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A Comparative Study of the Antiproliferative and Apoptotic Effects of Some Chemotherapeutic Drugs on Neuroblastoma Cells

Yıl 2023, , 634 - 641, 28.09.2023
https://doi.org/10.17798/bitlisfen.1258011

Öz

In this study, it was aimed to investigate the antiproliferative and apoptotic effects of nivolumab, cetuximab and gemcitabine used in the treatment of different cancer types as well as cisplatin and cyclophosphamide used in the treatment of neuroblastoma on SH-SY5Y neuroblastoma cells. The effect of each chemotherapeutic on cell viability and the individual IC50 values were determined by the crystal violet method. To determine their apoptotic effects, RT-PCR and Annexin V-FITC apoptosis detection technique were used. The results indicated that all the used chemotherapeutic drugs showed dose-dependent cytotoxic effects and induced apoptosis in SH-SY5Y cells. The IC50 values of cisplatin, cyclophosphamide, nivolumab, cetuximab, and gemcitabine were calculated as 10.91 µM, 0.54 µM, 30.26 μM 4.74 μM and 0.036 μM, respectively. After IC50 dose treatment of cisplatin, cyclophosphamide, nivolumab, cetuximab, and gemcitabine apoptotic cell rates were found as 21%, 12%, 16%, 10% and 39% respectively. It was determined that statistically significant changes in mRNA expression levels in almost all apoptosis-related genes occurred after chemotherapeutic drugs treatment. In conclusion, gemcitabine showed more antiproliferative and apoptotic effects on neuroblastoma cells than the other chemotherapeutics. It is clear that further studies that will elucidate the mechanism of action of gemcitabine may contribute to the treatment of neuroblastoma.

Kaynakça

  • [1] C. Pudela, S. Balyasny, and M. A. Applebaum, “Nervous system: Embryonal tumors: Neuroblastoma,” Atlas Genet. Cytogenet. Oncol. Haematol., vol. 24, no. 7, pp. 284–290, 2020.
  • [2] E. S. Hanemaaijer et al., “Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype,” Proc. Natl. Acad. Sci. U. S. A., vol. 118, no. 5, p. e2022350118, 2021.
  • [3] I. V. Kholodenko, D. V. Kalinovsky, I. I. Doronin, S. M. Deyev, and R. V. Kholodenko, “Neuroblastoma origin and therapeutic targets for immunotherapy,” J. Immunol. Res., vol. 2018, pp. 1–25, 2018.
  • [4] E. S.-W. Ngan, “Heterogeneity of neuroblastoma,” Oncoscience, vol. 2, no. 10, pp. 837–838, 2015.
  • [5] N.-K. V. Cheung and M. A. Dyer, “Neuroblastoma: developmental biology, cancer genomics and immunotherapy,” Nat. Rev. Cancer, vol. 13, no. 6, pp. 397–411, 2013.
  • [6] V. P. Tolbert and K. K. Matthay, “Neuroblastoma: clinical and biological approach to risk stratification and treatment,” Cell Tissue Res., vol. 372, no. 2, pp. 195–209, 2018.
  • [7] J. Blatt and R. L. Hamilton, “Neurodevelopmental anomalies in children with neuroblastoma,” Cancer, vol. 82, no. 8, pp. 1603–1608, 1998.
  • [8] J. A. Tomolonis, S. Agarwal, and J. M. Shohet, “Neuroblastoma pathogenesis: deregulation of embryonic neural crest development,” Cell Tissue Res., vol. 372, no. 2, pp. 245–262, 2018.
  • [9] M. S. Irwin and J. R. Park, “Neuroblastoma: paradigm for precision medicine,” Pediatr. Clin. North Am., vol. 62, no. 1, pp. 225–256, 2015.
  • [10] I. Janoueix-Lerosey et al., “Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma,” Nature, vol. 455, no. 7215, pp. 967–970, 2008.
  • [11] S. Gómez, G. Castellano, G. Mayol, A. Queiros, J. I. Martín-Subero, and C. Lavarino, “DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights,” Genom. Data, vol. 5, pp. 360–363, 2015.
  • [12] E. Sokol and A. V. Desai, “The evolution of risk classification for neuroblastoma,” Children (Basel), vol. 6, no. 2, p. 27, 2019.
  • [13] K. K. Matthay et al., “Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group,” N. Engl. J. Med., vol. 341, no. 16, pp. 1165–1173, 1999.
  • [14] J. M. Maris, “Recent advances in neuroblastoma,” N. Engl. J. Med., vol. 362, no. 23, pp. 2202–2211, 2010.
  • [15] H. Richard, A. Pokhrel, S. Chava, A. Pathania, S. S. Katta, and K. B. Challagundla, “Exosomes: Novel players of therapy resistance in neuroblastoma,” Adv. Exp. Med. Biol., vol. 1277, pp. 75–85, 2020.
  • [16] P. Bhoopathi, P. Mannangatti, L. Emdad, S. K. Das, and P. B. Fisher, “The quest to develop an effective therapy for neuroblastoma,” J. Cell. Physiol., vol. 236, no. 11, pp. 7775–7791, 2021.
  • [17] L. Heinonen and B. Sandberg, “Money for nothing? Risks in biopharmaceutical companies from the perspective of public financiers,” J. Commer. Biotechnol., vol. 14, no. 4, 2008.
  • [18] Y. Morofuji and S. Nakagawa, “Drug development for central nervous system diseases using in vitro blood-brain barrier models and drug repositioning,” Curr. Pharm. Des., vol. 26, no. 13, pp. 1466–1485, 2020.
  • [19] S. Zuo et al., “Potential role of the PD-L1 expression and tumor-infiltrating lymphocytes on neuroblastoma,” Pediatr. Surg. Int., vol. 36, no. 2, pp. 137–143, 2020.
  • [20] S. Tamura et al., “Induction of apoptosis by an inhibitor of EGFR in neuroblastoma cells,” Biochem. Biophys. Res. Commun., vol. 358, no. 1, pp. 226–232, 2007.
  • [21] M. Ogawa, H. Hori, T. Ohta, K. Onozato, M. Miyahara, and Y. Komada, “Sensitivity to gemcitabine and its metabolizing enzymes in neuroblastoma,” Clin. Cancer Res., vol. 11, no. 9, pp. 3485–3493, 2005.
  • [22] G. Celik, H. Akca, and A. Sen, “Investigation of aromotase inhibition by several dietary vegetables in human non-small cell lung cancer cell lines,” Turk. J. Bioch., vol. 38, no. 2, pp. 207–217, 2013.
  • [23] M. Sulak, G. C. Turgut, and A. Sen, “Cerium oxide nanoparticles biosynthesized using fresh green walnut shell in microwave environment and their anticancer effect on breast cancer cells,” Chem. Biodivers., vol. 19, no. 8, p. e202200131, 2022.
  • [24] I. Erdogan Orhan et al., “Evaluation of anti-Alzheimer activity of synthetic coumarins by combination of in vitro and in silico approaches,” Chem. Biodivers., vol. 19, no. 12, p. e202200315, 2022.
  • [25] C. Sahin et al., “New iridium bis-terpyridine complexes: synthesis, characterization, antibiofilm and anticancer potentials,” Biometals, vol. 34, no. 3, pp. 701–713, 2021.
  • [26] E. Yilmaz, M. B. Samur, A. Özcan, E. Ünal, and M. Karakükçü, “Transplantation for ultra high-risk neuroblastoma patients: effect of tandem autologous stem cell transplantation,” J. Health Sci. Med., vol. 4, no. 6, pp. 943–948, 2021.
  • [27] V. Smith and J. Foster, “High-risk neuroblastoma treatment review,” Children (Basel), vol. 5, no. 9, 2018.
  • [28] A. Zafar et al., “Molecular targeting therapies for neuroblastoma: Progress and challenges,” Med. Res. Rev., vol. 41, no. 2, pp. 961–1021, 2021.
  • [29] S. Mallepalli, M. K. Gupta, and R. Vadde, “Neuroblastoma: An updated review on biology and treatment,” Curr. Drug Metab., vol. 20, no. 13, pp. 1014–1022, 2019.
  • [30] N. W. Mabe et al., “Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1,” Nat. Cancer, vol. 3, no. 8, pp. 976–993, 2022.
  • [31] E. Donzelli et al., “Neurotoxicity of platinum compounds: Comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y,” J. Neurooncol., vol. 67, no. 1/2, pp. 65–73, 2004.
  • [32] W. Álvarez-León, I. Mendieta, E. Delgado-González, B. Anguiano, and C. Aceves, “Molecular iodine/cyclophosphamide synergism on chemoresistant neuroblastoma models,” Int. J. Mol. Sci., vol. 22, no. 16, p. 8936, 2021.
  • [33] L.-M. Sun et al., “Nivolumab effectively inhibit platinum-resistant ovarian cancer cells via induction of cell apoptosis and inhibition of ADAM17 expression,” Eur. Rev. Med. Pharmacol. Sci., vol. 21, no. 6, pp. 1198–1205, 2017.
  • [34] M. Wang and A. Yuang-Chi Chang, “Molecular mechanism of action and potential biomarkers of growth inhibition of synergistic combination of afatinib and dasatinib against gefitinib-resistant non-small cell lung cancer cells,” Oncotarget, vol. 9, no. 23, pp. 16533–16546, 2018.
  • [35] Y. Yamamoto et al., “Cetuximab promotes anticancer drug toxicity in rhabdomyosarcomas with EGFR amplification in vitro,” Oncol. Rep., vol. 30, no. 3, pp. 1081–1086, 2013.
  • [36] M. Tesson, G. Anselmi, C. Bell, and R. Mairs, “Cell cycle specific radiosensitisation by the disulfiram and copper complex,” Oncotarget, vol. 8, no. 39, pp. 65900–65916, 2017.
  • [37] M. Hassan, H. Watari, A. AbuAlmaaty, Y. Ohba, and N. Sakuragi, “Apoptosis and molecular targeting therapy in cancer,” Biomed Res. Int., vol. 2014, p. 150845, 2014.
  • [38] K. Million et al., “Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells,” Int. J. Oncol., vol. 29, no. 1, pp. 147–154, 2006.
  • [39] M. Jiang, X. Yi, S. Hsu, C.-Y. Wang, and Z. Dong, “Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity,” Am. J. Physiol. Renal Physiol., vol. 287, no. 6, pp. F1140-7, 2004.
  • [40] R. Hill et al., “Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy,” Cell Death Dis., vol. 4, no. 9, p. e791, 2013.
  • [41] H. Baysal et al., “Cetuximab-induced natural killer cell cytotoxicity in head and neck squamous cell carcinoma cell lines: investigation of the role of cetuximab sensitivity and HPV status,” Br. J. Cancer, vol. 123, no. 5, pp. 752–761, 2020
Yıl 2023, , 634 - 641, 28.09.2023
https://doi.org/10.17798/bitlisfen.1258011

Öz

Kaynakça

  • [1] C. Pudela, S. Balyasny, and M. A. Applebaum, “Nervous system: Embryonal tumors: Neuroblastoma,” Atlas Genet. Cytogenet. Oncol. Haematol., vol. 24, no. 7, pp. 284–290, 2020.
  • [2] E. S. Hanemaaijer et al., “Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype,” Proc. Natl. Acad. Sci. U. S. A., vol. 118, no. 5, p. e2022350118, 2021.
  • [3] I. V. Kholodenko, D. V. Kalinovsky, I. I. Doronin, S. M. Deyev, and R. V. Kholodenko, “Neuroblastoma origin and therapeutic targets for immunotherapy,” J. Immunol. Res., vol. 2018, pp. 1–25, 2018.
  • [4] E. S.-W. Ngan, “Heterogeneity of neuroblastoma,” Oncoscience, vol. 2, no. 10, pp. 837–838, 2015.
  • [5] N.-K. V. Cheung and M. A. Dyer, “Neuroblastoma: developmental biology, cancer genomics and immunotherapy,” Nat. Rev. Cancer, vol. 13, no. 6, pp. 397–411, 2013.
  • [6] V. P. Tolbert and K. K. Matthay, “Neuroblastoma: clinical and biological approach to risk stratification and treatment,” Cell Tissue Res., vol. 372, no. 2, pp. 195–209, 2018.
  • [7] J. Blatt and R. L. Hamilton, “Neurodevelopmental anomalies in children with neuroblastoma,” Cancer, vol. 82, no. 8, pp. 1603–1608, 1998.
  • [8] J. A. Tomolonis, S. Agarwal, and J. M. Shohet, “Neuroblastoma pathogenesis: deregulation of embryonic neural crest development,” Cell Tissue Res., vol. 372, no. 2, pp. 245–262, 2018.
  • [9] M. S. Irwin and J. R. Park, “Neuroblastoma: paradigm for precision medicine,” Pediatr. Clin. North Am., vol. 62, no. 1, pp. 225–256, 2015.
  • [10] I. Janoueix-Lerosey et al., “Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma,” Nature, vol. 455, no. 7215, pp. 967–970, 2008.
  • [11] S. Gómez, G. Castellano, G. Mayol, A. Queiros, J. I. Martín-Subero, and C. Lavarino, “DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights,” Genom. Data, vol. 5, pp. 360–363, 2015.
  • [12] E. Sokol and A. V. Desai, “The evolution of risk classification for neuroblastoma,” Children (Basel), vol. 6, no. 2, p. 27, 2019.
  • [13] K. K. Matthay et al., “Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group,” N. Engl. J. Med., vol. 341, no. 16, pp. 1165–1173, 1999.
  • [14] J. M. Maris, “Recent advances in neuroblastoma,” N. Engl. J. Med., vol. 362, no. 23, pp. 2202–2211, 2010.
  • [15] H. Richard, A. Pokhrel, S. Chava, A. Pathania, S. S. Katta, and K. B. Challagundla, “Exosomes: Novel players of therapy resistance in neuroblastoma,” Adv. Exp. Med. Biol., vol. 1277, pp. 75–85, 2020.
  • [16] P. Bhoopathi, P. Mannangatti, L. Emdad, S. K. Das, and P. B. Fisher, “The quest to develop an effective therapy for neuroblastoma,” J. Cell. Physiol., vol. 236, no. 11, pp. 7775–7791, 2021.
  • [17] L. Heinonen and B. Sandberg, “Money for nothing? Risks in biopharmaceutical companies from the perspective of public financiers,” J. Commer. Biotechnol., vol. 14, no. 4, 2008.
  • [18] Y. Morofuji and S. Nakagawa, “Drug development for central nervous system diseases using in vitro blood-brain barrier models and drug repositioning,” Curr. Pharm. Des., vol. 26, no. 13, pp. 1466–1485, 2020.
  • [19] S. Zuo et al., “Potential role of the PD-L1 expression and tumor-infiltrating lymphocytes on neuroblastoma,” Pediatr. Surg. Int., vol. 36, no. 2, pp. 137–143, 2020.
  • [20] S. Tamura et al., “Induction of apoptosis by an inhibitor of EGFR in neuroblastoma cells,” Biochem. Biophys. Res. Commun., vol. 358, no. 1, pp. 226–232, 2007.
  • [21] M. Ogawa, H. Hori, T. Ohta, K. Onozato, M. Miyahara, and Y. Komada, “Sensitivity to gemcitabine and its metabolizing enzymes in neuroblastoma,” Clin. Cancer Res., vol. 11, no. 9, pp. 3485–3493, 2005.
  • [22] G. Celik, H. Akca, and A. Sen, “Investigation of aromotase inhibition by several dietary vegetables in human non-small cell lung cancer cell lines,” Turk. J. Bioch., vol. 38, no. 2, pp. 207–217, 2013.
  • [23] M. Sulak, G. C. Turgut, and A. Sen, “Cerium oxide nanoparticles biosynthesized using fresh green walnut shell in microwave environment and their anticancer effect on breast cancer cells,” Chem. Biodivers., vol. 19, no. 8, p. e202200131, 2022.
  • [24] I. Erdogan Orhan et al., “Evaluation of anti-Alzheimer activity of synthetic coumarins by combination of in vitro and in silico approaches,” Chem. Biodivers., vol. 19, no. 12, p. e202200315, 2022.
  • [25] C. Sahin et al., “New iridium bis-terpyridine complexes: synthesis, characterization, antibiofilm and anticancer potentials,” Biometals, vol. 34, no. 3, pp. 701–713, 2021.
  • [26] E. Yilmaz, M. B. Samur, A. Özcan, E. Ünal, and M. Karakükçü, “Transplantation for ultra high-risk neuroblastoma patients: effect of tandem autologous stem cell transplantation,” J. Health Sci. Med., vol. 4, no. 6, pp. 943–948, 2021.
  • [27] V. Smith and J. Foster, “High-risk neuroblastoma treatment review,” Children (Basel), vol. 5, no. 9, 2018.
  • [28] A. Zafar et al., “Molecular targeting therapies for neuroblastoma: Progress and challenges,” Med. Res. Rev., vol. 41, no. 2, pp. 961–1021, 2021.
  • [29] S. Mallepalli, M. K. Gupta, and R. Vadde, “Neuroblastoma: An updated review on biology and treatment,” Curr. Drug Metab., vol. 20, no. 13, pp. 1014–1022, 2019.
  • [30] N. W. Mabe et al., “Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1,” Nat. Cancer, vol. 3, no. 8, pp. 976–993, 2022.
  • [31] E. Donzelli et al., “Neurotoxicity of platinum compounds: Comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y,” J. Neurooncol., vol. 67, no. 1/2, pp. 65–73, 2004.
  • [32] W. Álvarez-León, I. Mendieta, E. Delgado-González, B. Anguiano, and C. Aceves, “Molecular iodine/cyclophosphamide synergism on chemoresistant neuroblastoma models,” Int. J. Mol. Sci., vol. 22, no. 16, p. 8936, 2021.
  • [33] L.-M. Sun et al., “Nivolumab effectively inhibit platinum-resistant ovarian cancer cells via induction of cell apoptosis and inhibition of ADAM17 expression,” Eur. Rev. Med. Pharmacol. Sci., vol. 21, no. 6, pp. 1198–1205, 2017.
  • [34] M. Wang and A. Yuang-Chi Chang, “Molecular mechanism of action and potential biomarkers of growth inhibition of synergistic combination of afatinib and dasatinib against gefitinib-resistant non-small cell lung cancer cells,” Oncotarget, vol. 9, no. 23, pp. 16533–16546, 2018.
  • [35] Y. Yamamoto et al., “Cetuximab promotes anticancer drug toxicity in rhabdomyosarcomas with EGFR amplification in vitro,” Oncol. Rep., vol. 30, no. 3, pp. 1081–1086, 2013.
  • [36] M. Tesson, G. Anselmi, C. Bell, and R. Mairs, “Cell cycle specific radiosensitisation by the disulfiram and copper complex,” Oncotarget, vol. 8, no. 39, pp. 65900–65916, 2017.
  • [37] M. Hassan, H. Watari, A. AbuAlmaaty, Y. Ohba, and N. Sakuragi, “Apoptosis and molecular targeting therapy in cancer,” Biomed Res. Int., vol. 2014, p. 150845, 2014.
  • [38] K. Million et al., “Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells,” Int. J. Oncol., vol. 29, no. 1, pp. 147–154, 2006.
  • [39] M. Jiang, X. Yi, S. Hsu, C.-Y. Wang, and Z. Dong, “Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity,” Am. J. Physiol. Renal Physiol., vol. 287, no. 6, pp. F1140-7, 2004.
  • [40] R. Hill et al., “Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy,” Cell Death Dis., vol. 4, no. 9, p. e791, 2013.
  • [41] H. Baysal et al., “Cetuximab-induced natural killer cell cytotoxicity in head and neck squamous cell carcinoma cell lines: investigation of the role of cetuximab sensitivity and HPV status,” Br. J. Cancer, vol. 123, no. 5, pp. 752–761, 2020
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Araştırma Makalesi
Yazarlar

Gurbet Çelik Turgut 0000-0002-2306-6972

Erken Görünüm Tarihi 23 Eylül 2023
Yayımlanma Tarihi 28 Eylül 2023
Gönderilme Tarihi 28 Şubat 2023
Kabul Tarihi 15 Ağustos 2023
Yayımlandığı Sayı Yıl 2023

Kaynak Göster

IEEE G. Çelik Turgut, “A Comparative Study of the Antiproliferative and Apoptotic Effects of Some Chemotherapeutic Drugs on Neuroblastoma Cells”, Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, c. 12, sy. 3, ss. 634–641, 2023, doi: 10.17798/bitlisfen.1258011.



Bitlis Eren Üniversitesi
Fen Bilimleri Dergisi Editörlüğü

Bitlis Eren Üniversitesi Lisansüstü Eğitim Enstitüsü        
Beş Minare Mah. Ahmet Eren Bulvarı, Merkez Kampüs, 13000 BİTLİS        
E-posta: fbe@beu.edu.tr