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The combination of methylsulfonylmethane and tamoxifen inhibits theJak2/STAT5b pathway and synergistically inhibits tumor growth andmetastasis in ER-positive breast cancer xenografts

Authors :
Byung Wook Cho
Wan Seop Kim
Young Beom Yoo
Young Mok Yang
Heui Soo Kim
Kyung Do Park
Don Nam Kim
Tae Sook Hwang
Jong Hwan Park
Sang Yoon Kim
Soung Hoon Chang
Youn Hee Joung
Pramod Darvin
Dong Young Kang
Hak Kyo Lee
Nipin Sp
Source :
BMC CANCER(15), BMC Cancer
Publication Year :
2015

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. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1445-0) contains supplementary material, which is available to authorized users.

Details

Language :
English
Database :
OpenAIRE
Journal :
BMC CANCER(15), BMC Cancer
Accession number :
edsair.doi.dedup.....88549d1e06be9a4cda11d8e2951209e5