Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.
Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.
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DOI：
10.1371/journal.pone.0033361
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yang YM
中科院分区：
文献类型：
--
作者：
Lim EJ;Hong DY;Park JH;Joung YH;Darvin P;Kim SY;Na YM;Hwang TS;Ye SK;Moon ES;Cho BW;Do Park K;Lee HK;Park T;Yang YM
乳腺癌是所有癌症中最具侵袭性的一种，发病率和死亡率都很高。本研究旨在探讨甲磺酰甲烷(MSM)抑制小鼠乳腺癌移植瘤生长的分子机制。MSM是一种有机含硫天然化合物，无毒。在这项研究中，我们证明了MSM以剂量依赖的方式显著降低了人乳腺癌细胞的活力。MSM还抑制受体阳性细胞株中STAT3、STAT5b的磷酸化、胰岛素样生长因子-1R、缺氧诱导因子-1α、血管内皮生长因子、蛋白酪氨酸激酶和p-胰岛素样生长因子-1R的表达，并抑制三重阴性受体的表达。此外，MSM还降低了在MDA-MB 231或共转染COS-7细胞中STAT5b和STAT3与靶基因启动子的DNA结合活性。我们证实，MSM显著降低了相对荧光素酶活性，表明STAT5b/IGF1R、STAT5b/HSP90VEGF和STAT3/α之间存在串扰。为了在体内证实这些发现，在Balb/c裸鼠体内建立了MDA-MB 231细胞的异种移植瘤，并给予MSM 30天。与我们的体外分析一致，这些异种移植瘤显示STAT3、STAT5b、IGF-1R和VEGF的表达降低。通过体外和体内的分析，我们证实MSM可以有效地调节多个靶点，包括STAT3/VEGF和STAT5b/IGF-1R。这些都是参与肿瘤发生、发展和转移的主要分子。因此，我们强烈建议使用MSM作为试验药物来治疗所有类型的乳腺癌，包括三阴性乳腺癌。
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.
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DOI：
10.1186/bcr2341
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bernaciak TM;Zareno J;Parsons JT;Silva CM
通讯作者：
Silva CM
DOI：
10.1186/bcr1748
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fowler AM;Alarid ET
通讯作者：
Alarid ET
影响因子：
6.1
作者：
Ferreira, ACS;Rodrigues, P;De Pinho, PG
通讯作者：
De Pinho, PG
影响因子：
5.2
作者：
Joung, Youn-Hee;Lim, Eun-Joung;Yang, Young Mok
通讯作者：
Yang, Young Mok
影响因子：
6.4
作者：
Dabrosin, C;Margetts, PJ;Gauldie, J
通讯作者：
Gauldie, J