexed in Scilit:
- Methyl Sulfone Induces Loss of Metastatic Properties and Reemergence of Normal Phenotypes in a Metastatic Cloudman S-91 (M3) Murine Melanoma Cell LinePLOS ONE, 2010
- ERα-negative and triple negative breast cancer: Molecular features and potential therapeutic approachesBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2009
- A novel role for signal transducer and activator of transcription 5b (STAT5b) in β1-integrin-mediated human breast cancer cell migrationBreast Cancer Research, 2009
- Biology, Metastatic Patterns, and Treatment of Patients with Triple-Negative Breast CancerClinical Breast Cancer, 2009
- Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6Breast Cancer Research, 2007
- Amping up estrogen receptors in breast cancerBreast Cancer Research, 2007
- The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesisOncogene, 2007
- The biology of VEGF and its receptorsNature Medicine, 2003
- Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesisOncogene, 2002
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987