Ali TAGHİZADEHGHALEHJOUGHİ, Ahmet HACİMUFTUOGLU, Aysegul YİLMAZ

Na+ channel blocker enhances metformin effects on neuroblastoma cell line

The aim of the current study is the evaluation of valproic acid and Metformin antitumor effect on neuroblastoma (SH-SY5Y) and answer the question, is valproic acid (VPA) increase Metformin (MET) antitumor effect on the SH-SY5Y cancer cell line or not. The SH-SY5Y cell line was grown in culture medium. A different dose of MET and VPA were applied to SH-SY5Y cancer cell lines for 24 hrs. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability, Annexin-V-FITC apoptosis, Total Antioxidant Capacity (TAC) and Total Oxidant Status (TOS) tests were done 24 hours after drug administration. As a result of the tests, the combination of MET and VPA reduced cancer cell viability compared with the control group (p

PDF

___

1. Davidoff, AM. Neuroblastoma. Semin Pediatr Surg, 2012;21:2-14.

2. Young JL Jr, Ries LG, Silverberg E, et al. Cancer incidence, survival, and mortality for children younger than age 15 years. Cancer. 1986;58:598-602.

3. Kumar A, Al-Sammarraie N, DiPette DJ, et al. Metformin impairs Rho GTPase signaling to induce apoptosis in neuroblastoma cells and inhibits growth of tumors in the xenograft mouse model of neuroblastoma. Oncotarget, 2014;5:11709-22.

4. Shabbeer S, Kortenhorst MS, Kachhap S, et al. Multiple Molecular pathways explain the anti-proliferative effect of valproic acid on prostate cancer cells in vitro and in vivo. Prostate. 2007;67:1099-10.

5. Xia Q, Sung J, Chowdhury W, et al. Chronic administration of valproic acid inhibits prostate cancer cell growth in vitro and in vivo. Cancer Res. 2006:66:7237-44.

6. Sidana A, Wang M, Chowdhury WH, et al. Does valproic acid induce neuroendocrine differentiation in prostate cancer? J Biomed Biotechnol. 2011;2011:607480.

7. Farber NB, Jiang XP, Heinkel C, et al. Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity. Mol Psychiatry, 2002;7:726-33.

8. Kang H, Gillespie TW, Goodman M, et al. Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer. Cancer, 2014;120:1394-400.

9. Sidana A, Wang M, Shabbeer S, et al., Mechanism of growth inhibition of prostate cancer xenografts by valproic acid. J Biomed Biotechnol, 2012;2012:180363.

10. Chavez-Blanco A, Perez-Plasencia C, Perez-Cardenas E, et al. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines. Cancer Cell Int, 2006;6:2.

11. Kim MS, Blake M, Baek JH, et al., Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 2003;63:7291-300.

12. Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, et al, Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9:1092-9.

13. Evans JM, Le Marchand-Brustel Y, Tanti JF, et al, Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304-5.

14. Zhang ZJ, Bi Y, Li S, et al, Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and meta-analysis. Am J Epidemiol, 2014;180:11-4.

15. Lau YK, Du X, Rayannavar V, et al. Metformin and erlotinib synergize to inhibit basal breast cancer. Oncotarget. 2014;5:10503-17.

16. Zhang Q, Kong J, Dong S, et al. Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation. Cancer Cell Int. 2017;17:48.

17. Hanna RK, Zhou C, Malloy KM, et al., Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Gynecol Oncol. 2012;125:458-69.

18. Sinnett-Smith J, Kisfalvi K, Kui R, et al. Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in pancreatic cancer cells: dependence on glucose concentration and role of AMPK. Biochem Biophys Res Commun. 2013;430:352-7.

19. Taghizadehghalehjoughi A, Hacimuftuoglu A, Cetin M, et al. Effect of metformin/irinotecan-loaded poly-lactic-co-glycolic acid nanoparticles on glioblastoma: in vitro and in vivo studies. Nanomedicine (Lond). 2018;13:1595-606.

20. Kamalak H, Kamalak A, Taghizadehghalehjoughi A et al. Cytotoxic and biological effects of bulk fill composites on rat cortical neuron cells. Odontology. 2018;106:377-88.

21. Kamalak HA, Kamalak A, Taghizadehghalehjoughi A, Cytotoxic effects of new-generation bulk-fill composites on human dental pulp stem cells. Cell Mol Biol (Noisy-le-grand). 2018;64:62-71.

22. Ahiskalioglu A, Ince I, Aksoy M, et al. Comparative investigation of protective effects of metyrosine and metoprolol against ketamine cardiotoxicity in Rats. Cardiovasc Toxicol. 2015;15:336-44.

23. Costa D, Gigoni A, Würth R, et al. Metformin inhibition of neuroblastoma cell proliferation is differently modulated by cell differentiation induced by retinoic acid or overexpression of NDM29 non-coding RNA. Cancer Cell Int. 2014;14:59.

24. Takahashi A, Kimura F, Yamanaka A, et al. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell Int. 2014;14:53.

25. Weichert W, Röske A, Gekeler V, et al. Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Br J Cancer. 2008;98:604-10.

26. Shan Z, Feng-Nian R, Jie G, et al. Effects of valproic acid on proliferation, apoptosis, angiogenesis and metastasis of ovarian cancer in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13:3977-82.