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Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma.
Chem Biol Interact. 2019 Jul 01; 307:158-166.CB

Abstract

Metastatic osteosarcoma usually has an unsatisfactory response to the current standard chemotherapy and causes poor prognosis. Currently, epithelial-mesenchymal transition (EMT) is reported as a critical event in osteosarcoma metastasis. Glaucocalyxin A, a bioactive ent-kauranoid diterpenoid, exerts anti-cancer effect on osteosarcoma by inducing apoptosis in previous study. However, the effect of Glaucocalyxin A on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the potential mechanisms of Glaucocalyxin A on EMT and metastasis of osteosarcoma. We found that Glaucocalyxin A inhibited migration and invasion of MG-63 and 143B cells. Moreover, Glaucocalyxin A increased the protein and mRNA levels of E-cadherin and decreased the protein and transcription expression of N-cadherin, Vimentin. Glaucocalyxin A also inhibited the protein and mRNA levels of EMT-associated transcription factor including Snail and Slug. Furthermore, Glaucocalyxin A inhibited transforming growth factor-β1 (TGF-β1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-β-induced phosphorylation of Smad 2/3 in osteosarcoma U2OS cells. Finally, we established transplanted metastatic models of highly metastatic osteosarcoma 143B cells. Glaucocalyxin A inhibited lung metastasis in vivo. Interestingly, Glaucocalyxin A increased the protein expression of E-cadherin and reduced the protein expression of N-cadherin and Vimentin. Glaucocalyxin A inhibited the protein expression of Snail and Slug in vivo. In summary, this study demonstrated that Glaucocalyxin A inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma.

Authors+Show Affiliations

School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.The First Clinical Medical College, Nanjing Medical University, 101Longmian Avenue, Jiangning District, Nanjing 211166, People's Republic of China.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China. Electronic address: sunyangsunny@njtech.edu.cn.School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China. Electronic address: zhangqi@njtech.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31059706

Citation

Jiang, Xiubo, et al. "Glaucocalyxin a Reverses EMT and TGF-β1-induced EMT By Inhibiting TGF-β1/Smad2/3 Signaling Pathway in Osteosarcoma." Chemico-biological Interactions, vol. 307, 2019, pp. 158-166.
Jiang X, Zhang Z, Song C, et al. Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Chem Biol Interact. 2019;307:158-166.
Jiang, X., Zhang, Z., Song, C., Deng, H., Yang, R., Zhou, L., Sun, Y., & Zhang, Q. (2019). Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Chemico-biological Interactions, 307, 158-166. https://doi.org/10.1016/j.cbi.2019.05.005
Jiang X, et al. Glaucocalyxin a Reverses EMT and TGF-β1-induced EMT By Inhibiting TGF-β1/Smad2/3 Signaling Pathway in Osteosarcoma. Chem Biol Interact. 2019 Jul 1;307:158-166. PubMed PMID: 31059706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. AU - Jiang,Xiubo, AU - Zhang,Zhenhao, AU - Song,Changqin, AU - Deng,Hanzhi, AU - Yang,Runyu, AU - Zhou,Lvqi, AU - Sun,Yang, AU - Zhang,Qi, Y1 - 2019/05/04/ PY - 2018/12/10/received PY - 2019/04/27/revised PY - 2019/05/03/accepted PY - 2019/5/7/pubmed PY - 2019/6/27/medline PY - 2019/5/7/entrez KW - Epithelial-mesenchymal transition (EMT) KW - Glaucocalyxin A KW - Osteosarcoma KW - Smad KW - Transforming growth factor-β1 (TGF-β1) SP - 158 EP - 166 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 307 N2 - Metastatic osteosarcoma usually has an unsatisfactory response to the current standard chemotherapy and causes poor prognosis. Currently, epithelial-mesenchymal transition (EMT) is reported as a critical event in osteosarcoma metastasis. Glaucocalyxin A, a bioactive ent-kauranoid diterpenoid, exerts anti-cancer effect on osteosarcoma by inducing apoptosis in previous study. However, the effect of Glaucocalyxin A on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the potential mechanisms of Glaucocalyxin A on EMT and metastasis of osteosarcoma. We found that Glaucocalyxin A inhibited migration and invasion of MG-63 and 143B cells. Moreover, Glaucocalyxin A increased the protein and mRNA levels of E-cadherin and decreased the protein and transcription expression of N-cadherin, Vimentin. Glaucocalyxin A also inhibited the protein and mRNA levels of EMT-associated transcription factor including Snail and Slug. Furthermore, Glaucocalyxin A inhibited transforming growth factor-β1 (TGF-β1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-β-induced phosphorylation of Smad 2/3 in osteosarcoma U2OS cells. Finally, we established transplanted metastatic models of highly metastatic osteosarcoma 143B cells. Glaucocalyxin A inhibited lung metastasis in vivo. Interestingly, Glaucocalyxin A increased the protein expression of E-cadherin and reduced the protein expression of N-cadherin and Vimentin. Glaucocalyxin A inhibited the protein expression of Snail and Slug in vivo. In summary, this study demonstrated that Glaucocalyxin A inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/31059706/Glaucocalyxin_A_reverses_EMT_and_TGF_β1_induced_EMT_by_inhibiting_TGF_β1/Smad2/3_signaling_pathway_in_osteosarcoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(18)31718-6 DB - PRIME DP - Unbound Medicine ER -