Boric Acid Treatment Strengthens the Cytotoxic Effect of Sorafenib on Triple Negative Breast Cancer Cell Lines

Year 2023, Volume: 19 Issue: 2, 137 - 141, 29.06.2023

Erkan Kahraman , Erdem Göker

Abstract

In recent years, it has been demonstrated that combinational therapies have shown promising results in the treatment of triple negative breast cancer. However, the effect of the sequential combination of sorafenib with boric acid on cell viability in triple negative breast cancer cell lines is unknown. Thus, the present study aims to investigate the effects of sequential treatment of boric acid and sorafenib on cell viability in triple negative breast cancer cell lines. MDA-MB-231 cells were used in our study. Sorafenib was treated to the cells at a dose range of 0.5-16µM, and boric acid at 1-160mM. Changes in cell viability were determined using by MTT analysis at 24,48 and 72 hours. Cell viability decreased statistically significantly at 4µM and above doses of sorafenib, and 5mM and above doses of boric acid (p<0.05). IC50 values of boric acid were calculated as 34mM, 26mM and 1mM at hours 24,48 and 72, respectively. Alone treatment of sorafenib at 8µM and 16µM doses reduced cell viability up to 80% and 61%, respectively. On the other hand, 15mM boric acid treatment followed by sorafenib treatment at 8µM and 16µM doses decreased cell viability up to 64% and 44%, respectively (p<0.05). Also, it was observed that boric acid treatment followed by sorafenib treatment caused MDA-MB-231 cells to diverge from their ancestral morphology, resulting in an unhealthier appearance. Our results suggest that a sequential treatment of boric acid followed by sorafenib strengthens the cytotoxic effect of sorafenib on triple negative breast cancer cell lines.

Keywords

Boric Acid, Boron, Sorafenib, Triple negative breast cancer

Thanks

We would like to thank Academic Oncology Association from Turkey for funding support.

References

• Bray F, Ferlay J, Soerjomataram I, et al. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians; 68: 394-424.
• Weigelt B, Geyer FC, Reis-Filho JS. 2010. Histological types of breast cancer: How special are they? Molecular Oncology; 4: 192-208.
• Garrido-Castro AC, Lin NU, Polyak K. 2019. Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for TreatmentHeterogeneity of Triple- Negative Breast Cancer. Cancer discovery; 9: 176-198.
• Yin L, Duan J-J, Bian X-W, et al. 2020. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Research; 22: 61.
• Chalakur-Ramireddy Naveen KR, Pakala Suresh B. 2018. Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer. Bioscience Reports; 38: BSR20171357.
• Llovet JM, Ricci S, Mazzaferro V, et al. 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med; 359: 378-390.
• Wilhelm SM, Carter C, Tang L, et al. 2004. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res; 64: 7099-7109.
• Marisi G, Cucchetti A, Ulivi P, et al. 2018. Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers? World J Gastroenterol; 24: 4152-4163.
• Moreno-Aspitia A. 2010. Clinical overview of sorafenib in breast cancer. Future Oncology; 6: 655-663.
• Bianchi G, Loibl S, Zamagni C, et al. 2009. Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. Anti-Cancer Drugs; 20: 616-624.
• Kot FS. 2009. Boron sources, speciation and its potential impact on health. Reviews in Environmental Science and Bio/Technology; 8: 3-28.
• Smallwood C. International Programme on Chemical Safety Environmental Health Criteria 204 Boron; WHO: Geneva, 1998;
• Barranco W, Eckhert C. 2006. Cellular changes in boric acid- treated DU-145 prostate cancer cells. British journal of cancer; 94: 884-890.
• Cui Y, Winton MI, Zhang Z-F, et al. 2004. Dietary boron intake and prostate cancer risk. Oncol Rep; 11: 887-892.
• Kahraman E, Göker E. 2022. Boric acid exert anti-cancer effect in poorly differentiated hepatocellular carcinoma cells via inhibition of AKT signaling pathway. Journal of Trace Elements in Medicine and Biology; 73: 127043.
• Kahraman E, Gürhan İD, Korkmaz M. 2013. Investigation of possible genotoxic and cytotoxic effects of differential boron compounds in ccl 62 (hela contaminant) human amniotic ephitelial cell line. Medicine Science; 2: 454-468.
• Meacham SL, Hall C, Tharkar S, et al. Boric acid induces apoptosis in some breast cancer cell lines. In.: Wiley Online Library; 2006.
• Lebert JM, Lester R, Powell E, et al. 2018. Advances in the Systemic Treatment of Triple-Negative Breast Cancer. Current Oncology; 25: 142-150.
• Nedeljković M, Damjanović A. 2019. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge. Cells; 8: 957.
• Wahba HA, El-Hadaad HA. 2015. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med; 12: 106- 116.
• Zafrakas M, Papasozomenou P, Emmanouilides C. 2016. Sorafenib in breast cancer treatment: A systematic review and overview of clinical trials. World J Clin Oncol; 7: 331-336.
• Bronte G, Andreis D, Bravaccini S, et al. 2017. Sorafenib for the treatment of breast cancer. Expert Opinion on Pharmacotherapy; 18: 621-630.
• Wei J-c, Meng F-d, Qu K, et al. 2015. Sorafenib inhibits proliferation and invasion of human hepatocellular carcinoma cells via up-regulation of p53 and suppressing FoxM1. Acta Pharmacologica Sinica; 36: 241-251.
• Oh SJ, Erb HH, Hobisch A, et al. 2012. Sorafenib decreases proliferation and induces apoptosis of prostate cancer cells by inhibition of the androgen receptor and Akt signaling pathways. Endocr Relat Cancer; 19: 305-319.
• Dattachoudhury S, Sharma R, Kumar A, et al. 2020. Sorafenib inhibits proliferation, migration and invasion of breast cancer cells. Oncology; 98: 478-486.
• Aydin HE, Koldemir-Gündüz M, Kizmazoglu C, et al. 2021. Cytotoxic effect of boron application on glioblastoma cells. Turk Neurosurg; 31: 206-210.
• Hacioglu C, Kar F, Kacar S, et al. 2020. High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line. Biological Trace Element Research; 193: 400-409.
• Lee A, Djamgoz MBA. 2018. Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies. Cancer Treatment Reviews; 62: 110-122.
• Gradishar WJ, Kaklamani V, Sahoo TP, et al. 2013. A double- blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer. European Journal of Cancer; 49: 312-322.
• Baselga J, Segalla JGM, Roché H, et al. 2012. Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer. Journal of Clinical Oncology; 30: 1484-1491.