Casticin inhibits breast cancer cell migration and invasion by down-regulation of PI3K/Akt signaling pathway

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.

Next‑generation sequencing analysis reveals that MTH‑3, a novel curcuminoid derivative, suppresses the invasion of MDA‑MB‑231 triple‑negative breast adenocarcinoma cells

“…The results of the present study showed that MTH-3 inhibits MDA-MB-231 cell invasion and migration by decreasing the activity of MMP-9, instead of that of MMP-2. These results were consistent with those reported by Fan et al (43), who demonstrated that casticin inhibits MMP-9 protein expression and activity in breast cancer cells.…”

Berberine Inhibits MDA-MB-231 Cells by Attenuating Their Inflammatory Responses

“…And based on the finding, we explored the possible mechanism in several ways, such as inflammation-related signaling pathway and early response genes. The c-fos and c-jun signaling pathway has been studied for many years of their role in the cell migration [16,17]. In the present study, we found that scratching caused increased protein expression levels of these two proteins, which could be inhibited by the berberine treatment.…”

An Overview of the Potential Antineoplastic Effects of Casticin

“…Breast cancer is the most prevalent type of cancer in women and is a major cause of mortality worldwide due to its poor prognosis and diagnostic procedures [49][50][51][52]. Pretreatment of casticin on MDA-MB-231 and 4T1 cells resulted in downregulation of MMP-9 mRNA protein expression but has no significant effect on MMP-2, suggesting that casticin can suppress both migration and invasion abilities in breast cancer cells.…”