Roghiyeh Pashaei-Asl
1,2, Fatima Pashaei-Asl
3, Parvin Mostafa Gharabaghi
4*, Khodadad Khodadadi
5, Mansour Ebrahimi
6, Esmaeil Ebrahimie
7,8,9,10, Maryam Pashaiasl
4,11,12*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.
*Corresponding Author: Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Iran. Email pm_gharabaghi@yahoo.com, pashaim@tbzmed.ac.ir
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.