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Cellular Oncology
Published in: Cellular Oncology 3/2015

01-06-2015 | Original Paper

Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells

Authors: Zeynep Birsu Cincin, Miray Unlu, Bayram Kiran, Elif Sinem Bireller, Yusuf Baran, Bedia Cakmakoglu

Published in: Cellular Oncology | Issue 3/2015

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Abstract

Purpose

Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved.

Methods

The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA).

Results

We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells.

Conclusions

Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
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Metadata
Title
Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells
Authors
Zeynep Birsu Cincin
Miray Unlu
Bayram Kiran
Elif Sinem Bireller
Yusuf Baran
Bedia Cakmakoglu
Publication date
01-06-2015
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 3/2015
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0222-z

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