Neda Roshanravan
1 
, Parina Asgharian
2,3 , Hassan Dariushnejad
4 , Naimeh Mesri Alamdari
5 , Behzad Mansoori
6 , Ali Mohammadi
6 , Shahriar Alipour
7 , Meisam Barati
8 , Abed Ghavami
9 , Vajihe Ghorbanzadeh
10 , Fatemeh Aamazadeh
9 , Alireza Ostadrahimi
9* 1 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Pharmacognosy, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
5 Students Research Committee, School of Health, Iran University of Medical Science, Tehran, Iran.
6 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
7 Department of Molecular Medicine, Connective Tissue Disease Research Center, Tabriz University of Medical Sciences, Tabriz,Iran.
8 Students Research Committee, Cellular and Molecular Nutrition Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
9 Nutrition Research Center, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran.
10 Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
Abstract
Purpose: Pancreatic adenocarcinoma has a high prevalence all over the world. Most of the therapeutic approaches failed as a result of tumor invasion and rapid metastasis. Several natural plants have been shown to have promising therapeutic effects. Thus, the aim of this study was to investigate the cytotoxic activity of Eryngium billardieri against PANC-1 cancer cell lines. Methods: Dimethylthiazole diphenyltetrazolium bromide assay (MTT assay) and flow cytometry were used to assess the cytotoxicity of E. billardieri extracts against PANC-1 cancer cell lines. Quantitative Polymerase Chain Reaction (qPCR) was conducted to investigate the expression levels of Bcl2- associated X protein (BAX) and cyclin D1. Results: The results of the MTT assay showed that E. billardieri extracts had cytotoxic effects on PANC- 1 cancer cell lines. Moreover, the findings from the gene expression confirmed the over expression of Bax, and under expression of cyclin D1 following treatment with dichloromethane (DCM) and n-hexane (n- hex) extracts in cancer cells (P < 0.05). Interestingly, the flow cytometry results showed that DCM and n- hex extracts of E. billardieri induced apoptosis in PANC- 1 cancer cell lines. Conclusion: The results of this study demonstrated that DCM and n- hex extracts of E. billardieri significantly induce apoptosis by increasing Bax and decreasing cyclin D1 mRNA expression. Therefore, E. billardieri may be regarded as a novel approach for treatment of pancreatic cancer as a result of its promising apoptotic and cytotoxic properties.