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IJSTR >> Volume 5 - Issue 12, December 2016 Edition

International Journal of Scientific & Technology Research  
International Journal of Scientific & Technology Research

Website: http://www.ijstr.org

ISSN 2277-8616

Cytotoxic Effect Of Verapamil On Human Embryonic Kidney Cell Line

[Full Text]



Jamil L Ahmad, Chukwudi C Okebaram, Abdullahi Samaila



Anti-hypertensives, cancer, growth inhibition, proliferative, verapamil



Introduction: The link between long term use of verapamil and cancer development has been suggested in literature many years back. However, there are numerous controversies surrounding this association with several epidemiological studies in the positive, negative and non-association between verapamil and cancer development. Aim: To investigate in mechanistic terms the link between chronic use of a calcium channel blocker (verapamil) and cancer development using human embryonic kidney (HEK293) cell line. Method: Trypan blue dye exclusion (cell counting) and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to determine the proliferative as well as cytotoxic effects of verapamil. Results: Verapamil had a growth inhibitory rather than proliferative effect on HEK293 cells and the growth inhibition was found to be significant (p<0.05). Conclusion: The long term use of verapamil is associated with cellular growth inhibition and this possibly explained the rationale behind its use as part of combination chemotherapy for some human cancers.



[1] BAO, L., HAQUE, A., JACKSON, K., HAZARI, S., MOROZ, K., JETLY, R. and DASH, S., 2011. Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model. The American journal of pathology, 178(2), pp. 838-852.

[2] BERRIDGE, M.J., LIPP, P. and BOOTMAN, M.D., 2000. The versatility and universality of calcium signalling. Nature reviews Molecular cell biology, 1(1), pp. 11-21.

[3] BOSE, T., CIEŚLAR-POBUDA, A. and WIECHEC, E., 2015. Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells. Cell death & disease, 6(2), pp. e1648.

[4] CONRAD, D.M., FURLONG, S.J., DOUCETTE, C.D., WEST, K.A. and HOSKIN, D.W., 2010. The Ca2 channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells. Apoptosis, 15(5), pp. 597-607.

[5] DZIEGIELEWSKA, B., GRAY, L.S. and DZIEGIELEWSKI, J., 2014. T-type calcium channels blockers as new tools in cancer therapies. Pflügers Archiv-European Journal of Physiology, 466(4), pp. 801-810.

[6] ELLIOTT, W.J. and RAM, C.V.S., 2011. Calcium channel blockers. The Journal of Clinical Hypertension, 13(9), pp. 687-689.

[7] FUJII, A., MATSUMOTO, H., NAKAO, S., TESHIGAWARA, H. and AKIMOTO, Y., 1994. 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, 39(2), pp. 99-104.

[8] GRIMALDI-BENSOUDA, L., KLUNGEL, O., KURZ, X., DE GROOT, M.C., AFONSO, A.S.M., DE BRUIN, M.L., REYNOLDS, R. and ROSSIGNOL, M., 2016. Calcium channel blockers and cancer: a risk analysis using the UK Clinical Practice Research Datalink (CPRD). BMJ open, 6(1), pp. e009147.

[9] GUPTA, V., KAMATH, N., TKALCEVIC, G.T. and SINGH, S.V., 1994. Potentiation of tamoxifen activity by verapamil in a human breast cancer cell line. Biochemical pharmacology, 47(9), pp. 1701-1704.

[10] HAJIGHASEMI, F. and KAKADEZFULI, N., 2012. Sensitivity of monocytic cell lines to verapamil in vitro. Research Journal of Biological Sciences, 7(5), pp. 209-214.

[11] JANG, S.J., CHOI, H.W., CHOI, D.L., CHO, S., RIM, H., CHOI, H., KIM, K., HUANG, M., RHIM, H. and LEE, K., 2013. In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers. Bioorganic & medicinal chemistry letters, 23(24), pp. 6656-6662.

[12] KHWAJA, A., 2010. PI3K as a target for therapy in haematological malignancies. Phosphoinositide 3-kinase in Health and Disease. Springer, pp. 169-188.

[13] LI, C.I., DALING, J.R., TANG, M.C., HAUGEN, K.L., PORTER, P.L. and MALONE, K.E., 2013. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA internal medicine, 173(17), pp. 1629-1637.

[14] MASON, R.P., 1999. Calcium channel blockers, apoptosis and cancer: is there a biologic relationship? Journal of the American College of Cardiology, 34(7), pp. 1857-1866.

[15] MCTAVISH, D. and SORKIN, E.M., 1989. Verapamil. Drugs, 38(1), pp. 19-76.

[16] MEISTER, S., FREY, B., LANG, V.R., GAIPL, U.S., SCHETT, G., SCHLÖTZER-SCHREHARDT, U. and VOLL, R.E., 2010. Calcium Channel Blocker Verapamil Enhances Reticulum Stress and Death Induced by Proteasome Inhibition in Myeloma Cells. Neoplasia, 12(7), pp. 550-IN3.

[17] OPIE, L., 1997. Pharmacological differences between calcium antagonists. European heart journal, 18 (suppl A), pp. 71-79.

[18] PEREZ-REYES, E., 2003. Molecular physiology of low-voltage-activated t-type calcium channels. Physiological Reviews, 83(1), pp. 117-161.

[19] RANG, H.P., RITTER, J.M., FLOWER, R.J. and HENDERSON, G., 2014. Rang & Dale's Pharmacology: with STUDENT CONSULT Online Access. Elsevier Health Sciences.

[20] STEPANENKO, A. and DMITRENKO, V., 2015. HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene, 569(2), pp. 182-190.

[21] TAIRA, N., 1987. Differences in cardiovascular profile among calcium antagonists. The American Journal of Cardiology, 59(3), pp. B24-B29.

[22] VOLPE, M., AZIZI, M., DANSER, A.H., NGUYEN, G. and RUILOPE, L.M., 2011. Twisting arms to angiotensin receptor blockers/antagonists: the turn of cancer. European heart journal, 32(1), pp. 19-22.