Apoptosis induced by Zizyphus jujuba seed essential oil in colorectal cancer cells line HT-29
Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)زهرا زمانی 1 , الهام قدوسی دهنوی 2 , رضا حاجی حسینی 3 , محمد ارجمند 4 , سیما نصری 5
1 - گروه بیوشیمی، انستیتو پاستور ایران، تهران، ایران;
2 - گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;
3 - گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;
4 - گروه بیوشیمی، انستیتو پاستور ایران، تهران، ایران;
5 - گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;
Keywords: Apoptosis, Colorectal cancer, Essential oil, Zizyphus jujuba seeds, p53, APC, KRAS,
Abstract :
Background & Aim: In traditional medicine, Zizyphus jujuba (jujube) has been used due to its medicinal properties and various physiological functions such as antioxidant, anticancer and anti-inflammatory properties. This study was conducted to study anti-cancer and apoptotic effects of essential oil from Zizyphus jujuba seeds and to evaluate the effect of essential oils on p53, APC and KRAS genes expression in HT-29 colorectal cell line.Experimental: In this study, the essential oil of jujube seeds collected from orchards in Isfahan was prepared by Clevenger apparatus and then analyzed by GC-MS. The effects of toxicity and cell viability were determined using Trypan Blue, MTT and clonogenic methods. DNA fragmentation and apoptosis techniques were used to evaluate the mechanism of the effects of essential oil on cell death by flow cytometry. Finally, Real-time PCR was used to evaluate the expression of p53, APC and KRAS genes and their role in induction of apoptosis.Results: Essential oil of Zizyphus jujuba seeds reduced the viability of cells by concentration and time-dependent manner as compared to the control group. The essential oil also induced apoptosis by increasing gene expression p53 and suppressing gene expression KRAS.Recommended applications/industries: The present results indicated that essential oil of Zizyphus jujuba seeds induces apoptosis by targeting genes involved in colon carcinogenesis. However, further investigations on signaling pathways are needed to fully confirm the results of this study.
Abraha, A. M. and Ketema, E. B. 2016. Apoptotic pathways as a therapeutic target for colorectal cancer treatment. World Journal of Gastrointestinal Oncology, 8(8): 583-591.
Adams, R. P. 2007. Identification of essential oil components by gas chromatography/mass spectrometry. Vol. 456. Carol Stream, IL: Allured publishing corporation. pp. 544-545.
Aiello, P., Sharghi, M., Mansourkhani, S. M., Ardekan, A. P., Jouybari, L., Daraei, N. and Kooti, W. 2019. Medicinal plants in the prevention and treatment of colon cancer. Oxidative Medicine and Cellular Longevity, 2019 (4): 5614-5664.
Al-Reza, S. M., Bajpai, V. K. and Kang, S. C. 2009. Antioxidant and antilisterial effect of seed essential oil and organic extracts from Zizyphus jujuba. Food and Chemical Toxicology, 47(9): 2374-2380.
Al-Reza, S. M., Rahman, A., Lee, J. and Kang, S. C. 2010a. Potential roles of essential oil and organic extracts of Zizyphus jujuba in inhibiting food-borne pathogens. Food Chemistry, 119(3): 981-986.
Al-Reza, S. M., Yoon, J. I., Kim, H. J., Kim, J. S. and Kang, S. C. 2010b. Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Food and Chemical Toxicology, 48(2): 639-643.
Andrade, M. A., Braga, M. A., Cesar, P. H., Trento, M. V. C., Espósito, M. A., Silva, L. F. and Marcussi, S. 2018. Anticancer properties of essential oils: an overview. Current Cancer Drug Targets, 18(10): 957-966.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. and Jemal, A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer Journal For Clinicians, 68(6): 394-424.
Crowley, L. C., Christensen, M. E. and Waterhouse, N. J. 2016. Measuring survival of adherent cells with the colony-forming assay. Cold Spring Harbor Protocols, 2016(8): 721-724.
Crowley, L. C., Marfell, B. J., Scott, A. P. and Waterhouse, N. J. 2016. Quantitation of apoptosis and necrosis by annexin V binding, propidium iodide uptake, and flow cytometry. Cold Spring Harbor Protocols, 2016(11): 953-957.
Dabaghian, F. H., Hassani, A., Nayeri, N., Shojaii, A. and Entezari, M. 2018. Anti-proliferative and apoptotic effects of aqueous extract of ziziphus jujube in human thyroid carcinoma cell lines (C643). International Journal of Cancer Management, 11(7): e65820.
Dai, Z. J., Gao, J., Ji, Z. Z., Wang, X. J., Ren, H. T., Liu, X. X. and Guan, H. T. 2009. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. Journal of Ethnopharmacology, 123(1): 91-96.
Ghodousi Dehnavi, E., Maghsoudi, H. and Haji Hosseini, R. 2018. Zizyphus jujuba seed essential oil inhibits lipopolysaccharide-stimulated THP-1 cells invasion and migration through suppression of matrix metalloproteinase-9 expression. Scientific Journal of Ilam University of Medical Sciences, 26: 197-209.
Green, M. R. and Sambrook, J. 2018. Quantification of RNA by Real-Time reverse transcription-polymerase chain reaction (RT-PCR). Cold Spring Harbor Protocols, 2018(10):1101-1110.
Green, M. R. and Sambrook, J. 2019. Analysis of DNA by agarose gel electrophoresis. Cold Spring Harbor Protocols, 2019(1): 1-3.
Huang, X., Kojima-Yuasa, A., Norikura, T., Kennedy, D. O., Hasuma, T. and Matsui-Yuasa, I. 2007. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. The American Journal Of Chinese Medicine, 35(03): 517-532.
Jaganathan, S. K. and Supriyanto, E. 2012. Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells. Molecules, 17(6): 6290-6304.
Jaganathan, S. K., Mazumdar, A., Mondhe, D. and Mandal, M. 2011. Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biology International, 35(6): 607-615.
Kawakami, H., Huang, S., Pal, K., Dutta, S. K., Mukhopadhyay, D. and Sinicrope, F. A. 2016. Mutant BRAF upregulates MCL-1 to confer apoptosis resistance that is reversed by MCL-1 antagonism and cobimetinib in colorectal cancer. Molecular Cancer Therapeutics, 15(12): 3015-3027.
Koosha, S., Mohamed, Z., Sinniah, A. and Alshawsh, M. A. 2019. Investigation into the molecular mechanisms underlying the anti-proliferative and anti-tumorigenesis activities of diosmetin against HCT-116 human colorectal cancer. Scientific Reports, 9(1): 1-17.
Li, L. B., Kim, Y. W., Wang, Y. H., Bai, L., Zhu, X. D., Zhao, Z. L. and Zhao, R. J. 2019. Methanol extract of semen Ziziphus Spinosae attenuates ethanol withdrawal anxiety by improving neuropeptide signaling in the central amygdala. BMC Complementary And Alternative Medicine, 19(1): 1-15.
Li, X. L., Zhou, J., Chen, Z. R. and Chang, W. J. 2015. P53 mutations in colorectal cancer-molecular pathogenesis and pharmacological reactivation. World Journal of Gastroenterology: WJG, 21(1): 84-93.
Majtnerová, P. and Roušar, T. 2018. An overview of apoptosis assays detecting DNA fragmentation. Molecular Biology Reports, 45(5): 1469-1478.
Mishra, T., Khullar, M. and Bhatia, A. 2011. Anticancer potential of aqueous ethanol seed extract of Ziziphus mauritiana against cancer cell lines and Ehrlich ascites carcinoma. Evidence-Based Complementary and Alternative Medicine, 2011(10): 40438-40447.
Taechakulwanijya, N., Weerapreeyakul, N., Barusrux, S. and Siriamornpun, S. 2013. Apoptosis induction effect of three jujube cultivars in HepG2 and Jurkat cell lines. International Journal of Bioscience, Biochemistry And Bioinformatics, 3(6): 540-544.
Taechakulwanijya, N., Weerapreeyakul, N., Barusrux, S. and Siriamornpun, S. 2016. Apoptosis-inducing effects of jujube (Zǎo) seed extracts on human Jurkat leukemia T cells. Chinese Medicine, 11(1): 1-13.
Tahergorabi, Z., Abedini, M. R., Mitra, M., Fard, M. H. and Beydokhti, H. 2015. Ziziphus jujuba: A red fruit with promising anticancer activities. Pharmacognosy Reviews, 9(18): 99-106.
Testa, U., Pelosi, E. and Castelli, G. 2018. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Medical Sciences, 6(2): 6290-6304.
Tuttolomondo, T., La Bella, S., Licata, M., Virga, G., Leto, C., Saija, A. and Ruberto, G. 2013. Biomolecular characterization of wild sicilian oregano: phytochemical screening of essential oils and extracts, and evaluation of their antioxidant activities. Chemistry and Biodiversity, 10(3): 411-433.
Vahedi, F., Najafi, M. F. and Bozari, K. 2008. Evaluation of inhibitory effect and apoptosis induction of Zizyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology, 56(2): 105-111.