alpha-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression

作者：Shen Kun Hung; Liao Alex Chien Hwa; Hung Jui Hsiang; Lee Wei Jiunn; Hu Kai Chieh; Lin Pin Tsen; Liao Ruei Fang; Chen Pin Shern^*

来源：Molecules, 2014, 19(8): 11896-11914.

DOI：10.3390/molecules190811896

• alpha-solanine
• invasion
• EMT
• matrix metalloproteinase
• microRNA

alpha-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by alpha-solanine remains unclear. This study investigates the suppression mechanism of alpha-solanine on motility of the human prostate cancer cell PC-3. Results show that alpha-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of alpha-solanine, cell invasion is markedly suppressed by alpha-solanine. alpha-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT). alpha-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate alpha-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt and ERK. Moreover, alpha-solanine downregulates oncogenic microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by alpha-solanine may be, at least in part, through blocking EMT and MMPs expression. alpha-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of alpha-solanine for suppressing invasion of prostate cancer cell.

• 出版日期2014-8