.ALPHA.-Solanine Inhibits Human Melanoma Cell Migration and Invasion by Reducing Matrix Metalloproteinase-2/9 Activities

蛋白激酶B 化学 MAPK/ERK通路 PI3K/AKT/mTOR通路 癌症研究 磷酸化 基质金属蛋白酶 信号转导 细胞迁移 细胞生长 细胞凋亡 细胞生物学 细胞 分子生物学 生物 生物化学
作者
Ming-Kun Lu,Yuan‐Wei Shih,Tzu-Tsung Chang Chien,Li-Heng Fang,Hsiang-Ching Huang,Pin-Shern Chen
出处
期刊:Biological & Pharmaceutical Bulletin [Pharmaceutical Society of Japan]
卷期号:33 (10): 1685-1691 被引量:96
标识
DOI:10.1248/bpb.33.1685
摘要

α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.
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