Effects of resveratrol and 1,3-bis(2-chloroethyl)-1-nitrosurea combination on YKG1 glioblastoma cells

Yıl 2021, , 51 - 57, 15.05.2021

Gökhan Pektaş , Esra Aslan , Hilal Güzel , Betül Demirciler Yavaş , Sefa Çelik

https://doi.org/10.30616/ajb.893690

Öz

Glioblastoma is a primary malignant brain tumor that can be treated with 1,3-bis(2-chloroethyl)-1-nitrosurea (BiCNU/carmustine). Resveratrol is a natural phenol that can interfere with apoptosis. This study aims to investigate how the combination of BiCNU and resveratrol affects glioblastoma cells in vitro. Accordingly, YKG1 glioblastoma cells were treated with different amounts of resveratrol (50 and 100 µM) and BiCNU (10 and 20 µM) either alone or in combination. Cell viability tests and immunochemical studies were conducted on these cells. According to results, increasing the amount of resveratrol and BiCNU decreased cell viability. Additionally, when these maximal doses of resveratrol and BiCNU (100 µM resveratrol plus 20 µM BiCNU) were applied, viability decreased to the highest cytotoxicity levels. Immunohistochemical analysis also revealed the significantly upregulated H scores of beclin-1 and caspase-3 in treated groups with the highest value in maximally combined concentration. These results indicated the cumulative effects of concurrent administration of BiCNU and resveratrol on the cytotoxicity of malignant human YKG1 glioblastoma cells in vitro.

Anahtar Kelimeler

Apoptosis, Carmustine, Glioblastoma, Resveratrol

Destekleyen Kurum

Scientific Research Projects Unit of Afyon Kocatepe University

Proje Numarası

17.KARİYER.171

Teşekkür

The Scientific Research Projects Unit of Afyon Kocatepe University (Grant no: 17.KARİYER.171) funded this study.

Resveratrol ve 1,3-bis(2-kloroetil)-1-nitrozüre kombinasyonunun YKG1 glioblastoma hücreleri üzerine etkileri

Öz

Glioblastoma, 1,3-bis (2-kloroetil) -1-nitrosüre (BiCNU / carmustin) ile tedavi edilebilen birincil kötü huylu beyin tümörüdür. Resveratrol, apoptozu engelleyebilen doğal bir fenoldür. Bu çalışma, BiCNU ve resveratrol kombinasyonunun glioblastoma hücrelerini in vitro nasıl etkilediğini araştırmayı amaçlamaktadır. Çalışma kapsamında glioblastoma YKG1 hücreleri, tek başına veya kombinasyon halinde farklı miktarlarda resveratrol (50 ve 100 uM) ve BiCNU (10 ve 20 uM) ile muamele edildi. Bu hücreler üzerinde hücre canlılığı testleri ve immünokimyasal çalışmalar yapıldı. Sonuçlara göre, resveratrol ve BiCNU miktarının artırılması hücre canlılığını kademeli olarak azalttı. Ek olarak, maksimum resveratrol ve BiCNU dozu (100 µM resveratrol artı 20 µM BiCNU) verildiğinde, hücre canlılıkları oldukça azaldı. İmmünohistokimyasal analizler, maksimum kombine konsantrasyonda muamele edilen gruplarda beklin-1 ve kaspaz-3 H skorları düzeylerini önemli ölçüde arttırdığını ortaya çıkarmıştır. Bu sonuçlar, BiCNU ve resveratrolün aynı anda uygulanmasının, malign insan YKG1 glioblastoma hücrelerinin in vitro sitotoksisitesi üzerindeki kümülatif etkilerini göstermiştir.

Anahtar Kelimeler

Apoptozis, Karmustin, Glioblastoma, Resveratrol

Proje Numarası

17.KARİYER.171

Kaynakça

• Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK, Bigner DD (2009). Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opinion of Investig Drugs 18(8): 1061-1083.
• Afaq F, Adhami VM, Ahmad N (2003). Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice. Toxicology and Applied Pharmacology 186(1): 28-37.
• Alexander BM, Cloughesy TF (2017). Adult Glioblastoma. Journal of Clinical Oncology 35(21): 2402-2409.
• Alifieris C, Trafalis DT (2015). Glioblastoma multiforme: Pathogenesis and treatment. Pharmacology and Therapeutics 152: 63-82.
• Anjum K, Shagufta BI, Abbas SQ, Patel S, Khan I, Shah SAA, Akhter N, Hassan SSU (2017). Current status and future therapeutic perspectives of glioblastoma multiforme (GB) therapy: A review. Biomedicine and Pharmacotherapy 92: 681-689.
• Batash R, Asna N, Schaffer P, Francis N, Schaffer M (2017). Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review. Current Medicinal Chemistry 24(27): 3002-3009.
• Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Research 70(22): 9003-9011.
• Cilibrasi C, Riva G, Romano G, Cadamuro M, Bazzoni R, Butta V, Paoletta L, Dalprá L, Strazzabosco M, Lavitrano M, Giavannonni R, Bentivegna A (2017). Resveratrol impairs glioma stem cells proliferation and motility by modulating the wnt signaling pathway. PLoS One 12(1): e0169854.
• Crusz SM, Balkwill FR (2015). Inflammation and cancer: advances and new agents. Natural Reviews Clinical Oncology 12(10): 584-596.
• Desai K, Hubben A, Ahluwalia M (2019). The Role of Checkpoint Inhibitors in Glioblastoma.Targeted Oncology 14(4): 375-394.
• Emsen B, Turkez H (2017). The protective role of resveratrol against zinc oxide induced nanotoxicity. Anatolian Journal of Botany 1(2): 21-25.
• Filippi-Chiela EC, Villodre ES, Zamin LL, Lenz G (2011). Autophagy interplay with apoptosis and cell cycle regulation in the growth-inhibiting effect of resveratrol in glioma cells. PLoS One 6(6): e20849.
• Firouzi F, Khoei S, Mirzaei HR (2015). Role of resveratrol on the cytotoxic effects and DNA damages of iododeoxyuridine and megavoltage radiation in spheroid culture of U87MG glioblastoma cell line. General Physiology and Biophysics 34(1): 43-50.
• Goldberg DM, Yan J, Soleas GJ (2003). Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clinical Biochemistry 36(1): 79-87.
• Hart MG, Grant R, Garside R, Rogers G, Somerville M, Stein K (2011). Chemotherapy wafers for high grade glioma. Cochrane Database Systematic Review 1(3): CD007294.
• Huang L, Mellor AL (2014). Metabolic control of tumour progression and antitumour immunity. Current Opinion in Oncology 26(1): 92-99.
• Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275(5297): 218-220.
• Kaczanowski S (2016). Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Physical Biology 13(3): 031001.
• Kaldas MI, Walle UK, Walle T (2003). Resveratrol transport and metabolism by human intestinal Caco-2 cells. Journal of Pharmacy and Pharmacology 55(3): 307-312.
• Kataria R, Khatkar A (2019). Resveratrol in Various Pockets: A Review. Current Topics in Medicinal Chemistry 19(2): 116-22.
• Kundu JK, Surh YJ (2008). Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Letters 269(2): 243-261.
• Le Corre L, Chalabi N, Delort L, Bignon YJ, Bernard-Gallon DJ (2005). Resveratrol and breast cancer chemoprevention: molecular mechanisms. Mol Nutrition and Food Research 49(5): 462-471.
• Lopez J, Tait SW (2015). Mitochondrial apoptosis: killing cancer using the enemy within. British Journal of Cancer 112(6): 957-962.
• Nagpal S (2102). The role of BCNU polymer wafers (Gliadel) in the treatment of malignant glioma. Neurosurgery Clinics of North America 23: 289-295.
• Omuro A, DeAngelis LM (2013). Glioblastoma and other malignant gliomas: A clinical review. Journal of American Medical Association 310(17): 1842-1850.
• Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA, Brenner DE, Steward WP, Gescher AJ, Brown K (2010). Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Research 70(19): 7392-7399.
• Perry J, Chambers A, Spithof K, Laperriere N (2007). Gliadel wafers in the treatment of malignant glioma: A systematic review. Current Oncology 14: 189-194.
• Rauf A, Imran M, Butt MS, Nadeem M, Peters DG, Mubarak MS (2018). Resveratrol as an anti-cancer agent: A review. Critical Reviews in Food Science and Nutrition 58(9): 1428-1447.
• Reagan-Shaw S, Afaq F, Aziz MH, Ahmad N (2004). Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. Oncogene 23(30): 5151-5160.
• Shukla Y, Singh R (2011). Resveratrol and cellular mechanisms of cancer prevention. Annals of the New York Academy of Sciences 1215: 1-8.
• Soleas GJ, Angelini M, Grass L, Diamandis EP, Goldberg DM (2001). Absorption of trans-resveratrol in rats. Methods in Enzymology 335: 145-154.
• Song Y, Chen Y, Li Y, Lyu X, Cui J, Cheng Y, Zheng T, Zhao L, Zhao G (2019). Resveratrol Suppresses Epithelial-Mesenchymal Transition in GB by Regulating Smad-Dependent Signaling. Biomed Research International 2019: 1321973.
• Spiegel BM, Esrailian E, Laine L, Chamberlain MC (2007). Clinical impact of adjuvant chemotherapy in glioblastoma multiforme: A meta-analysis. Central Nervous System Drugs 21: 775-787.
• Stoyanov GS, Dzhenkov D, Ghenev P, Iliev B, Enchev Y, Tonchev AB (2018). Cell biology of glioblastoma multiforme: from basic science to diagnosis and treatment. Medical Oncology 35(3): 27.
• Tian M, Ma W, Chen Y, Yu Y, Zhu D, Shi J, Zhang Y (2018). Impact of gender on the survival of patients with glioblastoma. Bioscience Reports 38(6): BSR20180752.
• Vervandier-Fasseur D, Latruffe N (2019). The Potential Use of Resveratrol for Cancer Prevention. Molecules 24(24): 4506.
• Villà S, Balañà C, Comas S (2014). Radiation and concomitant chemotherapy for patients with glioblastoma multiforme. Chinese Journal of Cancer 33(1): 25-31.
• Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition 32(12): 1377-1382.
• Wenzel E, Somoza V (2005). Metabolism and bioavailability of trans-resveratrol. Molecular Nutrition and Food Research 49(5): 472-481.
• Williams DS (2014). Glioblastoma multiforme. Journal of Insurance Medicine 44(1): 62-64.
• Witthayanuwat S, Pesee M, Supaadirek C, Supakalin N, Thamronganantasakul K, Krusun S (2018). Survival Analysis of Glioblastoma Multiforme. Asian Pacific Journal of Cancer Prevention 19(9): 2613-2617.
• Xiao ZZ, Wang ZF, Lan T, Huang WH, Zhao YH, Ma C, Li ZQ (2020). Carmustine as a Supplementary Therapeutic Option for Glioblastoma: A Systematic Review and Meta-Analysis. In Frontiers in Neurology 11: 1036.
• Xu GW, Mymryk JS, Cairncross JG (2005). Pharmaceutical-mediated inactivation of p53 sensitizes U87MG glioma cells to BCNU and temozolomide. International Journal of Cancer 116(2): 187-192.
• Yang Y, Cui J, Xue F, Overstreet AM, Zhan Y, Shan D, Li H, Li H, Wang Y, Zhang M, Yu C, Xu ZD (2016). Resveratrol represses pokemon expression in human glioma cells. Molecular Neurobiology 53(2): 1266-1278.
• Yu C, Shin YG, Chow A, Li Y, Kosmeder JW, Lee YS, Hirschelman WH, Pezzuto JM, Mehta RG, van Breemen RB (2002). Human, rat, and mouse metabolism of resveratrol. Pharmacological Research 19(12): 1907-1914.
• Zhang YD, Dai RY, Chen Z, Zhang YH, He XZ, Zhou J (2014). Efficacy and safety of carmustine wafers in the treatment of glioblastoma multiforme: a systematic review. Turkish Neurosurgery 24(5): 639-645.