Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Pinitol suppresses tumor necrosis factor-alpha-induced invasion of prostate cancer LNCaP cells by inhibiting nuclear factor-kB-mediated matrix metalloproteinase-9 expression

Rajapaksha Gedara Prasad Tharanga Jayasooriya¹, Chang-Hee Kang¹, Sang Rul Park¹, Yung-Hyun Choi², Gi-Young Kim¹

¹Department of Marine Life Sciences, Jeju National University, Jeju 690-756; ²Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-054, Republic of Korea.

For correspondence:- Gi-Young Kim Email: immunkim@jejunu.ac.kr Tel:+82647543427

Received: 4 May 2015 Accepted: 10 June 2015 Published: 30 August 2015

Citation: Jayasooriya RG, Kang C, Park SR, Choi Y, Kim G. Pinitol suppresses tumor necrosis factor-alpha-induced invasion of prostate cancer LNCaP cells by inhibiting nuclear factor-kB-mediated matrix metalloproteinase-9 expression. Trop J Pharm Res 2015; 14(8):1357-1364 doi: 10.4314/tjpr.v14i8.6

© 2015 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the mechanism by which pinitol inhibits tumor necrosis factor-α (TNF-α)-induced expression of matrix metalloproteinase-9 (MMP-9) and invasion of prostate cancer LNCaP cells.

Methods: Reverse transcription-polymerase chain reaction (RT-PCR) together with Western blot analysis was used to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, in TNF-α-treated LNCaP cells, while 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and DNA fragmentation were used to evaluate cell viability and apoptosis. MMP-9 activity and invasion were measured by gelatin zymography and matrigel invasion assay, respectively. DNA-binding activity of NF-κB and AP-1 was determined by electrophoretic mobility shift assay and luciferase activity.

Results: MMP-9 activity significantly increased in response to TNF-α; however, pinitol reduced TNF-α-induced MMP-9 activity without cytotoxicity. Matrigel invasion assay showed that pinitol reduced TNF-α-induced invasion of prostate cancer LNCaP cells. Further, it downregulated the expression of MMP-9 gene induced by TNF-α-treatment. Pinitol suppressed TNF-α-induced NF-κB activity by suppressing nuclear translocation of the NF-κB subunits, p65 and p50.

Conclusion: The results indicate that pinitol is a potential anti-invasive agent and acts by suppressing TNF-α-induced cancer cell invasion and specifically inhibiting NF-κB as well as downstream target genes such as MMP-9.

Keywords: Pinitol, Matrix metalloproteinase-9, Cell invasion, Nuclear factor, Nuclear translocation