title: Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells.
abstract: OBJECTIVE
  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.
authors: Institute of Experimental Medical Research, Department of Molecular Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Zeynep
authors: Z
authors: Birsu Cincin
authors: Miray
authors: M
authors: Unlu
authors: Bayram
authors: B
authors: Kiran
authors: Elif
authors: E
authors: Sinem Bireller
authors: Yusuf
authors: Y
authors: Baran
authors: Bedia
authors: B
authors: Cakmakoglu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D006569:Hesperidin