Proliferative effect of the calcium channel blocker Nifedipine on human embryonic kidney cells

Authors

  • Jamil L. Ahmad Department of Pharmacology & Therapeutics, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto State, Nigeria
  • Chukwudi C. Okebaram Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Medicine and Health Sciences, Abia State University, Uturu Nigeria
  • Emmanuel O. Ogbuagu Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Medicine and Health Sciences, Abia State University, Uturu Nigeria
  • Chidozie N. Ogbonnaya Department of Human Anatomy, Faculty of Basic Clinical Sciences, College of Medicine and Health Sciences, Abia State University, Uturu Nigeria
  • Geoffrey C. Asobie Department of Pharmacology and Therapeutics, College of Medicine, Benue State University Makurdi, Benue, Nigeria

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20182669

Keywords:

Antihypertensive agents, Cancer, Growth inhibition, Nifedipine, Polyamines, Proliferation

Abstract

Background: Numerous epidemiological studies have shown a positive as well as negative association between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. The aim was to determine in mechanistic terms the association between the long-term administrations of nifedipineand increased risk of developing cancer with the aid of human embryonic kidney (HEK293) cell line.

Methods: Cell counting using the Trypan blue dye exclusion and 3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine on the growth pattern of HEK293 cells.

Results: Nifedipine had a proliferative effect on HEK293 cells growth and this proliferation is more profound at low concentrations of nifedipine than high concentrations and the proliferation was statistically significant (p<0.01).

Conclusions: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide possible explanation on the link between long term use of nifedipine and development of some human cancers.

References

Volpe M, Azizi M, Danser AH, Nguyen G, Ruilope LM. Twisting arms to angiotensin receptor blockers/antagonists: the turn of cancer. European heart journal. 2015;32(1):19-22.

Paz EA, Garcia-Huidobro J, Ignatenko, NA. Polyamines in cancer. Advances in Clinical Chemistry. 2011;54:45-70.

Wallace HM, Fraser AV, Hughes A. A perspective of polyamine metabolism. The Bioche J. 2003;376(1):1-14.

Verma AK. Polyamines and cancer. In Polyamine Cell Signaling. Humana Press; 2006:313-328.

Tang X, Kim AL, Feith DJ, Pegg AE, Russo J, Zhang H, et al. Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice. The J of Clin Investigat. 2004;113(6):867-75.

Pegg AE, Feith DJ, Fong LY, Coleman CS, O'Brien TG, Shantz LM. Transgenic mouse models for studies of the role of polyamines in normal, hypertrophic and neoplastic growth. Biochemical Society transactions. 2003;31(2):356-60.

Coleman CS, Pegg AE, Megosh LC, Guo Y, Sawicki JA, O'Brien TG. Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis. Carcinogenesis. 2002;23(2):359-64.

Fujii A, Matsumoto H, Nakao S, Teshigawara H, Akimoto Y. Effect of calcium-channel blockers on cell proliferation, DNA synthesis and collagen synthesis of cultured gingival fibroblasts derived from human nifedipine responders and non-responders. Archives of Oral Biology. 1994;39(2):99-104.

Li CI, Daling JR, Tang MC, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA internal medicine. 2013;173(17):1629-37.

Mason RP. Calcium channel blockers, apoptosis and cancer: is there a biologic relationship? J of the Ame Col of Cardiol. 1999;34(7):1857-66.

Kondo S, Yin D, Morimura T, Takeuchi J. Combination therapy with cisplatin and nifedipine inducing apoptosis in multidrug-resistant human glioblastoma cells. J of Neurosu. 1995;82(3)469-74.

Conrad DM, Furlong SJ, Doucette CD, West KA, Hoskin DW. The Ca2 channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells. Apoptosis. 2010;15(5):597-607.

Grimaldi-Bensouda L, Klungel O, Kurz X, DE Groot MC, Afonso ASM, DE Bruin, et al. Calcium channel blockers and cancer: a risk analysis using the UK Clinical Practice Research Datalink (CPRD). BMJ open. 2016;6(1):009147.

Stepanenko A, Dmitrenko V. HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene. 2015;569(2):182-90.

Takeuchi R, Matsumoto H, Okada H, Hori M, Gunji A, Hakozaki K, et al. Differences of cell growth and cell cycle regulators induced by basic fibroblast growth factor between nifedipine responders and non-responders. J of Pharmaco Sci. 2007;103(2):168-74.

Soto-Pantoja DR, Menon J, Gallagher PE, Tallant EA. Angiotensin-(1-7) inhibits tumor angiogenesis in human lung cancer xenografts with a reduction in vascular endothelial growth factor. Molecular cancer therapeutics. 2009;8(6):1676-83.

Pahor M, Guralnik JM, Salive ME, Corti MC, Carbonin P, Havlik RJ. Do calcium channel blockers increase the risk of cancer? Ame J of Hyperten. 1996;9(7):695-9.

Leung HW, Hung L, Chan AL, Mou C. Long-term use of antihypertensive agents and risk of breast cancer: a population-based case-control study. Cardiology and therapy. 2015;4(1):65-76.

Bose T, Cieślar-Pobuda A, Wiechec E. Role of ion channels in regulating Ca2 and plus; homeostasis during the interplay between immune and cancer cells. Cell death and disease. 2015;6(2):1648.

Auvinen M, Paasinen A, Andersson LC, Holtta E. Ornithine decarboxylase activity is critical for cell transformation. Nature. 1992;360(6402):355-8.

Holtta E, Auvinen M, Andersson LC. Polyamines are essential for cell transformation by pp60v-src: delineation of molecular events relevant for the transformed phenotype. The J of Cell Bio. 1993;122(4):903-14.

Wallace HM, Duthie J, Evans DM, Lamond S, Nicoll KM, Heys SD. Alterations in polyamine catabolic enzymes in human breast cancer tissue. Clinical cancer research: an official journal of the American Association for Cancer Research. 2000;6(9):3657-61.

Gerner EW, Meyskens FL. Polyamines and cancer: old molecules, new understanding. Nature Reviews Cancer. 2004;4(10):781-92.

Bachrach U. Polyamines and cancer: mini review article. Amino acids. 2004;26(4):307-9.

Wallace HM, Niiranen K. Polyamine analogues–an update. Amino acids. 2007;33(2):261-5.

Downloads

Published

2018-06-22

How to Cite

Ahmad, J. L., Okebaram, C. C., Ogbuagu, E. O., Ogbonnaya, C. N., & Asobie, G. C. (2018). Proliferative effect of the calcium channel blocker Nifedipine on human embryonic kidney cells. International Journal of Basic & Clinical Pharmacology, 7(7), 1226–1231. https://doi.org/10.18203/2319-2003.ijbcp20182669

Issue

Section

Original Research Articles