Nipin SP, Pramod Darvin, Young Beom Yoo, Youn Hee Joung, Dong Young Kang, Don Nam Kim, Tae Sook Hwang, Sang Yoon Kim, Wan Seop Kim, Hak Kyo Lee, Byung Wook Cho, Heui Soo Kim, Kyung Do Park, Jong Hwan Park, Soung Hoon Chang, and Young Mok Yang
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-1Rß, 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. [ABSTRACT FROM AUTHOR]