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

Molecules

Kun-Hung Shen¹  Alex Chien-Hwa Liao¹  Jui-Hsiang Hung²  Wei-Jiunn Lee³  Kai-Chieh Hu²  Pin-Tsen Lin²  Ruei-Fang Liao² 

[1] Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan; E-Mails:;Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan; E-Mails:;Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; E-Mail:

关键词: α-solanine;    invasion;    EMT;    matrix metalloproteinase;    microRNA;   

DOI  :  10.3390/molecules190811896

来源: mdpi

【 摘 要 】

α-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 α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT). α-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 α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt and ERK. Moreover, α-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 α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-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 α-solanine for suppressing invasion of prostate cancer cell.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.