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

Yıl 2022, Cilt: 5 Sayı: 3, 407 - 423, 15.12.2022

Çağatay Oltulu Melek Akıncı Elvan Bakar

https://doi.org/10.38001/ijlsb.1089164

Öz

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.

Anahtar Kelimeler

Etoposide, galangin, puerarin, neuroblastoma, astrocyte, apoptosis

Destekleyen Kurum

This work was supported by Research Fund of the Trakya University. Project Number: 2018/176.

Proje Numarası

TÜBAP 2018/176.

Kaynakça

• 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.