title: α-Solanine inhibits invasion of human prostate cancer cell by suppressing epithelial-mesenchymal transition and MMPs expression.
abstract: 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.
authors.affiliation: Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan. robert.shen@msa.hinet.net.
authors.forename: Kun-Hung
authors.initials: KH
authors.lastname: Shen
authors.affiliation: Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan. ch159485@ms7.hinet.net.
authors.forename: Alex Chien-Hwa
authors.initials: AC
authors.lastname: Liao
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan. hung86@mail.chna.edu.tw.
authors.forename: Jui-Hsiang
authors.initials: JH
authors.lastname: Hung
authors.affiliation: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. lwj5905@gmail.com.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan. apple11763@yahoo.com.tw.
authors.forename: Kai-Chieh
authors.initials: KC
authors.lastname: Hu
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan. tina2572001@gmail.com.
authors.forename: Pin-Tsen
authors.initials: PT
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan. zeroadolz@gmail.com.
authors.forename: Ruei-Fang
authors.initials: RF
authors.lastname: Liao
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan. pschen@mail.chna.edu.tw.
authors.forename: Pin-Shern
authors.initials: PS
authors.lastname: Chen
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012992:Solanine / Q000008:administration & dosage*; D032324:Solanum nigrum / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
chemical_list: D015820:Cadherins; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C514919:alpha-solanine; D019716:Tissue Inhibitor of Metalloproteinase-2; D012992:Solanine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9