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Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells

Authors Ye T, Su J, Huang C, Yu D, Dai S, Huang X, Chen B, Zhou M

Received 18 September 2016

Accepted for publication 8 November 2016

Published 12 December 2016 Volume 2016:9 Pages 7481—7492

DOI https://doi.org/10.2147/OTT.S122653

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Dr XuYu Yang


Tingting Ye,1 Jiadong Su,1 Chaohao Huang,1 Dinglai Yu,1 Shengjie Dai,1 Xince Huang,1 Bicheng Chen,1,2 Mengtao Zhou1

1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China

Abstract:
Isoorientin (or homoorientin) is a flavone, which is a chemical flavonoid-like compound, and a 6-C-glucoside of luteolin. Isoorientin has been demonstrated to have anti-cancer activities against various tumors, but its effects on pancreatic cancer (PC) have not been studied in detail. In this study, we aim to investigate whether isoorientin has potential anti-PC effects and its underlying mechanism. In PC, isoorientin strongly inhibited the survival of the cells, induced cell apoptosis, and decreased its malignancy by reversing the expression of epithelial–mesenchymal transition and matrix metalloproteinase and decreased vascular endothelial growth factor expression. Meanwhile, we investigated the activity of the AMP-activated protein kinase (AMPK) signaling pathway after isoorientin treatment, which was forcefully activated by isoorientin, as expected. In addition, in the PC cells that were transfected with lentivirus to interfere with the expression of the gene PRKAA1, there were no differences in the apoptosis rate and the expression of malignancy biomarkers in the tumors of the isoorientin-treated and untreated groups. Thus, we demonstrated that isoorientin has potential antitumor effects via the AMPK signaling pathway, and isoorientin merits further investigation.

Keywords: pancreatic cancer, AMPK, isoorientin, apoptosis, invasiveness, VEGF

Corrigendum for this paper has been published

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