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

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 investigate...

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Main Authors: Kun-Hung Shen, Alex Chien-Hwa Liao, Jui-Hsiang Hung, Wei-Jiunn Lee, Kai-Chieh Hu, Pin-Tsen Lin, Ruei-Fang Liao, Pin-Shern Chen
Format: Article
Language:English
Published: MDPI AG 2014-08-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/19/8/11896
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author Kun-Hung Shen
Alex Chien-Hwa Liao
Jui-Hsiang Hung
Wei-Jiunn Lee
Kai-Chieh Hu
Pin-Tsen Lin
Ruei-Fang Liao
Pin-Shern Chen
author_facet Kun-Hung Shen
Alex Chien-Hwa Liao
Jui-Hsiang Hung
Wei-Jiunn Lee
Kai-Chieh Hu
Pin-Tsen Lin
Ruei-Fang Liao
Pin-Shern Chen
author_sort Kun-Hung Shen
collection DOAJ
description 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.
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spelling doaj.art-0f2796714cb348e6899f26f82ecc41752022-12-21T18:59:32ZengMDPI AGMolecules1420-30492014-08-01198118961191410.3390/molecules190811896molecules190811896α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs ExpressionKun-Hung Shen0Alex Chien-Hwa Liao1Jui-Hsiang Hung2Wei-Jiunn Lee3Kai-Chieh Hu4Pin-Tsen Lin5Ruei-Fang Liao6Pin-Shern Chen7Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan 710, TaiwanDivision of Urology, Department of Surgery, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, TaiwanDepartment of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwanα-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.http://www.mdpi.com/1420-3049/19/8/11896α-solanineinvasionEMTmatrix metalloproteinasemicroRNA
spellingShingle Kun-Hung Shen
Alex Chien-Hwa Liao
Jui-Hsiang Hung
Wei-Jiunn Lee
Kai-Chieh Hu
Pin-Tsen Lin
Ruei-Fang Liao
Pin-Shern Chen
α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
Molecules
α-solanine
invasion
EMT
matrix metalloproteinase
microRNA
title α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
title_full α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
title_fullStr α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
title_full_unstemmed α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
title_short α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
title_sort α solanine inhibits invasion of human prostate cancer cell by suppressing epithelial mesenchymal transition and mmps expression
topic α-solanine
invasion
EMT
matrix metalloproteinase
microRNA
url http://www.mdpi.com/1420-3049/19/8/11896
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