Halofuginone-induced autophagy suppresses the migration and invasion of MCF-7 cells via regulation of STMN1 and p53

氟吉诺酮诱导自噬通过调控STMN1和p53抑制MCF-7细胞迁移和侵袭

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作者:Xiaojing Xia, Lei Wang, Xiaojian Zhang, Shan Wang, Lianchen Lei, Likun Cheng, Yanzhao Xu, Yawei Sun, Bolin Hang, Gaiping Zhang, YueYu Bai, JianHe Hu

Abstract

Traditional Chinese medicines have been recognized as especially promising anticancer agents in modern anticancer research. Halofuginone (HF), an analog of quinazolinone alkaloid extracted from Dichroa febrifuga, is widely used in traditional medicine. However, whether HF inhibits the growth of breast cancer cells and/or reduces the migration and invasion of MCF-7 human breast cancer cells, as well as the underlying mechanisms in vitro, remains unclear. In this study, we report that an HF extract inhibits the growth of MCF-7 cells and reduces their migration and invasion, an important feature of potential anticancer agents. In addition, HF significantly increases the activation of autophagy, which is closely associated with tumor metastasis. As STMN1 and p53 have been closely implicated in breast cancer progression, we analyzed their expression in the context of HF extract treatment. Western blot analysis showed that HF suppresses STMN1 and p53 expression and activity in an autophagy-dependent manner. Collectively, these data indicate that activation of autophagy reduces expression of STMN1 and p53, and the migration and invasion of cancer cells contributes to the anti-cancer effects of the HF. These findings may provide new insight into breast cancer prevention and therapy.

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