Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways

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.

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

“…In addition, the apoptosis rate was increased 6-fold in all of liver cancer cell lines treated with 500 mmol/L compared to control. These results indicate that MSM is efficacious with treatment of the highest dose in liver cancer cells, consistent with the result that MSM suppresses breast cancer cell growth at 300 mmol/L [10] . MSM is an edible natural organic compound present in many food items and is not associated with any toxic effects, even at higher concentrations [16,17] .…”

“…The chemical structure of MSM is a combination of oxygen in dimethyl sulfoxide (DMSO), so also called dimethyl sulfone (DMSO2). The anti-inflammatory effects of MSM on lipopolysaccharide-induced inflammatory responses in murine macrophages [9] and effects of MSM in breast cancer by down regulating STAT3 and STAT5b pathways [10] were reported. However, the effect of MSM has not been studied in liver cancer.…”

“…Moreover, the effect of MSM has been reported in cancer. MSM suppresses breast cancer growth by down-regulating signal transducer and activator of transcription 3 (STAT3) and signal transducer and activator of transcription 5b (STAT5b) pathways [10] . Apoptotic effects in other cancer cells, such as esophageal, gastric and liver cancer cells, were reported [11] .…”

Methylsulfonylmethane Induces G1 Arrest and Mitochondrial Apoptosis in YD-38 Gingival Cancer Cells

“…It is mainly present in foods like fruits, vegetables, and beverages. MSM can be taken up through the diet (11,12). MSM is used as a drug to alleviate pain and improve physical function in osteoarthritis (13).…”

miR-221/222 control luminal breast cancer tumor progression by regulating different targets

“…However, observations that STAT5 inhibition in breast cancers impairs the proliferative rate suggest that the role of STAT5 in breast cancer is still open to debate. 31,32 Self-governing molecular mechanisms in breast cancer development and progression have been widely explored. Likewise, the role of β4 integrin as a signaling receptor in mammary tumors has been extensively documented.…”