Antitumor Activity of Etoposide, Puerarin, Galangin and Their Combinations in Neuroblastoma Cells

Antitumor Activity of Etoposide, Puerarin, Galangin and Their Combinations in Neuroblastoma Cells

Neuroblastoma is a disease that is observed in early childhood, originating from the sympathetic nervous system and very difficult to treat. Etoposide, a topoisomerase 2 inhibitor, is one of the agents used in cancer treatment. Galangin and puerarin are plant-based antioxidants with anticancer properties. Since apoptosis induction is one of the methods used in cancer treatment, the evaluation of the mRNA expression levels of apoptosis-related genes is aimed in our study. We investigated the effects of etoposide and galangin/puerarin combination therapy on neuroblastoma and astrocyte cells’ apoptotic process in this study. IC50 dose was determined by MTT test in neuroblastoma and healthy astrocyte lines. Apoptosis-related mRNA gene expressions (topoisomerase 1 and 2α, BAX, p53, TNFα, BCL-2, caspase 3, IL-1, caspase 9) were evaluated in astrocyte and neuroblastoma cells at the dose of neuroblastoma IC50. It was resulted that in all groups, the neuroblastoma IC50 dose was lower than the healthy astrocyte cell IC50 dose and while an increase in apoptotic mRNA expressions was observed in the neuroblastoma cancer line, the mRNA expression changes in the astrocyte cell line did not cause apoptosis. Etoposide combinations antiproliferative effect was decreased relative to etoposide group. It is concluded that single therapy of galangin and puerarin may be promising in the treatment of neuroblastoma.

___

  • 1. Urbani, A., et al., A proteomic investigation into etoposide chemo‐resistance of neuroblastoma cell lines. Proteomics, 2005. 5(3): p. 796-804.
  • 2. Steliarova-Foucher, E., et al., International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol, 2017. 18(6): p. 719-731.
  • 3. Maris, J.M., et al., Neuroblastoma. Lancet, 2007. 369(9579): p. 2106-20.
  • 4. Pinto, N.R., et al., Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J Clin Oncol, 2015. 33(27): p. 3008-17.
  • 5. Berger, S.J., et al., Green tea constituent (--)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells. Biochem Biophys Res Commun., 2001. 288(1): p. 101-5.
  • 6. Nitiss, J.L., Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer, 2009. 9(5): p. 338-50.
  • 7. Karpinich, N.O., et al., The course of etoposide-induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c. J Biol Chem, 2002. 277(19): p. 16547-52.
  • 8. Janicke, R.U., D. Sohn, and K. Schulze-Osthoff, The dark side of a tumor suppressor: anti-apoptotic p53. Cell Death Differ, 2008. 15(6): p. 959-76.
  • 9. Yonish-Rouach, E., The p53 tumour suppressor gene: a mediator of a G1 growth arrest and of apoptosis. Experientia, 1996. 52(10-11): p. 1001-7.
  • 10. Heo, M.Y., S.J. Sohn, and W.W. Au, Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutat Res., 2001. 488(2): p. 135-150.
  • 11. Bacanli, M., A.A. Basaran, and N. Basaran, The antioxidant, cytotoxic, and antigenotoxic effects of galangin, puerarin, and ursolic acid in mammalian cells. Drug Chem Toxicol, 2017. 40(3): p. 256-262.
  • 12. Zhang, H.T., et al., Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol, 2010. 16(27): p. 3377-84.
  • 13. Zeng, H., et al., Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells. Neuroscience, 2015. 294: p. 172-81.
  • 14. Zhang, W., et al., Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK. Cytotechnology, 2013. 65(3): p. 447-55.
  • 15. Zou, W.-W. and S.-P. Xu, Galangin inhibits the cell progression and induces cell apoptosis through activating PTEN and Caspase-3 pathways in retinoblastoma. Biomed Pharmacother., 2018. 97: p. 851-863.
  • 16. Li, J., et al., Anti-colorectal cancer biotargets and biological mechanisms of puerarin: Study of molecular networks. Eur J Pharmacol, 2019. 858: p. 172483.
  • 17. Zhou, Y.X., H. Zhang, and C. Peng, Puerarin: a review of pharmacological effects. Phytother Res, 2014. 28(7): p. 961-75. 18. Berney, D.M., et al., DNA topoisomerase I and II expression in drug resistant germ cell tumours. British Journal of Cancer, 2002. 87(6): p. 624-629.
  • 19. Wen, M., et al., Galangin Induces Autophagy through Upregulation of p53 in HepG2 Cells. Pharmacology, 2012. 89(5-6): p. 247-255.
  • 20. Liu, D., et al., Galangin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Mitochondrial Pathway and Phosphatidylinositol 3-Kinase/Akt Inhibition. Pharmacology, 2018. 102(1-2): p. 58-66.
  • 21. Wang, N., et al., Puerarin protected the brain from cerebral ischemia injury via astrocyte apoptosis inhibition. Neuropharmacology, 2014. 79: p. 282-289.
  • 22. Hu, Y.F., et al., Puerarin inhibits non-small cell lung cancer cell growth via the induction of apoptosis. Oncology Reports, 2018. 39(4): p. 1731-1738.
  • 23. Yu, Z.L. and W.J. Li, Induction of apoptosis by puerarin in colon cancer HT-29 cells. Cancer Letters, 2006. 238(1): p. 53-60.
  • 24. Ye, G.M., et al., Puerarin in inducing apoptosis of bladder cancer cells through inhibiting SIRT1/p53 pathway. Oncology Letters, 2019. 17(1): p. 195-200.
International Journal of Life Sciences and Biotechnology-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2018
  • Yayıncı: International Society of Academicians
Sayıdaki Diğer Makaleler

Evaluation of LC-MS/MS Analysis and In Vitro Biological Activities of Rosa pimpinellifolia Root, Pseudo-fruit, and Seed extracts

Leyla GÜVEN, Ufuk ÖZGEN, Handan SEVİNDİK, İclal AĞAN, Mehmet KOCA, İbrahim TURAN, Selim DEMİR, Yüksel ALİYAZICIOĞLU

SARS-CoV-2 Spike Protein Reseptör Bağlanma Bölgesinde L18F Mutasyonunun Homoloji Modellemesi

Gizem KÖPRÜLÜLÜ KÜÇÜK, Nazlı Irmak GİRİTLİOĞLU

Fritillaria cinsinin ve bu cinsin bir üyesi olan Aygül lalesi’nin (Fritillaria eduardii) dünü, bugünü ve yarını

Daniel KİMSANALİEV, Sevgi MARAKLI, Yilmaz KAYA

YENİLİKÇİ KENDİNDEN İYİLEŞEN HİDROJEL KOMPOZİT OLARAK AZOT KATKILI KARBON KUANTUM DOTS-GELLAN GUM

Serbülent TÜRK, Mahmut ÖZACAR

Characterization of Omega-3 and Omega-6 Fatty Acid Accumulation in Chlorococcum novae-angliae Microalgae Grown under Various Culture Conditions

Elifcan ÇALIŞKAN, Berat Zeki HAZNEDAROĞLU

Diversity Analysis of Common Vetch (Vicia Sativa L.) Lines and Cultivars Using Pairwise Combinations of Universal Rice Primers

Mustafa TOPU, İskender TİRYAKİ

Discrimination of two species (Androctonus crassicauda and Leiurus abdullahbayrami; Buthidae Scorpions) by MALDI-TOF- MS-based PCA

Yasemin NUMANOĞLU ÇEVİK, Mehmet Ali KANAT

Karbon noktaların tarımsal üretimde kullanılması

Mehmet Han BAŞTÜRK, Şahane Funda ARSLANOĞLU, Rumeysa ÖZTÜRK

Assessment of the protective culture potential of the Lactococcus lactis Ganee-5 strain as a preservative against spoilage bacteria in tomato pastes

Abdullahi AJAO, Ganiyat ALASİNRİN

A Current and Common Cause of Secondary Spontaneous Pneumothorax: Covid- 19 Pneumonia

Nurmuhammet TAŞ, Muhammet NALDAN, Fatih ÖNER, Hülya NALDAN, Yener AYDİN