Advertisement

Molecular Biology Reports

, Volume 46, Issue 2, pp 2523–2528 | Cite as

Vincristine combination with Ca+2 channel blocker increase antitumor effects

  • Ali Taghizadehghalehjoughi
  • Selma SezenEmail author
  • Ahmet Hacimuftuoglu
  • Medine Güllüce
Original Article
  • 94 Downloads

Abstract

In this study, it was aimed to determine the effects of Amlodipine, a calcium channel blocker and vincristine (VCR) an antineoplastic, on human neuroblastomas using different doses. The cytotoxicity assays of the study were performed using the MTT method depending on time and concentration. After obtaining the mixture (up to 85% for SH-SY5Y) and sufficient branches (cortex neurons), the cells were treated with amlodipine (10 µM) and vincristine (0.5, 1 and 2 µg) at different concentrations for 24 h. MTT assay was performed by the commercially available kit (Sigma Aldrich, USA). Cells were harvested, washed and stained with PI and Annexin V, respectively, according to the manufacturer’s protocol (Biovision, USA). Than analyzes were carried out. The results were quite impressive. When amlodipine (10 µM) was administered alone there was little change compared to the control. However, all doses of amlodipine (10 µM) and vincristine (0.5, 1 and 2 µg) were greater than the deaths in the doses alone (0.5, 1 and 2 µg) of vincristine alone. (P < 0.05). As a result, the combination of vincristine and amlodipine is more effective than vincristine alone in reducing the viability of cancer cells.

Keywords

Neuroblastoma Calcium channel blockers Amlodipine Vincristine 

Notes

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

References

  1. 1.
    Zhang Y et al (2011) Targeting therapy with mitosomal daunorubicin plus amlodipine has the potential to circumvent intrinsic resistant breast cancer. Mol Pharm 8(1):162–175CrossRefGoogle Scholar
  2. 2.
    Aksoy Y (2010) Ways for overcoming drug resistance in cancer: designing new drugs: invited commentary. Turkiye Klinikleri Tip Bilimleri Dergisi 30(6):2011–2016Google Scholar
  3. 3.
    Milan A et al (2014) Arterial hypertension and cancer. Int J Cancer 134(10):2269–2277CrossRefGoogle Scholar
  4. 4.
    Yesilyurt F, Taghizadehghalehjoughi A, Hacimuftuoglu A (2018) ACTH and amlodipine effects on neuroblastoma and cortical neurons. Neuroendocrinology 107:19–19Google Scholar
  5. 5.
    Dolphin AC (2018) Voltage-gated calcium channels: their discovery, function and importance as drug targets. Brain Neurosci Adv.  https://doi.org/10.1177/2398212818794805 Google Scholar
  6. 6.
    Sipahi I et al (2010) Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol 11(7):627–636CrossRefGoogle Scholar
  7. 7.
    Carvalho LF, Silva AMF, Carvalho AA (2017) The use of antioxidant agents for chemotherapy-induced peripheral neuropathy treatment in animal models. Clin Exp Pharmacol Physiol 44(10):971–979CrossRefGoogle Scholar
  8. 8.
    kars Demirel M (2008) Molecular mechanisms of vincristine and paclitaxel resistance in mcf-7 cell line. Middle East Technical University, AnkaraGoogle Scholar
  9. 9.
    Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108(2):153–164CrossRefGoogle Scholar
  10. 10.
    Gregorio A et al (2008) Small round blue cell tumours: diagnostic and prognostic usefulness of the expression of B7-H3 surface molecule. Histopathology 53(1):73–80CrossRefGoogle Scholar
  11. 11.
    Pizzo PA, Poplack DG (2015) Principles and practice of pediatric oncology. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  12. 12.
    Ratner N et al. (2016) The “neuro” of neuroblastoma: neuroblastoma as a neurodevelopmental disorder. Ann Neurol 80(1):13–23CrossRefGoogle Scholar
  13. 13.
    Erbayraktar Z et al (2012) The role of p14ARF methylation in neuroblastoma minimal residual disease. Turkish J Biochem Turk Biyokimya Dergisi 37(2):129–138CrossRefGoogle Scholar
  14. 14.
    Zamponi GW et al (2015) The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev 67(4):821–870CrossRefGoogle Scholar
  15. 15.
    Abernethy DR, Schwartz JB (1999) Calcium-antagonist drugs. N Engl J Med 341(19):1447–1457.  https://doi.org/10.1056/NEJM199911043411907 CrossRefGoogle Scholar
  16. 16.
    Kim MS et al (2003) Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Can Res 63(21):7291–7300Google Scholar
  17. 17.
    Groh T et al (2012) Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells. Neuroendocrinol Lett 33:16–24Google Scholar
  18. 18.
    Groh T et al (2015) The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. Int J Oncol 47(1):343–352CrossRefGoogle Scholar
  19. 19.
    Emin NM, Taghizadehghalehjoughi A (2019) Should we use remifentanil in every dose and every case? J Clin Anal Med 10(1):21–25CrossRefGoogle Scholar
  20. 20.
    Cozzi DA et al (2013) Long-term follow-up of the “wait and see” approach to localized perinatal adrenal neuroblastoma. World J Surg 37(2):459–465.  https://doi.org/10.1007/s00268-012-1837-0 CrossRefGoogle Scholar
  21. 21.
    Fleckenstein A et al (1969) A new group of competitive Ca antagonists with highly potent inhibitory effects on excitation-contraction coupling in mammalian myocardium. Pflugers Arch Eur J Physiol 307:R25Google Scholar
  22. 22.
    Khokhani RC et al (1993) Amlodipine in mild and moderate hypertension: initial Indian experience. J Assoc Physicians India 41(10):662–663Google Scholar
  23. 23.
    Pahor M et al (1996) Trends of the characteristics and appropriateness of admissions to acute geriatric and medical wards in Italy from 1988 through 1993. Gruppo Italiano di Farmacovigilanza nell’Anziano–GIFA. Eur J Epidemiol 12(6):563–571CrossRefGoogle Scholar
  24. 24.
    Bangalore S et al (2011) Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol 12(1):65–82CrossRefGoogle Scholar
  25. 25.
    Nissen SE (2010) Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol 11(7):605–606CrossRefGoogle Scholar
  26. 26.
    Mickisch GH et al (1990) Effects of calcium antagonists in multidrug resistant primary human renal cell carcinomas. Cancer Res 50(12):3670–3674Google Scholar
  27. 27.
    Sezzi ML et al (1985) Effects of a calcium-antagonist (flunarizine) on cancer cell movement and phagocytosis. Anticancer Res 5(3):265–271Google Scholar
  28. 28.
    Ghosh S, Sircar M (2008) Calcium channel blocker overdose: experience with amlodipine. Indian J Crit Care Med 12(4):190–193CrossRefGoogle Scholar
  29. 29.
    Sim MT, Stevenson FT (2008) A fatal case of iatrogenic hypercalcemia after calcium channel blocker overdose. J Med Toxicol 4(1):25–29CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, Faculty of Veterinary MedicineErzurumTurkey
  2. 2.Department of Medical PharmacologyAtatürk UniveristyErzurumTurkey
  3. 3.Department of Biology, Faculty of ScienceAtaturk UniversityErzurumTurkey

Personalised recommendations