TY - JOUR T1 - Organ-specific antioxidant capacities and cytotoxic effects of Thermopsis turcica extracts in breast cancer AU - Terzi, Hakan AU - Yıldız, Mustafa AU - Yıldız, Saliha Handan AU - Albayrak, Fazilet Özlem AU - Karaosmanoğlu, Cem AU - Pehlivan, Emre AU - Aydın, Saliha PY - 2024 DA - April DO - 10.26650/IstanbulJPharm.2024.1354832 JF - İstanbul Journal of Pharmacy JO - iujp PB - Istanbul University WT - DergiPark SN - 2587-2087 SP - 80 EP - 88 VL - 54 IS - 1 LA - en AB - Background and Aims: Thermopsis turcica is an endemic species present in Türkiye and it is seen as a source of functional compounds such as antioxidant phenolics. Even though some biological activities of the aerial parts of T. turcica have been determined, knowledge regarding the organ-specific chemical composition and effects on human breast cancer is still scarce. Therefore, the present study aims to evaluate the antioxidant capacities, phenolic acid profiles, and potential biological activities of methanol extracts obtained from the leaf, flower, and stem tissues of T. turcica.Methods: The antioxidant capacities of methanol extracts of T. turcica was tested with complementary methods (TAC, CUPRAC, FRAP, and DPPH). While the total phenol (TPC) and flavonoid contents (TFC) of the extracts were determined spectrophotometrically, their phenolic acid profiles were determined by high-performance liquid chromatography (HPLC). The cytotoxic effects of extracts on the human normal breast cell line (MCF-10A cells) and the breast tumor cell lines (MCF7, MDA-MB-231, and SKBR3) were also analyzed after 24 h treatment.Results: The leaf extracts were found to have higher antioxidant capacity, which was associated with the presence of higher amounts of TPC and TFC. The HPLC analysis revealed the presence of quercetin, hesperidin, and rosmarinic acid as the main compounds in the leaf extracts, while a high amount of benzoic acid was found in the flower extract. Leaf and flower extracts also showed stronger cytotoxic activity against MCF-7 cells (IC50 values were 0.65 mg/mL and 0.55 mg/mL, respectively) as compared to stem extract (IC50 value was 1.10 mg/mL). Leaf extracts were the most active extract against SKBR3 cells with IC50 of 0.75 mg/mL. All extracts exhibited weak cytotoxic effects against MDA-MB-231 cells and IC50 values (1.53-1.75 mg/mL) were similar to the MCF-10A cells (IC50 values: 1.59-1.69 mg/mL).Conclusion: In conclusion, extracts derived from T. turcica have the potential to serve as a valuable source of bioactive metabolites with antioxidant and antiproliferative properties. KW - Antioxidant capacity KW - breast cancer KW - cytotoxic activity KW - phenolic content KW - Thermopsis turcica CR - Abotaleb, M., Liskova, A., Kubatka, P., & Büsselberg, D., (2020). Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules, 10(2), 221. https://doi.org/10.3390/biom10020221 google scholar CR - Aghababaei, F., & Hadidi, M. (2023). Recent advances in poten-tial health benefits of quercetin. Pharmaceuticals, 16(7), 1020. https://doi.org/10.3390/ph16071020 google scholar CR - Aksoy, L., Kolay, E., Ağılönü, Y., Aslan, Z., & Kargıoğlu, M. (2013). Free radical scavenging activity, total phenolic content, total an-tioxidant status, and total oxidant status of endemic Thermopsis turcica. Saudi Journal of Biological Sciences, 20(3), 235-239. https://doi.org/10.1016/j.sjbs.2013.02.003 google scholar CR - Apak, R., Güçlü, K., Demirata, B., Özyürek, M., Çelik, S. E., Bek-taşoğlu, B., . . . Özyurt, D. (2007). Comparative evaluation of various total antioxidant capacity assays applied to phenolic com-pounds with the CUPRAC assay. Molecules, 12, 1496-1547. https://doi.org/10.3390/12071496 google scholar CR - Bali, E. B., Açik, L., Akca, G., Sarper, M., Elçi, M. P., Avcu, F., & Vural, M. (2014). Antimicrobial activity against periodontopathogenic bacteria, antioxidant and cytotoxic ef-fects of various extracts from endemic Thermopsis turcica. Asian Pacific Journal of Tropical Biomedicine, 4(7), 505-514. https://doi.org/10.12980/APJTB.4.2014APJTB-2013-0010 google scholar CR - Cai, Y., Luo, Q., Sun, M., & Corke, H. (2004). Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sciences, 74, 2157-2184. https://doi.org/10.1016/j.lfs.2003.09.047 google scholar CR - Caponio, F., Alloggio, V., & Gomes, T. (1999). Phenolic compounds of virgin olive oil: influence of paste preparation techniques. Food Chemistry, 64, 203-209. https://doi.org/10.1016/S0308-8146(98)00146-0 google scholar CR - Cheynier, V. (2012). Phenolic compounds: from plants to foods. Phyto-chemistry Reviews, 11, 153-177. https://doi.org/10.1007/s11101-012-9242-8 google scholar CR - Çelik, Y., & Küçükkurt, İ. (2016). Investigation of the antiox-idant effects of extract obtained from Thermopsis turcica plant in rats. Kocatepe Veterinary Journal, 9(4), 259-265. https://dergipark.org.tr/en/pub/kvj/issue/32995/370465 google scholar CR - Deng, H., & van Verkel, G.J. (1998). Electrospray mass spectrometry and UV/visible spectrophotometry studies of aluminum (III)-flavonoid complex. Journal Mass Spec-trometry, 33, 1080-1087. https://doi.org/10.1002/(SICI)1096-9888(1998110)33:11 <1080::AID-JMS720>3.0.CO;2-2 google scholar CR - Elgadir, M. A., Chigurupati, S., & Mariod, A. A. (2023). Selected potential pharmaceutical and medical benefits of phenolic com-pounds: Recent advances. Functional Food Science, 3(7), 108. https://doi.org/10.31989/ffs.v3i7.1118 google scholar CR - Elshafie, H.S., Camele, I., & Mohamed, A.A. (2023). A com-prehensive review on the biological, agricultural and pharma-ceutical properties of secondary metabolites based-plant ori-gin. International Journal of Molecular Sciences, 24(4), 3266. https://doi.org/10.3390/yms24043266 google scholar CR - Espm, J. C., Soler-Rivas, C., & Wichers, H. J. (2000). Characteri-zation of the total free radical scavenger capacity of vegetable oils and oil fractions using 2,2-Diphenyl-1-picrylhydrazyl radi-cal. Journal of Agricultural and Food Chemistry, 48(3), 648-656. https://doi.org/10.1021/jf9908188 google scholar CR - Huang, D., Ou, B., & Prior, R. (2005). The chemistry behind antioxi-dant capacity assays. Journal of Agricultural and Food Chemistry, 53, 1841-1856. https://doi.org/10.1021/jf030723c google scholar CR - Ijaz, S., Iqbal, J., Abbasi, B.A., Ullah, Z., Yaseen, T., Kanwal, S., . . . Cho, W.C. (2023). Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications. Biomedicine & Pharmacotherapy, 162, 114687. https://doi.org/10.1016/j.biopha.2023.114687 google scholar CR - Kerneis, S., Swift, L.H., Lewis, C.W., Bruyere, C., Oumata, N., Colas, P., . . . Golsteyn, R.M. (2015). Natural prod-uct extracts of the Canadian prairie plant, Thermopsis rhombifolia, have anti-cancer activity in phenotypic cell-based assays, Natural Product Research, 29(11), 1026-1034, https://doi.org/10.1080/14786419.2014.979423 google scholar CR - Koc, B., Akyuz, L., Cakmak, Y.S., Sargin, I., Salaberria, A.M., Labidi, J., . . . Kaya, M. (2020). Production and characterization of chitosan-fungal extract films. Food Bioscience, 35, 100545, https://doi.org/10.1016/j.fbio.2020.100545 google scholar CR - Kumar, N., & Goel, N. (2019). Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnology Reports, 24, e00370. https://doi.org/10.1016/j.btre.2019.e00370 google scholar CR - Leicach, S.R., & Chludil, H.D. (2014). Plant secondary metabolites: structure-activity relationships in human health prevention and treatment of common diseases. In Atta-ur-Rahman (Ed.), Stud-ies in Natural Products Chemistry (pp. 267-270). Amsterdam,Elsevier. https://doi.org/10.1016/B978-0-444-63281-4.00009-4 google scholar CR - Lamuela-Raventos, R.M. (2018). Folin-Ciocalteu method for the measurement of total phenolic content and antioxidant ca-pacity. In R. Apak, E. Capanoglu & F. Shahidi (Eds.), Measurement of Antioxidant Activity & Capacity: Recent Trends and Applications (pp. 107-15.). New York, Wiley. https://doi.org/10.1002/9781119135388.ch6 google scholar CR - Liman, R., Eren, Y., Akyil, D., & Konuk, M. (2012). Determina-tion of mutagenic potencies of aqueous extracts of Thermopsis turcica by Ames test. Turkish Journal of Biology, 36, 85-92. https://doi.org/10.3906/biy-1011-158 google scholar CR - Lin, H. H., Chen, J. H., Chou, F. P., & Wang, C. J. (2011). Pro-tocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/NFkappaB pathway and MMP-2 production by targeting RhoB activation. Brazilian Journal of Pharmacology, 62(1), 237-254. https://doi.org/10.1111/j.1476-5381.2010.01022.x google scholar CR - Liu, H., Lee, J.I., & Ahn, T.G. (2019). Effect of quercetin on the anti-tumor activity of cisplatin in EMT6 breast tumor-bearing mice. Obstetrics & Gynecology Science, 62(4), 242-248. https://doi.org/10.5468/ogs.2019.62.4.242 google scholar CR - Lone, R., Baba, S.H., Khan, S., Al-Sadi, A.M., & Kamili, A.N. (2023). Phenolics: Key players in interaction between plants and their environment. In R Lone, S Khan & A Mohammed Al-Sadi (Eds.), Plant phenolics in abiotic stress management. Singapore, Springer. https://doi.org/10.1007/978-981-19-6426-8_2 google scholar CR - Madureira, M. B., Concato, V. M., Cruz, E. M. S., Bitencourt de Morais, . JM., Inoue, F. S. R., Concimo Santos, N., . . . Pavanelli, W.R. (2023). Naringenin and hesperidin as promising alternatives for prevention and co-adjuvant therapy for breast cancer. Antioxi-dants, 12(3), 586. https://doi.org/10.3390/antiox12030586 google scholar CR - Manzoor, A., Yousuf, B., Pandith, J. A., & Ahmad, S. (2023). Plant-derived active substances incorporated as antioxidant, antibacterial or antifungal components in coatings/films for food packaging applications. Food Bioscience, 53, 102717. https://doi.org/10.1016/j.fbio.2023.102717 google scholar CR - Molole, G.J., Gure, A., & Abdissa, N. (2022). Determination of total phenolic content and antioxidant activity of Com-miphora mollis (Oliv.) Engl. Resin. BMC Chemistry, 16, 48. https://doi.org/10.1186/s13065-022-00841-x google scholar CR - Muhammad, T., Ikram, M., Ullah, R., Rehman, S.U., & Kim, M.O. (2019). Hesperetin, a Citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4/NF-kB signaling. Nutrients, 11 (3), 648. https://doi.org/10.3390/nu11030648 google scholar CR - Önder, G. Ö., Göktepe, Ö., Baran, M., Bitgen, N., Aydın, F., & Yay, A. (2023). Therapeutic potential of hesperidin: Apoptosis induction in breast cancer cell lines. Food and Chemical Toxicology, 176, 113791. https://doi.org/10.1016/j.fct.2023.113791 google scholar CR - Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31.https://doi.org/10.1016/j.nutres.2021.05.011 google scholar CR - Prieto, P., Pineda, M., & Aguilar, M. (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the deter-mination of vitamin E. Analytical Biochemistry, 269, 337-341. http://dx.doi.org/10.1006/abio.1999.4019 google scholar CR - Ranganathan, S., Halagowder, D., & Sivasithambaram, N.D. (2015). Quercetin suppresses twist to induce apoptosis in MCF-7 breast cancer cells. PLoS One, 10(10), e0141370. https://doi.org/10.1371/journal.pone.0141370 google scholar CR - Salmeron-Manzano, E., Garrido-Cardenas, J. A., & Manzano-Agugliaro, F. (2020). Worldwide research trends on medicinal plants. International Journal of Environmental Research and Pub-lic Health, 17, 3376. https://doi.org/10.3390/yerph17103376 google scholar CR - Sinan, K.I., Yagi, S., Llorent-Martmez, E.J., Ruiz-Medina, A., Gordo-Moreno, A.I., Stefanucci, A., . . . Zengin, G. (2023). Understand-ing the chemical composition and biological activities of differ-ent extracts of Secamone afzelii leaves: A potential source of bioactive compounds for the food industry. Molecules, 28, 3678. https://doi.org/10.3390/molecules28093678 google scholar CR - Singleton, V. L. & Rossi, J. A. (1965). Colorimetry of total phe-nolics with phosphomolybdic-phosphotungstic acid reagents. American Journal of Enology and Viticulture, 16, 144—158. https://doi.org/10.5344/ajev.1965.16.3.144 google scholar CR - Tan, K., Vural, M., & Küçüködük, M. (1983). An unusual new Ther-mopsis from Turkey. Notes from the Royal Botanic Garden of Edinburgh, 40, 515-518. google scholar CR - Tuberoso, C.I.G., Rosa, A., Bifulco, E., Melis, M.P., Atzeri, A., Pirisi, F.M., & Dessi, M.A. (2010) Chemical com-position and antioxidant activities of Myrtus commu-nis L. berries extracts. Food Chemistry, 123, 1242-1251. https://doi.org/10.1016/j.foodchem.2010.05.094 google scholar CR - Tuescher, J. M., Tailfeathers, D., Kerneis, S. M., Baratte, B., Ruchaud, S., Bach, S., . . . Golsteyn, R.M. (2020). The Canadian prairie plant Thermopsis rhombifolia contains luteolin, a flavone that in-hibits cyclin dependent kinase 9 and arrest cells in the G1-phase of the cell cycle. Journal of Natural Health Product Research, 2(2), 1-14. https://doi.org/10.33211/jnhpr.12 google scholar CR - Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T.D., Mazur, M., & Telser, J. (2007). Free radicals and antioxidants in normal physiological functions and human disease. The Inter-national Journal of Biochemistry & Cell Biology, 39, 4484. https://doi.org/10.1016/j.biocel.2006.07.001 google scholar CR - Wang, Y. J., Wang, F., Yu, L. X., Xiang, Y. J., Zhou, F., Huang, S.Y., . . . Liu, L.Y. (2022). Worldwide review with meta-analysis of women’s awareness about breast can-cer. Patient Education and Counseling, 105(7), 1818-1827. https://doi.org/10.1016/j.pec.2021.12.012 google scholar CR - Wojciechowski, M. F. (2003). Reconstructing the phylogeny of legumes (Leguminosae): an early 21st century perspective. In BB Klitgaard & A Bruneau (Eds.), Advances in Legume Systematics, Part 10, Higher Level Systematics (pp. 5-35). Kew, UK: Royal Botanic Gardens. google scholar CR - Xu, D.-P., Li, Y., Meng, X., Zhou, T., Zhou, Y., Zheng, J., . . . Li, H.-B. (2017). Natural antioxidants in foods and medicinal plants: extrac-tion, assessment and resources. International Journal of Molecu-lar Sciences, 18(1), E96. https://doi.org/10.3390/yms18010096 google scholar CR - Yıldız, M., Terzi, H., Yıldız, S. H., Varol, N., Özdemir Erdoğan, M., Kasap, M., . . . Solak, M. (2020). Proteomic analysis of the anti-cancer effect of various extracts of endemic Thermopsis turcica in human cervical cancer cells. Turkish Journal of Medical Sciences, 50(8), 1993-2004. https://doi.org/10.3906/sag-2005-321 google scholar CR - Zhang, P., Zou, J. B., An, Q., Yi, P., Yuan, C. M., Huang, L. J., . . . Hao, X. J. (2022). Two new cytisine-type al-kaloids from the seeds of Thermopsis lanceolata. Journal of Asian Natural Products Research, 24(12), 1141-1149. https://doi.org/10.1080/10286020.2021.2020759 google scholar UR - https://doi.org/10.26650/IstanbulJPharm.2024.1354832 L1 - https://dergipark.org.tr/en/download/article-file/3383767 ER -