Novobiocin decreases SMYD3 expression and inhibits the migration of MDA-MB-231 human breast cancer cells.
SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase that plays an important role in transcriptional regulation in human carcinogenesis, and heat-shock protein HSP90A has been shown to increase the activity of SMYD3. We previously reported that overexpression of SMYD3 stimulated the migration of cells. In this study, we further found that novobiocin, a HSP90 inhibitor, could decrease the expression of SMYD3 and dose dependently inhibit the proliferation and migration of MDA-MB-231 human breast cancer cells. As a control, the short hairpin RNA (shRNA) targeting SMYD3 gene also showed similar effects with novobicin. This study is the first to show that novobiocin can inhibit the migration of breast cancer cells and such event may involve the downregulation of SMYD3. These findings might throw light on the development of novel therapeutic approaches to human cancers, and lend further understanding to the potential role of SMYD3 in human carcinogenesis.
Luo
Xue-Gang
XG
China Pharmaceutical University, Nanjing, China.
Zou
Jia-Ning
JN
Wang
Shu-Zhen
SZ
Zhang
Tong-Cun
TC
Xi
Tao
T
D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009675:Novobiocin / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics
D018841:HSP90 Heat-Shock Proteins; D034741:RNA, Small Interfering; D009675:Novobiocin; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human