Investigating the anticancer potential of boric acid against human gastric adenocarcinoma cells
Yıl 2025,
Cilt: 10 Sayı: 4, 140 - 149, 31.12.2025
Aslıhan Kartal
,
Sezen Atasoy
Öz
Gastric cancer is a major contributor to cancer-related mortality worldwide, and the search for effective, targeted, and biocompatible therapeutic agents remains ongoing. Boric acid, a biologically active and low toxicity boron compound, has recently gained attention for its potential anticancer properties. This study aimed to investigate cytotoxic and proapoptotic effects of boric acid on human gastric adenocarcinoma cells (AGS) in vitro. The cell viability was assessed using a cytotoxicity assay following 24 h boric acid treatment, the IC50 value for AGS cells can be confidently stated as <78.12 μM, while HEK293T nonmalignant cells showed minimal sensitivity, indicating selective cytotoxicity toward cancer cells. To further evaluate the mechanism of cell death, Annexin V-FITC and 7-AAD staining was performed via fluorescence microscopy and flow cytometry. Microscopy analysis revealed a substantial rise in Annexin V-FITC and 7-AAD-positive cells in the treated group compared to controls (p<0,0001). Flow cytometry corroborated these results, showing 7.7% early apoptosis and 16.3% late apoptosis in boric acid-treated cells, versus minimal apoptotic activity in controls, with statistically significant increases in early and late apoptotic populations (p<0,01 and p<0,001, respectively). These results suggest that boric acid induces programmed cell death in AGS gastric adenocarcinoma cells, highlighting its promise as a potential therapeutic option in gastric cancer therapy. The data presented here provides preliminary evidence for the anticancer potential of boric acid and supports ongoing investigations into the therapeutic potential of boron compounds.
Etik Beyan
We hereby declare that all stages of the study were conducted in accordance with research and publication ethics, and that we have complied with ethical guidelines and the principles of scientific citation.
Destekleyen Kurum
Scientific and Technological Research Council of Turkey (TUBITAK)
Proje Numarası
1919B012407903
Teşekkür
This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 1919B012407903. The authors thank to TUBITAK for their supports. The authors would also like to express their gratitude to the Pharmaceutical Application and Research Center and Department of Pharmacogonosy at Bezmialem Vakif University for their support with laboratory access and technical resources.
Kaynakça
-
Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C., & Lordick, F. (2020). Gastric cancer. Lancet, 396(10251), 635-648. https://doi.org/10.1016/S0140-6736(20)31288-5
-
Karimi, P., Islami, F., Anandasabapathy, S., Freedman, N. D., & Kamangar, F. (2014). Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prevention, 23(5), 700-13. https://doi.org/10.1158/1055-9965.EPI-13-1057
-
López, M. J., Carbajal, J., Alfaro, A. L., Saravia, L. G., Zanabria, D., Araujo, J. M., … & Fajardo, W. (2023). Characteristics of gastric cancer around the world. Critical Reviews in Oncology/Hematology, 181, 103841. https://doi.org/10.1016/j.critrevonc.2022.103841
-
Sundar, R., Nakayama, I., Markar, S. R., Shitara, K., van Laarhoven, H. W. M., Janjigian, Y. Y., & Smyth, E. C. (2025). Gastric cancer. Lancet, 405(10494), 2087-2102. https://doi.org/10.1016/S0140-6736(25)00052-2
-
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal of Clinicians, 74(3), 229-263. https://doi.org/10.3322/caac.21834
-
Guner, A. (2017). Recent trends of gastric cancer treatment in Turkey. Translational Gastroenterology and Hepatology, 2, 31. https://doi.org/10.21037/tgh.2017.04.01
-
Lordick, F., Carneiro, F., Cascinu, S., Fleitas, T., Haustermans, K., Piessen, G., … & Smyth, E. C. (2022). Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Annals of Oncology, 33(10), 1005-1020. https://doi.org/10.1016/j.annonc.2022.07.004
-
Ajani, J. A., D’Amico, T. A., Bentrem, D. J., Chao, J., Cooke, D., Corvera, C., … & Pluchino, L. A. (2022). Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 20(2), 167-192. https://doi.org/10.6004/jnccn.2022.0008
-
Eom, S. S., Ryu, K. W., Han, H. S., & Kong, S. H. (2025). A Comprehensive and comparative review of global gastric cancer treatment guidelines: 2024 update. J Gastric Cancer, 25(1), 153-176. https://doi.org/10.5230/jgc.2025.25.e10
-
Wu, M., Yuan, S., Liu, K., Wang, C., & Wen, F. (2024). Gastric cancer signaling pathways and therapeutic applications. Technology in Cancer Research & Treatment, 23. https://doi.org/10.1177/15330338241271935
-
Yasuda, T., & Wang, Y. A. (2024). Gastric cancer immunosuppressive microenvironment heterogeneity: Implications for therapy development. Trends Cancer, 10(7), 627-642. https://doi.org/10.1016/j.trecan.2024.03.008
-
Chunarkar-Patil, P., Kaleem, M., Mishra, R., Ray, S., Ahmad, A., Verma, D., … & Kumar, S. (2024). Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomedicines, 12(1), 201. https://doi.org/10.3390/biomedicines12010201
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Kulkarni, S., Bhandary, D., Singh, Y., Monga, V., & Thareja, S. (2023). Boron in cancer therapeutics: An overview. Pharmacol Ther, 251, 108548. https://doi.org/10.1016/j.pharmthera.2023.108548
-
Darcansoy İseri, Ö., & Dikkatli, Ö. I. (2023). Boron and beyond: Where do we stand in cancer treatment? Journal of Boron, 8(4), 158-188. https://doi.org/10.30728/boron.1292418
-
Ou, M., Wang, X., Yu, L., Liu, C., Tao, W., Ji, X., & Mei, L. (2021). The emergence and evolution of borophene. Advanced Science, 8(12), 2001801. https://doi.org/10.1002/advs.202001801
-
Çöl, B., Dibek, E., Babayeva, A., Sezer Kürkçü, M., & Akgüç Çöl, N. (2020). Bor içeren bazı biyoaktif bileşikler. Journal of Boron, 5(1), 29-39. https://doi.org/10.30728/boron.604069
-
Penland, J. G. (1994). Dietary boron, brain function, and cognitive performance. Environmental Health Perspectives, 102(suppl 7), 65-72. https://doi.org/10.1289/ehp.94102s765
-
Biţă, A., Scorei, I. R., Bălşeanu, T. A., Ciocîlteu, M. V., Bejenaru, C., Radu, A., … & Benner, S. A. (2022). New insights into boron essentiality in humans and animals. International Journal of Molecular Sciences, 23(16), https://doi.org/10.3390/ijms23169147
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Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological Trace Element Research, 186, 31-51. https://doi.org/10.1007/s12011-018-1284-3
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Nielsen, F. H., & Eckhert, C. D. (2020). Boron. Advances in Nutrition, 11(2), 461-462. https://doi.org/10.1093/advances/nmz110
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Bitmez, B., & Balbal, B. (2024). Alzheimer ve Parkinson hastalıklarında bor içeren bileşiklerin nörokoruyucu etkisi. Journal of Boron, 9(1), 42-51. https://doi.org/10.30728/boron.1408368
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Deliboran, A. (2020). Neden bor? borun çevre ile insan, hayvan ve bitki sağliği açisindan önemi. Bahçe, 49(2), 127-141.
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Karabulut Uzunçakmak, S. (2023). The effect of boric acid, calcium fructoborate and potassium boron citrate on bone health in rats. Journal of Boron, 8(1), 9-15. https://doi.org/10.30728/boron.1142574
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Scorei, R. I., & Popa, R., Jr. (2010). Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti-cancer Agents in Medicinal Chemistry, 10(4), 346-51. https://doi.org/10.2174/187152010791162289
-
Liu, J., Zhao, R., Jiang, X., Li, Z., & Zhang, B. (2021). Progress on the application of bortezomib and bortezomib-based nanoformulations. Biomolecules, 12(1), https://doi.org/10.3390/biom12010051
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Borik asidin antikanser potansiyelinin insan gastrik adenokarsinom hücrelerinde araştırılması
Yıl 2025,
Cilt: 10 Sayı: 4, 140 - 149, 31.12.2025
Aslıhan Kartal
,
Sezen Atasoy
Öz
Mide kanseri, dünya genelinde kanserle ilişkili ölümlerin başlıca nedenlerinden biri olup, etkili, hedeflli ve biyouyumlu tedavi edici ajanlara yönelik araştırmaları devam etmektedir. Biyolojik olarak aktif ve düşük toksisiteye sahip bir bor bileşiği olan borik asit, son zamanlarda potansiyel antikanser özellikleri nedeniyle dikkat çekmektedir. Bu çalışma, borik asidin AGS insan mide adenokarsinom hücreleri üzerindeki sitotoksik ve pro-apoptotik etkilerini in vitro olarak araştırmayı amaçlamıştır. Borik asit ile farklı konsantrasyonlarda 24 saatlik muamele sonrası sitotoksisite testi ile hücre canlılığı değerlendirilmiştir. Hücre canlılığında doza bağımlı bir azalma gözlemlenmiştir. Hücre ölüm mekanizmasının daha ayrıntılı incelenmesi amacıyla Annexin V-FITC ve 7-AAD boyamaları floresan mikroskobu ve akım sitometrisi ile gerçekleştirilmiştir. Floresan görüntülemede muamele edilen grup Annexin V ve 7-AAD pozitif hücrelerde anlamlı bir artış göstermiştir ve bu durum apoptoza işaret etmektedir. Akım sitometrisi analizi de bu bulguları doğrulamış, borik asit uygulaması sonrası canlı hücrelerden erken ve geç apoptotik hücre popülasyonlarına belirgin bir geçiş olduğunu ortaya koymuştur. Bu sonuçlar, borik asidin AGS mide adenokarsinom hücrelerinde programlanmış hücre ölümünü indüklediğini göstermekte olup, mide kanseri tedavisinde potansiyel bir terapötik ajan olabileceğini düşündürmektedir. Bu çalışma, borik asidin antikanser potansiyeline dair öncü bulgular sunmakta ve bor bileşiklerinin terapötik etkilerine yönelik yürütülen araştırmaları desteklemektedir.
Proje Numarası
1919B012407903
Kaynakça
-
Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C., & Lordick, F. (2020). Gastric cancer. Lancet, 396(10251), 635-648. https://doi.org/10.1016/S0140-6736(20)31288-5
-
Karimi, P., Islami, F., Anandasabapathy, S., Freedman, N. D., & Kamangar, F. (2014). Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prevention, 23(5), 700-13. https://doi.org/10.1158/1055-9965.EPI-13-1057
-
López, M. J., Carbajal, J., Alfaro, A. L., Saravia, L. G., Zanabria, D., Araujo, J. M., … & Fajardo, W. (2023). Characteristics of gastric cancer around the world. Critical Reviews in Oncology/Hematology, 181, 103841. https://doi.org/10.1016/j.critrevonc.2022.103841
-
Sundar, R., Nakayama, I., Markar, S. R., Shitara, K., van Laarhoven, H. W. M., Janjigian, Y. Y., & Smyth, E. C. (2025). Gastric cancer. Lancet, 405(10494), 2087-2102. https://doi.org/10.1016/S0140-6736(25)00052-2
-
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal of Clinicians, 74(3), 229-263. https://doi.org/10.3322/caac.21834
-
Guner, A. (2017). Recent trends of gastric cancer treatment in Turkey. Translational Gastroenterology and Hepatology, 2, 31. https://doi.org/10.21037/tgh.2017.04.01
-
Lordick, F., Carneiro, F., Cascinu, S., Fleitas, T., Haustermans, K., Piessen, G., … & Smyth, E. C. (2022). Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Annals of Oncology, 33(10), 1005-1020. https://doi.org/10.1016/j.annonc.2022.07.004
-
Ajani, J. A., D’Amico, T. A., Bentrem, D. J., Chao, J., Cooke, D., Corvera, C., … & Pluchino, L. A. (2022). Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 20(2), 167-192. https://doi.org/10.6004/jnccn.2022.0008
-
Eom, S. S., Ryu, K. W., Han, H. S., & Kong, S. H. (2025). A Comprehensive and comparative review of global gastric cancer treatment guidelines: 2024 update. J Gastric Cancer, 25(1), 153-176. https://doi.org/10.5230/jgc.2025.25.e10
-
Wu, M., Yuan, S., Liu, K., Wang, C., & Wen, F. (2024). Gastric cancer signaling pathways and therapeutic applications. Technology in Cancer Research & Treatment, 23. https://doi.org/10.1177/15330338241271935
-
Yasuda, T., & Wang, Y. A. (2024). Gastric cancer immunosuppressive microenvironment heterogeneity: Implications for therapy development. Trends Cancer, 10(7), 627-642. https://doi.org/10.1016/j.trecan.2024.03.008
-
Chunarkar-Patil, P., Kaleem, M., Mishra, R., Ray, S., Ahmad, A., Verma, D., … & Kumar, S. (2024). Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomedicines, 12(1), 201. https://doi.org/10.3390/biomedicines12010201
-
Kulkarni, S., Bhandary, D., Singh, Y., Monga, V., & Thareja, S. (2023). Boron in cancer therapeutics: An overview. Pharmacol Ther, 251, 108548. https://doi.org/10.1016/j.pharmthera.2023.108548
-
Darcansoy İseri, Ö., & Dikkatli, Ö. I. (2023). Boron and beyond: Where do we stand in cancer treatment? Journal of Boron, 8(4), 158-188. https://doi.org/10.30728/boron.1292418
-
Ou, M., Wang, X., Yu, L., Liu, C., Tao, W., Ji, X., & Mei, L. (2021). The emergence and evolution of borophene. Advanced Science, 8(12), 2001801. https://doi.org/10.1002/advs.202001801
-
Çöl, B., Dibek, E., Babayeva, A., Sezer Kürkçü, M., & Akgüç Çöl, N. (2020). Bor içeren bazı biyoaktif bileşikler. Journal of Boron, 5(1), 29-39. https://doi.org/10.30728/boron.604069
-
Penland, J. G. (1994). Dietary boron, brain function, and cognitive performance. Environmental Health Perspectives, 102(suppl 7), 65-72. https://doi.org/10.1289/ehp.94102s765
-
Biţă, A., Scorei, I. R., Bălşeanu, T. A., Ciocîlteu, M. V., Bejenaru, C., Radu, A., … & Benner, S. A. (2022). New insights into boron essentiality in humans and animals. International Journal of Molecular Sciences, 23(16), https://doi.org/10.3390/ijms23169147
-
Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological Trace Element Research, 186, 31-51. https://doi.org/10.1007/s12011-018-1284-3
-
Nielsen, F. H., & Eckhert, C. D. (2020). Boron. Advances in Nutrition, 11(2), 461-462. https://doi.org/10.1093/advances/nmz110
-
Bitmez, B., & Balbal, B. (2024). Alzheimer ve Parkinson hastalıklarında bor içeren bileşiklerin nörokoruyucu etkisi. Journal of Boron, 9(1), 42-51. https://doi.org/10.30728/boron.1408368
-
Deliboran, A. (2020). Neden bor? borun çevre ile insan, hayvan ve bitki sağliği açisindan önemi. Bahçe, 49(2), 127-141.
-
Karabulut Uzunçakmak, S. (2023). The effect of boric acid, calcium fructoborate and potassium boron citrate on bone health in rats. Journal of Boron, 8(1), 9-15. https://doi.org/10.30728/boron.1142574
-
Scorei, R. I., & Popa, R., Jr. (2010). Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti-cancer Agents in Medicinal Chemistry, 10(4), 346-51. https://doi.org/10.2174/187152010791162289
-
Liu, J., Zhao, R., Jiang, X., Li, Z., & Zhang, B. (2021). Progress on the application of bortezomib and bortezomib-based nanoformulations. Biomolecules, 12(1), https://doi.org/10.3390/biom12010051
-
Trivillin, V. A., Serrano, A., Garabalino, M. A., Colombo, L. L., Pozzi, E. C., Hughes, A. M., … & Schwint, A. E. (2019). Translational boron neutron capture therapy (BNCT) studies for the treatment of tumors in lung. International Journal of Radiation Biology, 95(5), 646-654. https://doi.org/10.1080/09553002.2019.1564080
-
Yakıncı, Z. D., & Kök, M. (2016). Borun sağlık alanında kullanımı. İnönü Üniversitesi Sağlık Hizmetleri Meslek Yüksek Okulu Dergisi, 4(1), 36-44.
-
Gölge, U. H., Kaymaz, B., Arpaci, R., Kömürcü, E., Göksel, F., Güven, M., … & Cevizci, S. (2015). Effects of boric acid on fracture healing: An experimental study. Biological Trace Element Research, 167(2), 264-271. https://doi.org/10.1007/s12011-015-0326-3
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