The Protective Effects of Sodium Pentaborate Tetrahydrate Against UVB-induced Apoptosis in Human Keratinocytes

Year 2022, Volume: 9 Issue: 3, 213 - 218, 28.09.2022

Ezgi Avşar Abdik

https://doi.org/10.17350/HJSE19030000273

Abstract

Ultraviolet radiation (UV) is an environmental carcinogen causing human skin cancer. Exposure of the skin to UV produces apoptotic keratinocytes called sunburn cells within the epidermis. Boron, an essential element for plants, has several biological properties, such as anti-cancer, anti-microbial, and anti-oxidant. In the present study, the possible protective effects of sodium pentaborate pentahydrate (SPT) against UVB-induced apoptosis in human keratinocyte cells, HaCaT, were investigated. They were treated with SPT at different concentrations (7.8-125 μg/mL) for 24h after UVB irradiation (20, 30 and 60mJ/cm2). Cell viability, annexin V assay, cell cycle analysis, and apoptosis-related gene levels were measured using RT-PCR. Treatment with SPT (15.6-31.25μg/mL) after 30 mJ/m2 UVB exposure significantly increased cell survival. Annexin V apoptosis analysis demonstrated a robust protective effect by treatment with SPT at concentrations of 15.6 and 31.25μg/mL after 30mJ/cm2 UVB irradiation. The cell cycle analysis revealed that UVB irradiation elevated the number of cells at the G0/G1 phase while SPT treatment after UVB irradiation increased the number of cells at G2/M phase, suggesting the changes were partially reversed. Furthermore, treatment with 15.6μg/mL SPT after 30 mJ/m2 UV irradiation blocked the activation of caspase 3, caspase 9, Bax, and p53. These results indicate that treatment with SPT exerts protective effects after UVB irradiation. Thus, treatment with SPT led to strong protection against UVB-induced apoptotic cell death in HaCaT cells.

Keywords

Sodium pentaborate pentahydrate, UVB irradiation, Apoptosis, Keratinocyte

Thanks

This study was supported by Yeditepe University.

References

• D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. International journal of molecular sciences 14 (2013) 12222–48.
• Koster MI. Making an epidermis. Annals of the New York Academy of Sciences 1170 (2009) 7–10.
• Chang SH, Liu JY, Hsiao MW, Yang HL, Wang GW, Ye JC. Protective effects of Ocimum gratissimumAqueous extracts on HaCaT cells against UVC-induced inhibition of cell viability and migration. International Journal of Medical Sciences 18 (2021) 2086.
• Pfeifer GP, Besaratinia A. UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 11 (2012) 90–7.
• Girotti AW. Lipid hydroperoxide generation, turnover, and effector action in biological systems. Journal of lipid research 39 (1998) 1529–42.
• Shih MF, Cherng JY. Protective effects of Chlorella-derived peptide against UVC-induced cytotoxicity through inhibition of caspase-3 activity and reduction of the expression of phosphorylated FADD and cleaved PARP-1 in skin fibroblasts. Molecules (Basel, Switzerland) 17 (2012) 9116–28.
• Wang SC, Chen SF, Lee YM, Chuang CL, Bau DT, Lin SS. Baicalin scavenges reactive oxygen species and protects human keratinocytes against UVC-induced cytotoxicity. In vivo (Athens, Greece) 27 (2013) 707–14.
• Kim HB, Yoo BS. Propolis inhibits UVA-induced apoptosis of human keratinocyte HaCaT cells by scavenging ROS. Toxicological Research 32 (2016) 345–51.
• Benchimol S. p53-dependent pathways of apoptosis. Cell death and differentiation 8 (2001) 1049–51.
• Dogan A, Demirci S, Çaglayan AB, Kiliç E, Günal MY, Uslu Ü, Cumbul A, Sahin F. Sodium pentaborate pentahydrate and pluronic containing hydrogel increases cutaneous wound healing in vitro and in vivo. Biological trace element research 162 (2014) 72–9.
• Khaliq H, Juming Z, Ke-Mei P. The Physiological Role of Boron on Health. Biological Trace Element Research 186 (2018) 31–51.
• Sogut I, Paltun SO, Tuncdemir M, Ersoz M, Hurdag C. The antioxidant and antiapoptotic effect of boric acid on hepatoxicity in chronic alcohol-fed rats. Canadian journal of physiology and pharmacology 96 (2018) 404–11.
• Sogut I, Oglakci A, Kartkaya K, Ol KK, Sogut MS, Kanbak G, Inal ME. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Experimental and therapeutic medicine 9 (2015) 1023–7.
• Benderdour M, Van Bui T, Hess K, Dicko A, Belleville F, Dousset B. Effects of boron derivatives on extracellular matrix formation. Journal of trace elements in medicine and biology 14 (2000) 168–73.
• Alak G, Parlak V, Yeltekin AÇ, Ucar A, Çomakli S, Topal A, Atamanalp M, Özkaraca M, Türkez H. The protective effect exerted by dietary borax on toxicity metabolism in rainbow trout (Oncorhynchus mykiss) tissues. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 216 (2019) 82–92.
• Turkez H, Geyikoglu F. Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood. Cytotechnology 62 (2010) 157–65.
• Cebeci E, Yüksel B, Sahin F. Anti-cancer effect of boron derivatives on small-cell lung cancer. Journal of Trace Elements in Medicine and Biology 70 (2022) 126923.
• Abdik H. Combined effects of zoledronic acid and sodium pentaborate pentahydrate on proliferation, migration and apoptosis of human neuroblastoma cell line. Middle East Journal of Science 7 (2021) 24–35.
• Li LH, Wu LJ, Tashiro S ichi, Onodera S, Uchiumi F, Ikejima T. Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of caspase-8 pathway. Biological and Pharmaceutical Bulletin 29 (2006) 1096–101.
• Mohammadzadeh S, Sharriatpanahi M, Hamedi M, Amanzadeh Y, Ebrahimi SES, Ostad SN. Antioxidant power of Iranian propolis extract. Food chemistry 103 (2007) 729–33.
• Kumazawa S, Hamasaka T, Nakayama T. Antioxidant activity of propolis of various geographic origins. Food chemistry 84 (2004) 329–39.
• Lang PA, Parkova A, Leissing TM, Calvopiña K, Cain R, Krajnc A, Panduwawala TD, Philippe J, Fishwick CWG, Trapencieris P, Page MGP, Schofield CJ, Brem J. Bicyclic boronates as potent inhibitors of AmpC, the class C $β$-lactamase from Escherichia coli. Biomolecules 10 (2020) 899.
• Beer LC, Vuong CN, Barros TL, Latorre JD, Tellez G, Fuller AL, Hargis BM. Research Note: Evaluation of boric acid as a chemoprophylaxis candidate to prevent histomoniasis. Poultry science 99 (2020) 1978–82.
• Maslah H, Skarbek C, Pethe S, Labruère R. Anticancer boron-containing prodrugs responsive to oxidative stress from the tumor microenvironment. European Journal of Medicinal Chemistry 207 (2020) 112670.
• Türkez H, Arslan ME, Sönmez E, Tatar A, Açikyildiz M, Geyikoglu F. Toxicogenomic responses of human alveolar epithelial cells to tungsten boride nanoparticles. Chemico-Biological Interactions 273 (2017) 257–65.
• Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Demirel HH, Kucukkurt I, Eryavuz A, Kara R, Varol N, Zhu K. Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: protective role of boron. Toxicology research 8 (2019) 262–9.
• Çelikezen FÇ, Turkez H, Togar B, Izgi MS. DNA damaging and biochemical effects of potassium tetraborate. EXCLI journal 13 (2014) 446.
• Ayhanci A, Tanriverdi DT, Sahinturk V, Cengiz M, Appak-Baskoy S, Sahin IK. Protective effects of boron on cyclophosphamide-induced bladder damage and oxidative stress in rats. Biological trace element research 197 (2020) 184–91.
• Lu L, Zhang Q, Ren M, Jin E, Hu Q, Zhao C, Li S. Effects of Boron on Cytotoxicity, Apoptosis, and Cell Cycle of Cultured Rat Sertoli Cells In vitro. Biological Trace Element Research 196 (2020) 223–30.
• Moon JY, Lee EJ, Yoo BS. Propolis Protects Human Keratinocyte HaCaT Cells against UV-induced Apoptosis. Journal of Apiculture 27 (2012) 243–9.
• Fischer TW, Zbytek B, Sayre RM, Apostolov EO, Basnakian AG, Sweatman TW, Wortsman J, Elsner P, Slominski A. Melatonin increases survival of HaCaT keratinocytes by suppressing UV-induced apoptosis. Journal of pineal research 40 (2006) 18–26.
• Murphy G, Young AR, Wulf HC, Kulms D, Schwarz T. The molecular determinants of sunburn cell formation. Experimental dermatology 10 (2001) 155–60.
• Schwarz A, Ständer S, Berneburg M, Böhm M, Kulms D, van Steeg H, Grosse-Heitmeyer K, Krutmann J, Schwarz T. Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. Nature cell biology 4 (2002) 26–31.
• Gillardon F, Moll I, Meyer M, Michaelidis TM. Alterations in cell death and cell cycle progression in the UV-irradiated epidermis of bcl-2-deficient mice. Cell Death & Differentiation 6 (1999) 55–60.
• Taylor JK, Zhang QQ, Monia BP, Marcusson EG, Dean NM. Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli. Oncogene 18 (1999) 4495–504.
• Katagiri C, Nakanishi J, Kadoya K, Hibino T. Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH2-terminal kinase. The Journal of cell biology 172 (2006) 983–90.
• Yoshihisa Y, Rehman MU, Shimizu T. Astaxanthin, a xanthophyll carotenoid, inhibits ultraviolet-induced apoptosis in keratinocytes. Experimental dermatology 23 (2014) 178–83.
• Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nature medicine 3 (1997) 614–20.
• Terazawa S, Nakajima H, Shingo M, Niwano T, Imokawa G. Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner. Experimental dermatology 21 Suppl 1 (2012) 11–7.
• Song X dong, Zhang J jin, Wang M rong, Liu W bo, Gu X bin, Lv CJ. Astaxanthin induces mitochondria-mediated apoptosis in rat hepatocellular carcinoma CBRH-7919 cells. Biological & pharmaceutical bulletin 34 (2011) 839–44.
• Vousden KH, Lu X. Live or let die: the cell’s response to p53. Nature Reviews Cancer 2 (2002) 594–604.
• Latonen L, Laiho M. Cellular UV damage responses—Functions of tumor suppressor p53. Biochimica et Biophysica Acta (BBA) -Reviews on Cancer 1755 (2005) 71–89.
• Prives C, Hall PA. The p53 pathway. The Journal of pathology 187 (1999) 112–26.
• Cengiz M, Sahinturk V, Yildiz SC, Şahin İK, Bilici N, Yaman SO, Altuner Y, Appak-Basköy S, Ayhanci A . Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron. Journal of Trace Elements in Medicine and Biology 62 (2020) 126574.