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Does Boric Acid Inhibit Cell Proliferation on MCF-7 and MDA-MB-231 Cells in Monolayer and Spheroid Cultures by Using Apoptosis Pathways?

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Abstract

Most breast cancers originate in the lobules or ducts of the breast. Breast cancer as the second main cause of death among women in the world is the most common kind of cancer in women. Studies have been conducted to find the optimal treatment for breast cancer. Moreover, the therapeutic effects of different drugs and substances on this disease have been intensively researched. Boric acid accounts for 96% of the boron content in body fluids, and its derivatives are absorbed by the human body. It is assumed to be represented as (B(OH)2). Experimental studies have shown a reduction of cell proliferation and stimulation of apoptosis in some melanoma, prostate, and colon cancer cell lines through boric acid. The aim of this study was to investigate if boric acid could be used for treating breast cancer. The impacts of boric acid on the human breast carcinoma cell lines MCF-7 and MDA-MB-231 were studied with TUNEL, BrdU, caspase-3, and endo-G immunohistochemical studies in 3D and 2D culture systems. Furthermore, we conducted a qRT-PCR study to show changes in the expression of some genes involved in apoptosis. Suppression of cell proliferation through boric acid–inducing apoptosis was observed both in 3D and 2D culture conditions. These results are compatible with the gene expression results. The ENDOG, CASP3, CASP8, and CASP9 gene expression significantly changed at all time intervals in MCF-7 and MD-MB-231 cell lines boric acid can potentially treat breast cancer as an anti-cancer agent candidate.

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Data Availability

Our study is a cell culture study. Cell lines used in the study DSMZ-German Collection of Microorganisms and Cell Cultures GmbH was provided. In accordance with German law (Biostoffverordnung), the DSMZ has carried out biological risk assessments for every cell line in the collection. Due to the nature of the research, due to [ethical/legal/commercial] supporting data is not available.

References

  1. Terlikowska K, Witkowska A, Terlikowski S (2014) Curcumin in chemoprevention of breast cancer. Postepy Hig Med Dosw 68:571–578. https://doi.org/10.5604/17322693.1102294

    Article  Google Scholar 

  2. Kahraman E, Göker E (2023) Boric Acid Treatment Strengthens the Cytotoxic Effect of Sorafenib on Triple Negative Breast Cancer Cell Lines. Celal Bayar University J Sci 19(2):137–141

    CAS  Google Scholar 

  3. Burstein HJ, Curigliano G, Thurlimann B, Weber WP, Poortmans P, Regan MM et al (2021) Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol 32(10):1216–1235. https://doi.org/10.1016/j.annonc.2021.06.023

    Article  CAS  PubMed  Google Scholar 

  4. Murphy N, McCarthy E, Dwyer R, Farras P (2021) Boron clusters as breast cancer therapeutics. J Inorg Biochem 218:111412. https://doi.org/10.1016/j.jinorgbio.2021.111412

    Article  CAS  PubMed  Google Scholar 

  5. Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D et al (2006) Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep 23(3):394–411. https://doi.org/10.1039/b515312n

    Article  CAS  PubMed  Google Scholar 

  6. Cragg GM, Newman DJ (2009) Nature: a vital source of leads for anticancer drug development. Phytochem Rev 8(2):313–331. https://doi.org/10.1007/s11101-009-9123-y

    Article  CAS  Google Scholar 

  7. Akram M, Iqbal M, Daniyal M, Khan AU (2017) Awareness and current knowledge of breast cancer. Biol Res 50(1):33. https://doi.org/10.1186/s40659-017-0140-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Arpino G, Bardou VJ, Clark GM, Elledge RM (2004) Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 6(3):R149–R156. https://doi.org/10.1186/bcr767

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sezekler I, Ersoz M, Turan MA, Coskun ZM (2020) Investigation of the biochemical and apoptotic changes in breast cancer cells treated with leaf extract from tea (Camellia sinensis L.) grown with added boric acid. Pak J Pharm Sci 33(5):1927–1932

    CAS  PubMed  Google Scholar 

  10. Scaria B, Sood S, Raad C, Khanafer J, Jayachandiran R, Pupulin A et al (2020) Natural Health Products (NHP's) and natural compounds as therapeutic agents for the treatment of cancer; mechanisms of anti-cancer activity of natural compounds and overall trends. Int J Mol Sci 21(22). https://doi.org/10.3390/ijms21228480

  11. Sevimli M, Bayram D, Ozgocmen M, Armagan I, Sevimli TS (2022) Boric acid suppresses cell proliferation by TNF signaling pathway mediated apoptosis in SW-480 human colon cancer line. J Trace Elem Med Biol 71. https://doi.org/10.1016/j.jtemb.2022.126958

  12. Wang Y, Zhao Y, Chen X (2008) Experimental study on the estrogen-like effect of boric Acid. Biol Trace Elem Res 121(2):160–170. https://doi.org/10.1007/s12011-007-8041-3

    Article  CAS  PubMed  Google Scholar 

  13. Barranco WT, Hudak PF, Eckhert CD (2007) Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States). Cancer Causes Control 18(1):71–77. https://doi.org/10.1007/s10552-006-0077-8

    Article  PubMed  Google Scholar 

  14. Yilmaz S, Ustundag A, Ulker OC, Duydu Y (2016) Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines. Cell J 17(4):748–754

    PubMed  PubMed Central  Google Scholar 

  15. Mohammed EE, Turkel N, Yigit UM, Dalan AB, Sahin F (2023) Boron derivatives inhibit the proliferation of breast cancer cells and affect tumor-specific T cell activity in vitro by distinct mechanisms. Biol Trace Elem Res. https://doi.org/10.1007/s12011-023-03632-0

  16. Bradke TM, Hall C, Carper SW, Plopper GE (2008) Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and decreases viability. Cell Adh Migr 2(3):153–160. https://doi.org/10.4161/cam.2.3.6484

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cui Y, Winton MI, Zhang ZF, Rainey C, Marshall J, De Kernion JB et al (2004) Dietary boron intake and prostate cancer risk. Oncol Rep 11(4):887–892

    CAS  PubMed  Google Scholar 

  18. Korkmaz M, Uzgoren E, Bakirdere S, Aydin F, Ataman OY (2007) Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. Environ Toxicol 22(1):17–25. https://doi.org/10.1002/tox.20229

    Article  CAS  PubMed  Google Scholar 

  19. Mahabir S, Spitz MR, Barrera SL, Dong YQ, Eastham C, Forman MR (2008) Dietary boron and hormone replacement therapy as risk factors for lung cancer in women. Am J Epidemiol 167(9):1070–1080. https://doi.org/10.1093/aje/kwn021

    Article  CAS  PubMed  Google Scholar 

  20. Bayram D, Armagan I, Ozgocmen M, Senol N, Calapoglu M (2018) Determination of apoptotic effect of juglone on human bladder cancer TCC-SUP and RT-4 Cells: an in vitro study. J Environ Pathol Toxicol Oncol 37(2):173–181. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2018025226

    Article  PubMed  Google Scholar 

  21. Fedchenko N, Reifenrath J (2014) Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagn Pathol :9. https://doi.org/10.1186/s13000-014-0221-9

  22. Celik DA, Gurbuz N, Togay VA, Ozcelik N (2020) Ochratoxin A causes cell cycle arrest in G1 and G1/S phases through p53 in HK-2 cells. Toxicon 180:11–17. https://doi.org/10.1016/j.toxicon.2020.03.012

    Article  CAS  Google Scholar 

  23. Ozgocmen M, Bayram D, Yavuz Turel G, Togay VA, Sahin CN (2021) Secoisolariciresinol diglucoside induces caspase-3-mediated apoptosis in monolayer and spheroid cultures of human colon carcinoma cells. J Food Biochem 45(5):e13719. https://doi.org/10.1111/jfbc.13719

    Article  CAS  PubMed  Google Scholar 

  24. Ahmad N, Ammar A, Storr SJ, Green AR, Rakha E, Ellis IO et al (2018) IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunol Immunother 67(4):537–549. https://doi.org/10.1007/s00262-017-2106-8

    Article  CAS  PubMed  Google Scholar 

  25. Nielsen FH (2014) Update on human health effects of boron. J Trace Elem Med Biol 28(4):383–387. https://doi.org/10.1016/j.jtemb.2014.06.023

    Article  CAS  PubMed  Google Scholar 

  26. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G (2020) High concentrations of boric acid trigger concentration-dependent oxidative stress, apoptotic pathways and morphological alterations in DU-145 human prostate cancer cell line. Biol Trace Elem Res 193(2):400–409. https://doi.org/10.1007/s12011-019-01739-x

    Article  CAS  PubMed  Google Scholar 

  27. Simsek F, Inan S, Korkmaz M (2019) An in vitro study in which new boron derivatives maybe an option for breast cancer treatment. EJMO 3(1):22–27. https://doi.org/10.14744/ejmo.2018.0020

    Article  Google Scholar 

  28. Fırat F, Aladağ T (2022) Comparative Effects of Boric Acid and Resveratrol on MCF-7 Breast Cancer Cells Metastatic Behaviour. Int J Res-GRANTHAALAYAH 10(1):34–46. https://doi.org/10.29121/Granthaalayah.V10.İ1.2022.4460

    Article  Google Scholar 

  29. Eroz M (2021) Antioxidant and Anti-cancer Activity of Boric Acid in 8305C Anaplastic Thyroid Cancer Cells. Gümüşhane University J Health Sci 10(2):213–221. https://doi.org/10.37989/gumussagbil.834614

    Article  Google Scholar 

  30. Acerbo AS, Miller LM (2009) Assessment of the chemical changes induced in human melanoma cells by boric acid treatment using infrared imaging. Analyst 134(8):1669–1674. https://doi.org/10.1039/b823234b

    Article  CAS  PubMed  Google Scholar 

  31. Evan GI, Vousden KH (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411(6835):342–348. https://doi.org/10.1038/35077213

    Article  CAS  PubMed  Google Scholar 

  32. Bologna-Molina R, Mosqueda-Taylor A, Molina-Frechero N, Mori-Estevez AD, Sanchez-Acuna G (2013) Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumors. Med Oral Patol Oral 18(2):E174–E1E9

    Article  Google Scholar 

  33. Kyrylkova K, Kyryachenko S, Leid M, Kioussi C (2012) Detection of apoptosis by TUNEL assay. Methods Mol Biol 887:41–47. https://doi.org/10.1007/978-1-61779-860-3_5

    Article  CAS  PubMed  Google Scholar 

  34. Scorei RI, Popa R (2010) Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti-Cancer Agent Me 10(4):346–351

    Article  CAS  Google Scholar 

  35. Degterev A, Boyce M, Yuan JY (2003) A decade of caspases. Oncogene 22(53):8543–8567. https://doi.org/10.1038/sj.onc.1207107

    Article  CAS  PubMed  Google Scholar 

  36. Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25(34):4798–4811. https://doi.org/10.1038/sj.onc.1209608

    Article  CAS  PubMed  Google Scholar 

  37. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P (2004) Toxic proteins released from mitochondria in cell death. Oncogene 23(16):2861–2874. https://doi.org/10.1038/sj.onc.1207523

    Article  CAS  PubMed  Google Scholar 

  38. Scorei R, Ciubar R, Ciofrangeanu CM, Mitran V, Cimpean A, Iordachescu D (2008) Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biol Trace Elem Res 122(3):197–205. https://doi.org/10.1007/s12011-007-8081-8

    Article  CAS  PubMed  Google Scholar 

  39. Carper SW, Hall C, Adebayo J, Vo V, Meacham SL (2006) Boric acid induces apoptosis in the prostate cancer cell line DU-145 via a caspase 3 dependent mechanism. FASEB J 20(4):A194-A

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey

    Dilek Bayram, Meltem Özgöçmen & Murat Sevimli

  2. Department of Medical Biology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey

    Dilek Aşcı Çelik

  3. Department of Histology and Embryology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyon, Turkey

    Emine Sarman

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Dilek Bayram was responsible for designing the Project, funding acquisition; and writing the manuscript. Dilek Bayram, Meltem Özgöçmen, Dilek Aşçı Çelik, and Emine Sarman were responsible for laboratory analyses. Dilek Bayram and Murat Sevimli made critical revisions to the manuscript. In addition; the English writing language was edited by Scribendi.

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Bayram, D., Özgöçmen, M., Çelik, D.A. et al. Does Boric Acid Inhibit Cell Proliferation on MCF-7 and MDA-MB-231 Cells in Monolayer and Spheroid Cultures by Using Apoptosis Pathways?. Biol Trace Elem Res 202, 2008–2021 (2024). https://doi.org/10.1007/s12011-023-03810-0

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