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

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

Author information

1
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nipinsp@gmail.com.
2
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. pramoddarvin@gmail.com.
3
Department of Surgery, School of Medicine, Konkuk University, Seoul, 143-701, Korea. 0117652771@kuh.ac.kr.
4
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. adada76@nate.com.
5
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. kdy6459@naver.com.
6
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. don1106@nate.com.
7
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. tshwang@kuh.ac.kr.
8
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. sangyoon.kim@kku.ac.kr.
9
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. wskim@kuh.ac.kr.
10
Genomic Informatics Center, Hankyong National University, Anseong, Korea. breedlee@empal.com.
11
Department of Animal Science, College of Life Sciences, Pusan National University, Pusan, Korea. bwcho@pusan.ac.kr.
12
Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Korea. khs307@pusan.ac.kr.
13
Genomic Informatics Center, Hankyong National University, Anseong, Korea. doobalo@hknu.ac.kr.
14
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nihpark@yahoo.com.
15
Department of Preventive Medicine, School of Medicine, Konkuk University, Chungju, 380-701, Korea. schang@kku.ac.kr.
16
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. ymyang@kku.ac.kr.

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.

PMID:
26084564
PMCID:
PMC4472404
DOI:
10.1186/s12885-015-1445-0
[Indexed for MEDLINE]
Free PMC Article

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