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Adv Pharm Bull. 2017 Jun;7(2):241-249. doi: 10.15171/apb.2017.029. Epub 2017 Jun 30.

The Inhibitory Effect of Ginger Extract on Ovarian Cancer Cell Line; Application of Systems Biology.

Author information

1
Department of Anatomy, Medical School, Iran University of Medical Science, Tehran, Iran.
2
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
3
Molecular Biology Laboratory, Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4
Women's Reproductive Health Research Center, Tabriz University of Medical Sciences Tabriz, Iran.
5
Genetic Research Theme, Murdoch Children's Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, Australia.
6
Department of Biology, University of Qom, Qom, Iran.
7
Institute of Biotechnology, Shiraz University, Shiraz, Iran.
8
School of Biological Sciences, Faculty of Science and Engineering, Flinders University, Adelaide, Australia.
9
School of Information Technology and Mathematical Sciences, Division of Information Technology, Engineering and the Environment, The University of South Australia, Adelaide, Australia.
10
School of Animal & Veterinary Science, The University of Adelaide, Australia.
11
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
12
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Iran.

Abstract

Purpose: Ginger is a natural compound with anti-cancer properties. The effects of ginger and its mechanism on ovarian cancer and its cell line model, SKOV-3, are unclear. In this study, we have evaluated the effect of ginger extract on SKOV-3. Methods: SKOV-3 cells were incubated with ginger extract for 24, 48 and 72 hours. Cell toxicity assay was performed. Different data mining algorithms were applied to highlight the most important features contributing to ginger inhibition on the SKOV-3 cell proliferation. Moreover, Real-Time PCR was performed to assay p53, p21 and bcl-2 genes expression. For co-expression meta-analysis of p53, mutual ranking (MR) index and transformation to Z-values (Z distribution) were applied on available transcriptome data in NCBI GEO data repository. Results: The ginger extract significantly inhibited cancer growth in ovarian cancer cell line. The most important attribute was 60 µg/ml concentration which received weights higher than 0.50, 0.75 and 0.95 by 90%, 80% and 50% of feature selection models, respectively. The expression level of p53 was increased sharply in response to ginger treatment. Systems biology analysis and meta-analysis of deposited expression value in NCBI based on rank of correlation and Z-transformation approach unraveled the key co-expressed genes and co-expressed network of P53, as the key transcription factor induced by ginger extract. High co-expression between P53 and the other apoptosis-inducing proteins such as CASP2 and DEDD was noticeable, suggesting the molecular mechanism underpinning of ginger action. Conclusion: We found that the ginger extract has anticancer properties through p53 pathway to induce apoptosis.

KEYWORDS:

Anticancer; Bcl-2; Ginger extract; Meta-analysis ; Ovarian cancer; P53; Systems biology analysis

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