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The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts
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 av...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472404/ https://www.ncbi.nlm.nih.gov/pubmed/26084564 http://dx.doi.org/10.1186/s12885-015-1445-0 |
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author | SP, Nipin Darvin, Pramod Yoo, Young Beom Joung, Youn Hee Kang, Dong Young Kim, Don Nam Hwang, Tae Sook Kim, Sang Yoon Kim, Wan Seop Lee, Hak Kyo Cho, Byung Wook Kim, Heui Soo Park, Kyung Do Park, Jong Hwan Chang, Soung Hoon Yang, Young Mok |
author_facet | SP, Nipin Darvin, Pramod Yoo, Young Beom Joung, Youn Hee Kang, Dong Young Kim, Don Nam Hwang, Tae Sook Kim, Sang Yoon Kim, Wan Seop Lee, Hak Kyo Cho, Byung Wook Kim, Heui Soo Park, Kyung Do Park, Jong Hwan Chang, Soung Hoon Yang, Young Mok |
author_sort | SP, Nipin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4472404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44724042015-06-20 The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts SP, Nipin Darvin, Pramod Yoo, Young Beom Joung, Youn Hee Kang, Dong Young Kim, Don Nam Hwang, Tae Sook Kim, Sang Yoon Kim, Wan Seop Lee, Hak Kyo Cho, Byung Wook Kim, Heui Soo Park, Kyung Do Park, Jong Hwan Chang, Soung Hoon Yang, Young Mok BMC Cancer Research Article 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. BioMed Central 2015-06-19 /pmc/articles/PMC4472404/ /pubmed/26084564 http://dx.doi.org/10.1186/s12885-015-1445-0 Text en © SP et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article SP, Nipin Darvin, Pramod Yoo, Young Beom Joung, Youn Hee Kang, Dong Young Kim, Don Nam Hwang, Tae Sook Kim, Sang Yoon Kim, Wan Seop Lee, Hak Kyo Cho, Byung Wook Kim, Heui Soo Park, Kyung Do Park, Jong Hwan Chang, Soung Hoon Yang, Young Mok The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title | The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title_full | The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title_fullStr | The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title_full_unstemmed | The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title_short | The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts |
title_sort | combination of methylsulfonylmethane and tamoxifen inhibits the jak2/stat5b pathway and synergistically inhibits tumor growth and metastasis in er-positive breast cancer xenografts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472404/ https://www.ncbi.nlm.nih.gov/pubmed/26084564 http://dx.doi.org/10.1186/s12885-015-1445-0 |
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