Effects of Pervari Honey from Türkiye on Proliferation, Oxidative Stress, and Apoptosis of Human Breast Cancer Cells

Year 2024, Volume: 10 Issue: 3, 627 - 639, 30.09.2024

Muazzez Derya Andeden , Pınar Altın Çelik , Mustafa Çakır , Ramazan Üzen , Hamiyet Altuntaş

https://doi.org/10.28979/jarnas.1456528

Abstract

Breast cancer is one of the most common causes of deaths worldwide. Major obstacles to treatment have contributed to the increasing popularity of complementary or alternative therapies. Although recent results support the mechanism that honey induces cell death, the full mechanisms are still unknown. This study investigates the potential use of Pervari honey (PH) as an in vitro therapeutic agent in breast cancer. Firstly, the antioxidant capacity and total phenolic content of PH were tested. In addition, MCF-7 and MDA-MB-231 breast cancer cells treated with PH were examined for cell viability, reactive oxygen species production, oxidative deoxyribonucleic acid (DNA) damage, and apoptosis. Our results show that PH treatment decreased cell viability dose-dependently and increased reactive oxygen species (ROS) levels, oxidative DNA damage, and apoptosis rate. The present study suggests that honey is a promising source to produce pharmaceuticals and nutraceuticals for breast cancer therapy.

Keywords

Antioxidant, apoptosis, cancer, honey, oxidative deoxyribonucleic acid (DNA) damage, reactive oxygen species

References

• T. Eteraf-Oskouei, M. Najafi, Uses of natural honey in cancer: An updated review, Advanced Pharmaceutical Bulletin 12 (2) (2022) 23 pages.
• World Health Organization, https://www.who.int/news-room/fact-sheets/detail/breast-cancer, Accessed: 27 May 2022.
• A. Wellstein, General principles in the pharmacotherapy of cancer, Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition, McGraw-Hill Education, New York, 2015, Ch. 65.
• A. Rezano, F. Ridhayanti, A. R. Rangkuti, T. Gunawan, G. N. A. Winarno, I. Wijaya, Cytotoxicity of simvastatin in human breast cancer MCF-7 and MDA-MB-231 cell lines, Asian Pacific Journal of Cancer Prevention 22 (2021) 33–42.
• K. N. Stevens, C. M. Vachon, F. J. Couch, Genetic susceptibility to triple-negative breast cancer, Cancer Research 73 (7) (2013) 2025–2030.
• A. Kabała-Dzik, A. Rzepecka-Stojko, R. Kubina, M. Iriti, R. D. Wojtyczka, E. Buszman, J. Stojko, Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7-A comparative study, Cellular and Molecular Biology 64 (8) (2018) 10 pages.
• B. Westley, H. Rochefort, Estradiol induced proteins in the MCF7 human breast cancer cell line, Biochemical and Biophysical Research Communications 90 (2) (1979) 410–416.
• B. S. Katzenellenbogen, K. L. Kendra, M. J. Norman, Y. Berthois, Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens, Cancer Research 47 (1987) 4355–4360.
• D. L. Holliday, V. Speirs, Choosing the right cell line for breast cancer research, Breast Cancer Research 13 (2011) Article Number 215 7 pages.
• A. R. M. R. Amin, O. Kucuk, F. R. Khuri, D. M. Shin, Perspectives for cancer prevention with natural compounds, Journal of Clinical Oncology 27 (16) (2009) 14 pages.
• W. Park, A. R. M. Ruhul Amin, Z. G. Chen, D. M. Shin, New perspectives of curcumin in cancer prevention, Cancer Prevention Research 6 (5) (2013) 20 pages.
• A. Haque, D. Brazeau, A. R. Amin, Perspectives on natural compounds in chemoprevention and treatment of cancer: An update with new promising compounds, European Journal of Cancer 149 (2021) 165–183.
• M. K. Shanmugam, J. H. Lee, E. Z. P. Chai, M. M. Kanchi, S. Kar, F. Arfuso, A. Dharmarajan, A. P. Kumar, P. S. Ramar, C. Y. Looi, M. R. Mustafa, V. Tergaonkar, A. Bishayee, K. S. Ahn, G. Sethi, Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds, Seminars in Cancer Biology 40-41 (2016) 35–47.
• S. Ahmed, S. A. Sulaiman, A. A. Baig, M. Ibrahim, S. Liaqat, S. Fatima, S. Jabeen, N. Shamim, N. H. Othman, Honey as a potential natural antioxidant medicine: An insight into its molecular mechanisms of action, Oxidative Medicine and Cellular Longevity 2018 (2018) Article ID 8367846 19 pages.
• R. J. Masad, S. M. Haneefa, Y. A. Mohamed, A. Al-Sbiei, G. Bashir, M. J. Fernandez-Cabezudo, B. K. al-Ramadi, The immunomodulatory effects of honey and associated flavonoids in cancer, Nutrients 13 (4) (2021) 15 pages.
• F. C. Biluca, B. da Silva, T. Caon, E. T. B. Mohr, G. N. Vieira, L. V. Gonzaga, L. Vitali, G. Micke, R. Fett, E. M. Dalmarco, A. C. O Costa, Investigation of phenolic compounds, antioxidant and anti-inflammatory activities in stingless bee honey (Meliponinae), Food Research International 129 (2020) 108756 9 pages.
• H. R. El-Seedi, N. Eid, A. A. A. El-Wahed, M. E. Rateb, H. S. Afifi, A. F. Algethami, C. Zhao, Y. Al Naggar, S. M. Alsharif, H. E. Tahir, B. Xu, K. Wang, S. A. M. Khalifa, Honey bee products: Preclinical and clinical studies of their anti-inflammatory and immunomodulatory properties, Frontiers in Nutrition 8 (2022) 19 pages.
• N. Ecem Bayram, M. O. Yüzer, S. Bayram, Melissopalynology analysis, physicochemical properties, multi-element content and antimicrobial activity of honey samples collected from Bayburt, Turkey, Uludağ Bee Journal 19 (2) (2019) 16 pages.
• S. Mežnarić, I. B. Karaconji, G. Crnkovic, A. Lesar, T. Pavlesic, D. Vuckovic, I. Gobin, Combined inhibitory effect of fir (Abies alba Mill.) honeydew honey and probiotic bacteria lactiplantibacillus plantarum on the growth of salmonella enterica serotype typhimurium, Antibiotics 11 (2) (2022) 13 pages.
• N. Akgün, Ö. F. Çelik, L. Kelebekli, Physicochemical properties, total phenolic content, and antioxidant activity of chestnut, rhododendron, acacia and multifloral honey, Journal of Food Measurement and Characterization 15 (4) (2021) 8 pages.
• D. S. Pena Júnior, C. A, Almeida, M. C. F. Santos, P. H. V. Fonseca, E. V. Menezes, A. F. de M. Junior, M. M. Brandao, D. A. de Oliveira, L. F. de Souza, J. C. Silva, V. de A. Royo, Antioxidant activities of some monofloral honey types produced across Minas Gerais (Brazil), PLoS One 17 (1) (2022) 12 pages.
• S. Samarghandian, J. T. Afshari, S. Davoodi, Honey induces apoptosis in renal cell carcinoma, Pharmacogn Mag 7 (25) (2011) 8 pages.
• B. Kaya, A. Yıldırım, Determination of the antioxidant, antimicrobial and anticancer properties of the honey phenolic extract of five different regions of Bingöl province, Journal of Food Science and Technology 58 (6) (2021) 2420–2430.
• Y. He, Y. Shi, Y. Yang, H. Huang, Y. Feng, Y. Wang, L. Zhan, B. Wei, Chrysin induces autophagy through the inactivation of the ROS-mediated Akt/mTOR signaling pathway in endometrial cancer, International Journal of Molecular Medicine 48 (3) (2021) 13 pages.
• D. Bose, A. Chaudhary, M. Padmavati, J. Chatterjee, R. Banerjee, In vitro evaluation of anti-proliferative activity of protein from Litchi chinensis honey against human cervical cancer cell line (HeLa), Journal of Herbal Medicine 31 (2022) 100518 8 pages.
• E. M. Halawani, Potential effects of Saudi Shaoka (Fagonia bruguieri) honey against multi-drug-resistant bacteria and cancer cells in comparison to Manuka honey, Saudi Journal of Biological Sciences 28 (12) (2021) 11 pages.
• A. N. Fauzi, N. S. Yaacob, Cell cycle and apoptosis pathway modulation by Tualang honey in ER-dependent and -independent breast cancer cell lines, Journal of Apicultural Research 55 (5) (2016) 11 pages.
• M. Sakač, P. Jovanov, A. Marić, D. Četojević-Simin, A. Novaković, D. Plavšić, D. Škrobot, R. Kovač, Antioxidative, antibacterial and anti-proliferative properties of honey types from the western Balkans, Antioxidants 11 (6) (2022) 1120 14 pages.
• M. A. Al-Kafaween, M. Alwahsh, A. B. Mohd Hilmi, D. H. Abulebdah, Physicochemical characteristics and bioactive compounds of different types of honey and their biological and therapeutic properties: A comprehensive review, Antibiotics 12 (2) (2023) 337 34 pages.
• L. D. O. Sant'Ana, A. B. Buarque Ferreira, M. C. A. Lorenzon, R. L. L. Berbara, R. N. Castro, Correlation of total phenolic and flavonoid contents of Brazilian honey with colour and antioxidant capacity, International Journal of Food Properties 17 (1) (2014) 30 pages.
• Statista (2022), https://www.statista.com/statistics/812172/global-top-producers-of-honey/, Accessed 17 Oct 2022.
• E. Demirhan, Siirt’ten şifa kaynağı: Pervari balı, Türk Tarım Orman Dergisi 270 (2022) 82–85.
• V. L. Singleton, J. A. Rossi, Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents, American Journal of Enology and Viticulture 16 (3) (1965) 144–158.
• Z. Cheng, J. Moore, L. Yu, High-throughput relative DPPH radical scavenging capacity assay, Journal of Agricultural and Food Chemistry 54 (20) (2006) 7429–7436.
• T. Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, Journal of Immunological Methods 65 (1–2) (1983) 55–63.
• S. Kiokias, V. Oreopoulou, A review of the health protective effects of phenolic acids against a range of severe pathologic conditions (Including coronavirus-based infections), Molecules 26 (17) (2021) 5405 18 pages.
• M. Z. Mumtaz, F. Kausar, M. Hassan, S. Javaid, A. Malik, Anticancer activities of phenolic compounds from Moringa oleifera leaves: in vitro and in silico mechanistic study, Beni-Suef University Journal of Basic and Applied Sciences 10 (1) (2021) 11 pages.
• J. Duan, H. Guo, Y. Fang, G. Zhou, The mechanisms of wine phenolic compounds for preclinical anticancer therapeutics, Food & Nutrition Research 65 (2021) 15 pages.
• I. C. da S. Haas, D. J. Marmitt, I. M. T. Fedrigo, M. I. Goettert, M. T. Bordignon-Luiz, Evaluation of anti-proliferative and anti-inflammatory effects of non-pomace sediment of red grape juices (Vitis labrusca L.) in healthy and cancer cells after in vitro gastrointestinal simulation, PharmaNutrition 13 (2020) 100204 31 pages.
• Z. Can, O. Yildiz, H. Sahin, E. Akyuz Turumtay, S. Silici, S. Kolayli, An investigation of Turkish honeys: Their physico-chemical properties, antioxidant capacities and phenolic profiles, Food Chemistry 180 (2015) 133–141.
• M. F. Seyhan, E. Yılmaz, Ö. Timirci Kahraman, N. Saygılı, H. İ. Kısakesen, A. P. Eronat, A. B. Ceviz, S. B. Gazioğlu, H. Yılmaz Aydoğan, O. Öztürk, Anatolian honey is not only sweet but can also protect from breast cancer: Elixir for women from Artemis to present, IUBMB Life 69 (9) (2017) 12 pages.
• H. Sipahi, G. Aydogan, S. Helvacioglu, M. Charehsaz, E. Guzelmeric, A. Aydin, Antioxidant, anti-inflammatory and antimutagenic activities of various kinds of Turkish honey, Fabad Journal of Pharmaceutical Sciences 42 (1) (2017) 7–13.
• M. Ozcan, D. Aydemir, M. Bacanlı, H. G. Anlar, N. N. Ulusu, Y. Aksoy, Protective effects of antioxidant chlorophyllin in chemically induced breast cancer model in vivo, Biological Trace Element Research 199 (12) (2021) 4475–4488.
• J. Bertoncelj, U. Doberšek, M. Jamnik, T. Golob, Evaluation of the phenolic content, antioxidant activity and colour of Slovenian honey, Food Chemistry 105 (2) (2007) 822–828.
• A. Alves, A. Ramos, M. M. Gonçalves, M. Bernardo, B. Mendes, Antioxidant activity, quality parameters and mineral content of Portuguese monofloral honey, Journal of Food Composition and Analysis 30 (2) (2013) 130–138.
• M. Taş-Küçükaydın, G. Tel Çayan, F. Çayan, S. Küçükaydın, B. H. Çiftçi, Ö. Ceylan, M. E. Duru, Chemometric classification of chestnut honey from different regions in Turkey based on their phenolic compositions and biological activities, Food Chemistry 415 (2023) 135727 10 pages.
• A. N. Fauzi, M. N. Norazmi, N. S. Yaacob, Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines, Food and Chemical Toxicology 49 (4) (2011) 871–878.
• J. S. Câmara, B. R. Albuquerque, J. Aguiar, R. C. G. Corrêa, J. L. Gonçalves, D. Granato, J. A. M. Pereira, L. Barros, I. C. F. R. Ferreira, Food bioactive compounds and emerging techniques for their extraction: Polyphenols as a case study, Foods 10 (1) (2021) 34 pages.
• M. Samtiya, R. E. Aluko, T. Dhewa, J. M. Moreno-Rojas, Potential health benefits of plant food-derived bioactive components: An overview, Foods 10 (4) (2021) 25 pages.
• E. Kurtdede, M. E. Alçiğir, A. M. Alperen, B. Baran, O. K. Karaca, E. Gülendağ, Evaluation of the combined effects of Turkish mad honey and 5-Fluorouracil in colon cancer model in rats, Veterinary Journal of Ankara University 70 (4) (2023) 427–435.
• T. Ozdal, G. Sari-Kaplan, E. Mutlu-Altundag, D. Boyacioglu, E. Capanoglu, Evaluation of Turkish propolis for its chemical composition, antioxidant capacity, anti-proliferative effect on several human breast cancer cell lines and proliferative effect on fibroblasts and mouse mesenchymal stem cell line, Journal of Apicultural Research 57 (5) (2018) 12 pages.
• F. L. Sarmiento-Salinas, A. Perez-Gonzalez, A. Acosta-Casique, A. Ix-Ballote, A. Diaz, S. Treviño, N. H. Rosas-Murrieta, L. Millán-Perez-Peña, P. Maycotte, Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression, Life Sciences 284 (2021) 119942 13 pages.
• M. L. Balestrieri, A. Dicitore, R. Benevento, M. di Maio, A. Santoriello, S. Canonico, A. Giordano, P. Stiuso, Interplay between membrane lipid peroxidation, transglutaminase activity, and Cyclooxygenase 2 expression in the tissue adjoining to breast cancer, Journal of Cellular Physiology 227 (2012) 1577–1582.
• X. Zhang, Y. Xiao, Q. Huang, The cellular uptake of Cordyceps sinensis exopolysaccharide selenium nanoparticles and their induced apoptosis of HepG2 cells via mitochondria- and death receptor-mediated pathways, International Journal of Biological Macromolecules 247 (2023) 125747 14 pages.
• X. Y. Tang, S. J. Yu, X. M. Guo, H. Li, M. S. Chen, T. Zhang, C. Y. Lei, Z. G. Zhao, H. C. Meng, Betacyanins functionalized selenium nanoparticles inhibit HepG2 cells growth via mitochondria-mediated pathway, Journal of Functional Foods 78 (2021) 104359 11 pages.
• M. Hornsveld, T. B. Dansen, The hallmarks of cancer from a redox perspective, Antioxidants and Redox Signaling 25 (6) (2016) 26 pages.
• G. Y. Liou, P. Storz, Reactive oxygen species in cancer, Free Radical Research 44 (5) (2010) 479–496.
• A. Alamri, A review of the anticancer properties of bee products and their molecular mechanisms: An overview on lung cancer, Tropical Journal of Pharmaceutical Research 20 (8) (2021) 1765–1774.
• S. K. Jaganathan, M. Mandal, Involvement of non-protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induced apoptosis, Invest New Drugs 28 (5) (2010) 624–633.
• S. Afrin, T. Y Forbes-Hernandez, M. Gasparrini, S. Bompadre, J. L. Quiles, G. Sanna, N. Spano, F. Giampieri, M. Battino, Strawberry-tree honey induces growth inhibition of human colon cancer cells and increases ros generation: A comparison with manuka honey, International Journal of Molecular Sciences 18 (3) (2017) 19 pages.
• D. Cianciosi, T. Y. Forbes-Hernández, S. Afrin, M. Gasparrini, J. L Quiles, E. Gil, S. Bompadre, J. Simal-Gandara, M. Battino, F. Giampieri, The influence of in vitro gastrointestinal digestion on the anticancer activity of manuka honey, Antioxidants 9 (1) (2020) 20 pages.
• X. Zhao, A. Abulikemu, S. Lv, Y. Qi, J. Duan, J. Zhang, R. Chen, C. Guo, Y. Li, Z. Sun, Oxidative stress- and mitochondrial dysfunction-mediated cytotoxicity by silica nanoparticle in lung epithelial cells from metabolomic perspective, Chemosphere 275 (2021) 129969 14 pages.
• A. L. Becerrilsánchez, B. Quintero‐Salazar, O. Dublán‐García, H. B. Escalona‐Buendía, Phenolic compounds in honey and their relationship with antioxidant activity, botanical origin, and color, Antioxidants 10 (11) (2021) 23 pages.
• J. Musarrat, J. Arezina-Wilson, A. A. Wani, Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast carcinogenesis, European Journal of Cancer Part 32A (7) (1996) 1209–1214.
• J. S. Helm, R. A. Rudel, Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast, Archives of Toxicology 94 (5) (2020) 39 pages.
• J. Wunder, D. Pemp, A. Cecil, M. Mahdiani, R. Hauptstein, K. Schmalbach, L. N. Geppert, K. Ickstadt, H. L. Esch, T. Dandekar, L. Lehmann, Influence of breast cancer risk factors on proliferation and DNA damage in human breast glandular tissues: Role of intracellular estrogen levels, oxidative stress and estrogen biotransformation, Archives of Toxicology 96 (2) (2022) 673–687.