The Potential Antioxidant Effects Of Ziziphus Jujube On Melanoma Cells

Year 2023, Volume: 13 Issue: 3, 2155 - 2161, 01.09.2023

Altuğ Küçükgül , Vesile Düzgüner , Mehmet Mustafa İşgör , Pınar Kızılkaya , Mustafa Cellat

https://doi.org/10.21597/jist.1244477

Abstract

Cellular redox homeostasis is compromised when exposed to internal or external stress factors, resulting in the superiority of the oxidant. It is known that these reactive oxygen species play a critical role in the etiology of many serious diseases like diabetes and cancer. Melanoma is the deadliest form of skin cancer and its rates are currently increasing faster than other preventable cancers. Melanoma is caused by the appearance of genetic mutations in pigment-producing cells, melanocytes. Ziziphus jujube Mill. spreads in regions of Asia with tropical/subtropical climates and has been used for thnds of years as basic traditional folk medicine. This study was carried out to determine the potential antioxidant effects of Ziziphus jujube on melanoma. Survival of cells was measured by MTT assay (colorimetric). Melanoma cells were treated three hours with 100% concentration Ziziphus jujube essential oil. Total antioxidant and oxidant capacity, glutathione, and nitric oxide levels were determined by spectrophotometrically. Ziziphus jujube prevented cell proliferation and increased total antioxidant capacity. Our results indicated that Ziziphus jujube inhibited the decrease in antioxidant levels and elevation of nitric oxide levels in melanoma cells. Also, the Ziziphus jujube administration improved GSH levels. Briefly, it can be concluded that Ziziphus jujube showed potential antioxidative and antiproliferative effects in melanoma cells. Recent research provides a detailed ethnopharmacological approach for the medicinal use of Ziziphus jujube fruit.

Keywords

Antioxidants, Melanoma, Oxidative stress, Ziziphus jujube

Thanks

ACKNOWLEDGEMENTS Cell culture studies of this research were performed at the Mustafa Kemal University Faculty of Veterinary.

Ziziphus Jujube'nin Melanom Hücreleri Üzerindeki Potansiyel Antioksidan Etkileri

Abstract

Hücresel redoks homeostazı, iç veya dış stres faktörlerine maruz kaldığında tehlikeye girerek oksidanların üstünlüğüne neden olur. Bu reaktif oksijen türlerinin diyabet ve kanser gibi birçok ciddi hastalığın etiyolojisinde kritik rol oynadığı bilinmektedir. Melanom, cilt kanserinin en ölümcül şeklidir ve oranları şu anda diğer önlenebilir kanserlerden daha hızlı artmaktadır. Melanom, pigment üreten hücreler olan melanositlerde genetik mutasyonların ortaya çıkmasından kaynaklanır. Ziziphus Jujube Mill., Asya'nın tropik/subtropikal iklime sahip bölgelerinde yetişir ve binlerce yıldır temel geleneksel halk ilacı olarak kullanılmaktadır. Bu çalışma, Ziziphus Jujube’nin melanom üzerindeki potansiyel antioksidan etkilerini belirlemek amacıyla yapılmıştır. Hücrelerin proliferasyonu, MTT analizi (kolorimetrik) ile ölçüldü. Melanom hücreleri, %100 konsantrasyonda Ziziphus Jujube esansiyel yağı ile üç saat muamele edildi. Total antioksidan ve oksidan kapasite, glutatyon ve nitrik oksit seviyeleri spektrofotometrik olarak belirlendi. Ziziphus Jujube, hücre çoğalmasını önlemiş ve toplam antioksidan kapasitesini artırmıştır. Sonuçlarımız, Ziziphus jujube'nin melanom hücrelerinde antioksidan seviyelerindeki düşüşü ve nitrik oksit seviyelerinin yükselmesini engellediğini göstermiştir. Ayrıca, Ziziphus Jujube uygulaması GSH düzeylerini iyileştirmiştir. Özetle, Ziziphus Jujube’nin melanom hücrelerinde potansiyel antioksidatif ve antiproliferatif etkiler gösterdiği sonucuna varılabilir. Son araştırmalar, Ziziphus Jujube meyvesinin tıbbi kullanımı için ayrıntılı bir etnofarmakolojik yaklaşım sunmaktadır.

Keywords

melanoma, ziziphus jujube, Antioksidanlar, Oksidatif stres

References

• Chen, J., Li, Z., Maiwulanjiang, M., Zhang, W. L., Zhan, J. Y., Lam, C. T., Zhu, K. Y., Yao, P., Choi, R. C., Lau, D. T., Dong, T. T., & Tsim, K. W. (2013). Chemical and biological assessment of Ziziphus jujuba fruits from China: different geographical sources and developmental stages. Journal of Agricultural and Food Chemistry, 61(30), 7315–7324.
• Chi, A., Kang, C., Zhang, Y., Tang, L., Guo, H., Li, H., & Zhang, K. (2015). Immunomodulating and antioxidant effects of polysaccharide conjugates from the fruits of Ziziphus Jujube on Chronic Fatigue Syndrome rats. Carbohydrate Polymers, 122, 189–196.
• Fuchs-Tarlovsky V. (2013). Role of antioxidants in cancer therapy. Nutrition (Burbank, Los Angeles County, Calif.), 29(1), 15–21.
• Gao, Q. H., Wu, C. S., & Wang, M. (2013). The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. Journal of Agricultural and Food Chemistry, 61(14), 3351–3363.
• Goyal, R., Sharma, P. L., & Singh, M. (2011). Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat. Journal of Natural Medicines, 65(3-4), 514–518.
• Hansen, M. B., Nielsen, S. E., & Berg, K. (1989). Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods, 119(2), 203–210.
• Hung, C. F., Hsu, B. Y., Chang, S. C., & Chen, B. H. (2012). Antiproliferation of melanoma cells by polysaccharide isolated from Zizyphus jujuba. Nutrition (Burbank, Los Angeles County, Calif.), 28(1), 98–105.
• Hürkan, Y.K. (2019). Hünnap (Ziziphus jujuba Mill.) Meyvesi: Geçmişten Günümüze Tıbbi Önemi. Journal of the Institute of Science and Technology, 9(3), 1271-1281.
• Kaeidi, A., Taati, M., Hajializadeh, Z., Jahandari, F., & Rashidipour, M. (2015). Aqueous extract of Zizyphus jujuba fruit attenuates glucose induced neurotoxicity in an in vitro model of diabetic neuropathy. Iranian Journal of Basic Medical Sciences, 18(3), 301–306.
• Kassi, E., Sourlingas, T. G., Spiliotaki, M., Papoutsi, Z., Pratsinis, H., Aligiannis, N., & Moutsatsou, P. (2009). Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Investigation, 27(7), 723–733.
• Manu, K. A., & Kuttan, G. (2008). Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells. International Immunopharmacology, 8(7), 974–981.
• Ottino, P., & Duncan, J. R. (1997). Effect of alpha-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells. Free Radical Biology & Medicine, 22(7), 1145–1151.
• Pahuja, M., Mehla, J., Reeta, K. H., Joshi, S., & Gupta, Y. K. (2011). Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Epilepsy & Behavior : E&B, 21(4), 356–363.
• Papageorgiou, M., Stiakaki, E., Dimitriou, H., Malliaraki, N., Notas, G., Castanas, E., & Kalmanti, M. (2005). Cancer chemotherapy reduces plasma total antioxidant capacity in children with malignancies. Leukemia Research, 29(1), 11–16.
• Patel, J. B., Shah, F. D., Shukla, S. N., Shah, P. M., & Patel, P. S. (2009). Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer. Journal of Cancer Research and Therapeutics, 5(4), 247–253.
• Preeti, & Tripathi, S., (2014). A phytopharmacological review on “Ziziphus jujuba”. International Journal of Research and Development in Pharmacy and Life Sciences, 3(3), 959-966.
• Rajopadhye, A., & Upadhye, A. S. (2016). Estimation of Bioactive Compound, Maslinic Acid by HPTLC, and Evaluation of Hepatoprotective Activity on Fruit Pulp of Ziziphus jujuba Mill. Cultivars in India. Evidence-Based Complementary and Alternative Medicine : eCAM, 2016, 4758734.
• Sammar, M., Abu-Farich, B., Rayan, I., Falah, M., & Rayan, A. (2019). Correlation between cytotoxicity in cancer cells and free radical-scavenging activity: In vitro evaluation of 57 medicinal and edible plant extracts. Oncology Letters, 18(6), 6563–6571.
• Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical Biochemistry, 25(1), 192–205.
• Siwak, D. R., Shishodia, S., Aggarwal, B. B., & Kurzrock, R. (2005). Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer, 104(4), 879–890.
• Volkovova, K., Bilanicova, D., Bartonova, A., Letašiová, S., & Dusinska, M. (2012). Associations between environmental factors and incidence of cutaneous melanoma. Review. Environmental Health : A Global Access Science Source, 11 Suppl 1(Suppl 1), S12.
• Yan, S. L., Huang, C. Y., Wu, S. T., & Yin, M. C. (2010). Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines. Toxicology In Vitro, 24(3), 842–848.
• Yue, Y., Wu, S., Zhang, H., Zhang, X., Niu, Y., Cao, X., Huang, F., & Ding, H. (2014). Characterization and hepatoprotective effect of polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp. Food and Chemical Toxicology, 74, 76–84.
• Zhang, W., Hong, D., Zhou, Y., Zhang, Y., Shen, Q., Li, J. Y., Hu, L. H., & Li, J. (2006). Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake. Biochimica et Biophysica Acta, 1760(10), 1505–1512.