Abstract
Casticin is one of the major active components isolated from Fructus viticis. Increasing studies have revealed that casticin has potential anticancer activity in various cancer cells, but its effects on breast cancer cell migration and invasion are still not well known. Therefore, the ability of cell migration and invasion in the breast cancer MDA-MB-231 and 4T1 cells treated by casticin was investigated. The results indicated that casticin significantly inhibited cell migration and invasion in the cells exposed to 0.25 and 0.50 µM of casticin for 24 h. Casticin treatment reduced matrix metalloproteinase (MMP) 9 (MMP-9) activity and down-regulated MMP-9 mRNA and protein expression, but not MMP-2. Casticin treatment suppressed the nuclear translocation of transcription factors c-Jun and c-Fos, but not nuclear factor-κB (NF-κB), and decreased the phosphorylated level of Akt (p-Akt). Additionally, the transfection of Akt overexpression vector to MDA-MB-231 and 4T1 cells could up-regulate MMP-9 expression concomitantly with a marked increase in cell invasion, but casticin treatment reduced Akt, p-Akt, and MMP-9 protein levels and inhibited the ability of cell invasion in breast cancer cells. Additionally, casticin attenuated lung metastasis of mouse 4T1 breast cancer cells in the mice and down-regulated MMP-9 expression in the lung tissues of mice treated by casticin. These findings suggest that MMP-9 expression suppression by casticin may act through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which in turn results in the inhibitory effects of casticin on cell migration and invasion in breast cancer cells. Therefore, casticin may have potential for use in the treatment of breast cancer invasion and metastasis.
Highlights
Breast cancer is the most frequently diagnosed cancer amongst women behind lung cancer [1]
The primary antibodies against matrix metalloproteinase (MMP)-2, MMP-9, nuclear factor-κB (NF-κB) P65, c-Jun, c-Fos, phosphatidylinositol 3-kinase (PI3K), Akt, phosphorylated level of Akt (p-Akt), P38, p-P38, c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), p-ERK, β-actin, and Lamin B were purchased from Cell Signal Technology (Beverly, MA, U.S.A.)
The quantitative results indicated that the invasive abilities of MDA-MB-231 and 4T1 were significantly reduced by casticin treatment compared with the control cells (Figure 2D)
Summary
Breast cancer is the most frequently diagnosed cancer amongst women behind lung cancer [1]. Cell migration and invasion are the key steps for breast cancer metastasis [4]. It has been shown that casticin has extensive anticancer pharmacological activities for various cancers including leukemia [6], ovarian cancer [7], colon cancer [8], lung cancer [5], hepatocellular carcinoma cells c 2018 The Author(s).
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