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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.

S P N, Darvin P, Yoo YB, Joung YH, Kang DY, Kim DN, Hwang TS, Kim SY, Kim WS, Lee HK, Cho BW, Kim HS, Park KD, Park JH, Chang SH, Yang YM - BMC Cancer (2015)

Bottom Line: 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.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.Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nipinsp@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

The MSM-Tam combination synergistically inhibited the downstream targets of the STAT5b pathway. (a) Western blotting analysis showing total protein levels of the downstream targets of STAT5b following treatment with the drug combination in MCF-7 and T47D cells. (b) Graphical analysis of the action of the drug combination and the individual agents on the downstream targets of STAT5b in cytoplasmic proteins. (c) RT-PCR analysis of RNA levels of downstream targets of STAT5b after the treatment with Tam, MSM, and the drug combination for 24 h in MCF-7 and T47D cells. (d) Inhibition of RNA levels by the drug combination, Tam, and MSM relative to the percentage of 18 s RNA
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Fig3: The MSM-Tam combination synergistically inhibited the downstream targets of the STAT5b pathway. (a) Western blotting analysis showing total protein levels of the downstream targets of STAT5b following treatment with the drug combination in MCF-7 and T47D cells. (b) Graphical analysis of the action of the drug combination and the individual agents on the downstream targets of STAT5b in cytoplasmic proteins. (c) RT-PCR analysis of RNA levels of downstream targets of STAT5b after the treatment with Tam, MSM, and the drug combination for 24 h in MCF-7 and T47D cells. (d) Inhibition of RNA levels by the drug combination, Tam, and MSM relative to the percentage of 18 s RNA

Mentions: In the previous section, we found that the MSM-Tam combination synergistically inhibited the STAT5b-DNA binding properties. This inhibition of the DNA binding activities of STAT5b should result in impaired transcription promoter functions. In order to confirm this, the expression of STAT5b downstream targets was analyzed at both the transcriptional (Fig. 3c and d) and translational (Fig. 3a and b) levels. In both cell lines, the expression of cyclin D1, VEGF, IGF-1, and IGF-1Rβ were found to decline in the combination-treated samples (Fig. 3).Fig. 3


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

S P N, Darvin P, Yoo YB, Joung YH, Kang DY, Kim DN, Hwang TS, Kim SY, Kim WS, Lee HK, Cho BW, Kim HS, Park KD, Park JH, Chang SH, Yang YM - BMC Cancer (2015)

The MSM-Tam combination synergistically inhibited the downstream targets of the STAT5b pathway. (a) Western blotting analysis showing total protein levels of the downstream targets of STAT5b following treatment with the drug combination in MCF-7 and T47D cells. (b) Graphical analysis of the action of the drug combination and the individual agents on the downstream targets of STAT5b in cytoplasmic proteins. (c) RT-PCR analysis of RNA levels of downstream targets of STAT5b after the treatment with Tam, MSM, and the drug combination for 24 h in MCF-7 and T47D cells. (d) Inhibition of RNA levels by the drug combination, Tam, and MSM relative to the percentage of 18 s RNA
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472404&req=5

Fig3: The MSM-Tam combination synergistically inhibited the downstream targets of the STAT5b pathway. (a) Western blotting analysis showing total protein levels of the downstream targets of STAT5b following treatment with the drug combination in MCF-7 and T47D cells. (b) Graphical analysis of the action of the drug combination and the individual agents on the downstream targets of STAT5b in cytoplasmic proteins. (c) RT-PCR analysis of RNA levels of downstream targets of STAT5b after the treatment with Tam, MSM, and the drug combination for 24 h in MCF-7 and T47D cells. (d) Inhibition of RNA levels by the drug combination, Tam, and MSM relative to the percentage of 18 s RNA
Mentions: In the previous section, we found that the MSM-Tam combination synergistically inhibited the STAT5b-DNA binding properties. This inhibition of the DNA binding activities of STAT5b should result in impaired transcription promoter functions. In order to confirm this, the expression of STAT5b downstream targets was analyzed at both the transcriptional (Fig. 3c and d) and translational (Fig. 3a and b) levels. In both cell lines, the expression of cyclin D1, VEGF, IGF-1, and IGF-1Rβ were found to decline in the combination-treated samples (Fig. 3).Fig. 3

Bottom Line: 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.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.Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. nipinsp@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus