Phytochemical analysis and antioxidant and anticancer activities of mastic gum resin from Pistacia atlantica subspecies kurdica

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 54.37.117.73 on 21-Dec-2018 For personal use only. Open Access Full Text Article Phytochemical analysis and antioxidant and anticancer activities of mastic gum resin from Pistacia atlantica subspecies kurdica This article was published in the following Dove Press journal: OncoTargets and Therapy Heshu Sulaiman Rahman 1–3 Department of Clinic and Internal Medicine, College of Veterinary Medicine, University of Sulaimani, Sulaimani, Kurdistan Region, Republic of Iraq; 2Department of Medical Laboratory Sciences, College of Science, Komar University of Science and Technology, ChaqChaq Qularaisee, Sarchinar District, Sulaimani, Kurdistan Region, Republic of Iraq; 3Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia 1 Correspondence: Heshu Sulaiman Rahman Animal Tissue Culture Laboratory, Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Tel +60 172 737512 Email Introduction Most recent data have shown that the number of cancer patients and mortality due to cancers are on the rise. Despite great advances in the development of new and innovative therapeutic strategies, cancer remains one of the leading causes of death.1 Although new cancer therapeutic and carcinostatic agents have been developed, their effects on cancer patients are generally not obvious. 4559 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2018:11 4559–4572 Dovepress © 2018 Rahman. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/OTT.S170827 Powered by TCPDF (www.tcpdf.org) Background: The mastic gum resin has been used in traditional Kurdish medicine for treating various disorders such as topical wound and gastric ulcer. The study designed to evaluate the total polyphenol and flavonoid content, free radical scavenging activity, and anticancer effects of mastic gum resin derived from Pistacia atlantica subspecies kurdica. Materials and methods: Folin -Ciocalteau and the aluminum chloride colorimetric assays were used to determine the total phenol and flavonoid contents in the mastic gum resin respectively. Whereas, DPPH and ABTS+ assays were used to determine the antioxidant activities of mastic gum resin. Regarding anticancer activities, the MTT assay was used to study the effect of mastic gum resin on the proliferation of various cancer cells and the morphological changes were identified after Acridine Orange/Propidium Iodide staining. Flow cytometry was applied to determine the influence of mastic gum resin on the apoptosis rate by Annexin V double staining and to investigate the influence on cell cycle progression. Caspase colorimetric assay was used to estimate the hallmark enzyme of apoptosis, and finally RNA were obtained from COLO205 cells and analyzed by qRT-PCR analyses. Results: The MTT results showed that the mastic gum resin at concentrations from 0.01 to 100 μM induced death of cancer cells in a dose and time-dependent manner. The mastic gum resin suppressed proliferation of human cancer cells with 72 h IC50 value of 15.34 ± 0.21, 11.52 ± 0.18, 8.11 ± 0.23 and 5.2 ± 0.8 μg/mL for bile duct cancer (cholangiocarcinoma) (KMBC), pancreatic carcinoma (PANC-1), gastric adenocarcinoma (CRL-1739), and colonic adenocarcinoma (COLO205) cells, respectively. Normal human colon fibroblast (CCD-18Co) cells were not adversely affected by resin treatment. Flow cytometry showed that the mastic gum resin significantly (P,0.05) arrested COLO205 cell proliferation at the G2/M phase of cell cycle. The resin caused apoptotic morphological changes in COLO205 cells. The apoptotic effect to mastic gum resin was via the mitochondrial as shown by the up-regulation of Bax, down-regulation of Bcl-2 genes, and activation of caspase-9 and -3 activities. Conclusion: It was confirmed that the antiproliferative efficacy of the resin is positively correlated with its polyphenolic contents, suggesting a causal link related to exudate content of phenolic acid and flavonoids. The results revealed that the mastic gum resin has potential to be developed as an anticancer and antioxidant product due to its high content of polyphenol compounds. Keywords: natural plant exudate, polyphenolic contents, free radical scavenging, apoptosis Dovepress OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 54.37.117.73 on 21-Dec-2018 For personal use only. Rahman In recent years, natural herbal metabolites have gained interest as compounds for alternative remedies for various diseases.2 According to the World Health Organization (WHO), almost 65% of the world’s population has included plants and traditional medicine as the additional modality in health care.3 In fact, several chemical compounds isolated from plants and traditional medicine have been shown to kill rapidly dividing cells,4 thus revealing their great potential to be developed as anticancer agents. However, the use of these compounds is limited by their narrow beneficial index, considerable toxicity, and delivery issues during treatment.5 The genus Pistacia belongs to a cosmopolitan family Anacardiaceae that comprises approximately 70 genera and more than 600 species.6 The species of the genus Pistacia are evergreen, aromatic, nutraceutical, and deciduous resinbearing shrubs and fast-growing xerophytic trees that can reach heights of 8–10 m.7 Pistacia plant parts including leaf, fruit, stem, exudate, and essential volatile oil have been chemically characterized and used to treat various human ailments8,9 because of their antiatherogenic,10 hypoglycemic,11 hepatoprotective,12 cytoprotective,13 antigenotoxic,14 antiinflammatory,15 antiulcerogenic,16 antipyretic, antifungal,17 antibacterial,18 antiviral,19 antiparasitic,20 antimutagenic,9 antioxidant,21 and anticancer activities,22–24 as well as stimulant and diuretic properties.25 The Pistacia atlantica subspecies kurdica, commonly known as Daraban or Qazwan tree in Kurdish26 and Baneh tree in Persian, is a medicinal and food plant that is native and endemic wild growing in Iran and in the Auramanat area of the Kurdist (...truncated)