Kitre Sakızının Farklı Kanser Hücreleri Üzerine Proliferatif Etkisi

Öz

Kitre sakızı (GT) Astragalus cinsinin Asyatik türlerinin dallarından ve gövdelerinden boşaltılan doğal bitki eksüdasıdır. Heterojen bir polisakkarit olan GT büyük biyouyumluluk, termal kararlılık, biyolojik olarak parçalanabilirlik, hidrofiliklik ve antioksidan aktivite gibi ayırt edici fizikokimyasal ve biyolojik özellikleri nedeniyle çeşitli biyomedikal alanlarda ve geleneksel olarak etnotıpta kullanılmaktadır. Bu çalışmada, GT’nin çeşitli kanser hücre dizileri üzerinde sitotoksik etkilerinin olup olmadığını araştırmayı amaçladık. Bu amaçla insan kolorektal adenokarsinomu (CACO-2), glioblastoma multiforma tümörü (T98G), yumurtalık sarkomu (SKOV-3) ve meme kanseri (MCF-7) hücreleri gibi dört farklı kanser hücre dizisi kullanıldı. GT, solvent olarak hem %5 DMSO hem de dH20 kullanılarak 200 µg/mL, 100 µg/mL, 50 µg/mL, 25 µg/mL ve 12.5 µg/mL konsantrasyonunda hazırlandı. İn vitro sitotoksisite çalışması için MTT (3-(4, 5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür) kolorimetrik deney kullanıldı. Hücre canlılığı yüzdeleri tüm uygulamalar için %80’in üzerinde bulunduğundan, GT’nin bu kanser hücreleri üzerinde sitotoksik etkisi olmadığı bulundu. Ancak, belirli konsantrasyonlarda GT’nin doza bağlı olarak dikkate değer hücre proliferasyonu etkinliği, MCF-7 dışındaki tüm kanser hücrelerinde gözlendi. Sonuç olarak, bu çalışma GT’nin kanser hücrelerinin proliferasyonunu arttırıcı etkisinden dolayı kanser hastalarının GT veya GT içeren ürünlerin kullanımı açısından dikkatli olunması gerektiğini önermektedir.

Anahtar Kelimeler

• Kitre sakızı
• Kanser hücresi
• Sitotoksisite
• MTT test
• Proliferasyon

Proliferative Effect of Gum Tragacanth on Different Cancer Cells

Öz

Gum tragacanth (GT) is a natural plant exudate discharged from the twigs and stems of Asiatic species of the Astragalus genus. GT is a heterogeneous polysaccharide which has been utilized in various biomedical fields and traditionally in ethnomedicine because of its distinctive physicochemical and biological properties, such as great biocompatibility, thermal stability biodegradability, hydrophilicity and antioxidant activity. The aim of this study was to examine whether GT has cytotoxic effects on various cancer cell lines. For this aim, four cancer cell lines i.e., human colorectal adenocarcinoma (CACO-2), glioblastoma multiforme tumor (T98G), ovarian sarcoma (SKOV-3), and breast cancer (MCF-7) cells were used. GT was prepared at the concentration of 200 µg/mL, 100 µg/mL, 50 µg/mL, 25 µg/mL and 12.5 µg/mL, using both 5% DMSO and dH2O as solvent. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was used for in vitro cytotoxicity study. GT had no cytotoxic effect on these cancer cells since cell viability percentages were found to be above 80% for all the treatments. However, remarkable dose-dependent cell proliferation efficiency of GT at certain concentrations was observed on all cancer cells except MCF-7. In conclusion, this study suggests that cancer patients should be careful about the use of GT or products containing GT due to the increasing effect of GT on the proliferation of cancer cells.

Anahtar Kelimeler

• Gum tragacanth (GT)
• Cancer cell
• Cytotoxicity
• MTT assay
• Cell proliferation

Kaynakça

1. Azarikia, F., & Abbasi, S. (2016). Mechanism of soluble complex formation of milk proteins with native gums (tragacanth and Persian gum). Food Hydrocolloids, 59, 35–44. https://doi.org/10.1016/j.foodhyd.2015.10.018
2. Balaghi, S., Mohammadifar, M. A., Zargaraan, A., Gavlighi, H. A., & Mohammadi, M. (2011). Compositional analysis and rheological characterization of gum tragacanth exudates from six species of Iranian Astragalus. Food Hydrocolloids, 25(7), 1775–1784. https://doi.org/10.1016/j.foodhyd.2011.04.003
3. Bertram, J. S. (2000). The molecular biology of cancer. Molecular Aspects of Medicine, 21(6), 167–223. https://doi.org/10.1016/S0098-2997(00)00007-8
4. Buranaamnuay, K. (2021). The MTT assay application to measure the viability of spermatozoa: A variety of the assay protocols. Open Veterinary Journal, 11(2), 251. https://doi.org/10.5455/OVJ.2021.v11.i2.9
5. Çınar, R., & Nazıroğlu, M. (2023). TRPM2 channel inhibition attenuates amyloid β42-induced apoptosis and oxidative stress in the hippocampus of mice. Cellular and Molecular Neurobiology, 43(3), 1335–1353. https://doi.org/10.1007/s10571-022-01253-0
6. Collins, T. F. X., Welsh, J. J., Black, T. N., Graham, S. L., & Brown, L. H. (1987). Study of the teratogenic potential of gum arabic. Food and Chemical Toxicology, 25(11), 815–821. https://doi.org/10.1016/0278-6915(87)90259-6
7. Dixit, K., Kulanthaivel, S., Agarwal, T., Pal, K., Giri, S., Maiti, T. K., & Banerjee, I. (2022). Gum tragacanth modified nano-hydroxyapatite: An angiogenic- osteogenic biomaterial for bone tissue engineering. Ceramics International, 48(10), 14672–14683. https://doi.org/10.1016/j.ceramint.2022.02.002
8. Fattahi, A., Petrini, P., Munarin, F., Shokoohinia, Y., Golozar, M. A., Varshosaz, J., & Tanzi, M. C. (2013). Polysaccharides derived from tragacanth as biocompatible polymers and gels. Journal of Applied Polymer Science, 129(4), 2092–2102. https://doi.org/10.1002/app.38931

9. Galbraith, W., Mayhew, E., Sugár, J., & Roe, E. M. F. (1963). Physical changes, measured by interference microscopy, in fresh landschütz ascites tumour cells after tragacanth and mannitol mustard treatments. British Journal of Cancer, 17(4), 738–744. https://doi.org/10.1038/bjc.1963.95
10. Gupta, V. K., Sood, S., Agarwal, S., Saini, A. K., & Pathania, D. (2018). Antioxidant activity and controlled drug delivery potential of tragacanth gum-cl- poly (lactic acid-co-itaconic acid) hydrogel. International Journal of Biological Macromolecules, 107, 2534–2543. https://doi.org/10.1016/j.ijbiomac.2017.10.138
11. Hagiwara, A., Tanaka, H., Tiwawech, D., Shirai, T., & Ito, N. (1991). Oral toxicity study of tragacanth gum in B6C3F1 mice: Development of squamous‐cell hyperplasia in the forestomach and its reversibility. Journal of Toxicology and Environmental Health, 34(2), 207–218. https://doi.org/10.1080/15287399109531560
12. Kandemir, S., & Ipek, P. (2023). Antiproliferative effect of Potentilla fulgens on glioblastoma cancer cells through downregulation of Akt/mTOR signaling pathway. Journal of Cancer Research and Therapeutics, 19,1818-1824. 0. https://doi.org/10.4103/jcrt.jcrt_1886_21
13. Kitchin, K. T., & Brown, J. L. (1989). Biochemical studies of promoters of carcinogenesis in rat liver. Teratogenesis, Carcinogenesis, and Mutagenesis, 9(5), 273–285. https://doi.org/10.1002/tcm.1770090503
14. López-García, J., Lehocký, M., Humpolíček, P., & Sáha, P. (2014). HaCaT keratinocytes response on antimicrobial atelocollagen substrates: Extent of cytotoxicity, cell viability and proliferation. Journal of Functional Biomaterials, 5(2), 43–57. https://doi.org/10.3390/jfb5020043
15. Maity, T., & Saxena, A. (2018). Use of hydrocolloids as cryoprotectant for frozen foods. Critical Reviews in Food Science and Nutrition, 58(3), 420-435. https://doi.org/10.1080/10408398.2016.1182892
16. Mohammadifar, M. A., Musavi, S. M., Kiumarsi, A., & Williams, P. A. (2006). Solution properties of targacanthin (water-soluble part of gum tragacanth exudate from Astragalus gossypinus). International Journal of Biological Macromolecules, 38(1), 31–39. https://doi.org/10.1016/j.ijbiomac.2005.12.015
17. Mosaddegh, M., Naghibi, F., Moazzeni, H., Pirani, A., & Esmaeili, S. (2012). Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran. Journal of Ethnopharmacology, 141(1), 80–95. https://doi.org/10.1016/j.jep.2012.02.004
18. Nazarzadeh Zare, E., Makvandi, P., & Tay, F. R. (2019). Recent progress in the industrial and biomedical applications of tragacanth gum: A review. Carbohydrate Polymers, 212, 450–467. https://doi.org/10.1016/j.carbpol.2019.02.076
19. Nejatian, M., Abbasi, S., & Azarikia, F. (2020). Gum Tragacanth: Structure, characteristics and applications in foods. International Journal of Biological Macromolecules, 160, 846–860. https://doi.org/10.1016/j.ijbiomac.2020.05.214
20. Nussinovitch, A. (2009). Plant gum exudates of the world: Sources, distribution, properties, and applications (1st ed.). CRC Press. https://doi.org/10.1201/9781420052244
21. Ranjbar-Mohammadi, M., Zamani, M., Prabhakaran, M. P., Bahrami, S. H., & Ramakrishna, S. (2016). Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration. Materials Science and Engineering: C, 58, 521–531. https://doi.org/10.1016/j.msec.2015.08.066
22. Saha, D., & Bhattacharya, S. (2010). Hydrocolloids as thickening and gelling agents in food: A critical review. Journal of Food Science and Technology, 47(6), 587–597. https://doi.org/10.1007/s13197-010-0162-6
23. Sayadnia, S., Arkan, E., Jahanban-Esfahlan, R., Sayadnia, S., & Jaymand, M. (2021). Thermal-responsive magnetic hydrogels based on Tragacanth gum for delivery of anticancer drugs. Journal of Polymer Research, 28(3), 90. https://doi.org/10.1007/s10965-020-02355-3
24. Sheorain, J., Mehra, M., Thakur, R., Grewal, S., & Kumari, S. (2019). In vitro anti-inflammatory and antioxidant potential of thymol loaded bipolymeric (tragacanth gum/chitosan) nanocarrier. International Journal of Biological Macromolecules, 125, 1069–1074. https://doi.org/10.1016/j.ijbiomac.2018.12.095
25. Taghavizadeh Yazdi, M., Nazarnezhad, S., Mousavi, S., Sadegh Amiri, M., Darroudi, M., Baino, F., & Kargozar, S. (2021). Gum Tragacanth (GT): A versatile biocompatible material beyond borders. Molecules, 26(6), 1510. https://doi.org/10.3390/molecules26061510
26. Verbeken, D., Dierckx, S., & Dewettinck, K. (2003). Exudate gums: Occurrence, production, and applications. Applied Microbiology and Biotechnology, 63(1), 10–21. https://doi.org/10.1007/s00253-003-1354-z
27. Verma, C., Negi, P., Pathania, D., Anjum, S., & Gupta, B. (2020). Novel tragacanth gum-entrapped lecithin nanogels for anticancer drug delivery. International Journal of Polymeric Materials and Polymeric Biomaterials, 69(9), 604–609. https://doi.org/10.1080/00914037.2019.1596910