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Investigation of Anti-Tumor Effect in Neuroblastoma Cell Line; Amlodipine & Metformin

Year 2020, Volume 1, Issue 1, 16 - 21, 30.06.2020

Abstract

Background: Neuroblastoma is the most common cranial solid tumor in children. In recent years, scientists have begun to investigate the effect of drugs used to treat other diseases on various types of cancer. Metformin is a popular antihyperglycemic drug. Metformin inhibits glucose uptake by affecting the AMPK metabolism of tumor cells that use glucose for energy. Amlodipine, on the other hand, is a calcium channel blocker and governs Ca2+, which have important role of the cell cycle and metabolism. The purpose of this study; success of amlodipine to increase the effect of metformin against neuroblastoma cell line. Methodology/Main findings: In this study, we prepare the cancer cell line in the proper cell culture medium. Drug doses of metformin (10, 20 and 40 ug), Amlodipine (10 mM), Metformin (10, 20 and 40 ug) + Amlodipine (10 Mm) were administered to NBL cancer cell lines for 24 hours. MTT cell viability test, flow cytometry, total oxidant status, and total antioxidant capacity test were performed 24 hours after the application. Conclusion: The study showed that the combination of high doses of Metformin and amlodipine significantly reduced cell proliferation and antioxidant status compared to control and other groups. Apoptosis levels in combination group are higher than the pure MET and AML groups. When amlodipine was administered alone, there was no antitumor activity in the neuroblastoma cell line, however, metformin was determined to increase antitumor activity.

References

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  • [24] I. Sipahi, S. M. Debanne, D. Y. Rowland, D. I. Simon, and J. C. Fang, "Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials," The lancet oncology, vol. 11, no. 7, pp. 627-636, 2010.
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Year 2020, Volume 1, Issue 1, 16 - 21, 30.06.2020

Abstract

References

  • [1] P. Prša et al., "The potential use of natural products to negate hepatic, renal and neuronal toxicity induced by cancer therapeutics," Biochemical pharmacology, 2019.
  • [2] F. Zi, H. Zi, Y. Li, J. He, Q. Shi, and Z. Cai, "Metformin and cancer: An existing drug for cancer prevention and therapy," Oncology letters, vol. 15, no. 1, pp. 683-690, 2018.
  • [3] A. Aljada and S. A. Mousa, "Metformin and neoplasia: implications and indications," Pharmacology & therapeutics, vol. 133, no. 1, pp. 108-115, 2012.
  • [4] L. M. Ferreira, "Cancer metabolism: the Warburg effect today," Experimental and molecular pathology, vol. 89, no. 3, pp. 372-380, 2010.
  • [5] J.-w. Kim and C. V. Dang, "Cancer's molecular sweet tooth and the Warburg effect," Cancer research, vol. 66, no. 18, pp. 8927-8930, 2006.
  • [6] S. Andrzejewski, S.-P. Gravel, M. Pollak, and J. St-Pierre, "Metformin directly acts on mitochondria to alter cellular bioenergetics," Cancer & metabolism, vol. 2, no. 1, p. 12, 2014.
  • [7] Y. Cheng et al., "For colorectal cancer patients with type II diabetes, could metformin improve the survival rate? A meta-analysis," Clinics and research in hepatology and gastroenterology, 2019.
  • [8] R. Howman-Giles, P. J. Shaw, R. F. Uren, and D. K. Chung, "Neuroblastoma and other neuroendocrine tumors," in Seminars in nuclear medicine, 2007, vol. 37, no. 4: Elsevier, pp. 286-302.
  • [9] N. Ratner, G. M. Brodeur, R. C. Dale, and N. F. Schor, "The “neuro” of neuroblastoma: N euroblastoma as a neurodevelopmental disorder," Annals of neurology, vol. 80, no. 1, pp. 13-23, 2016.
  • [10] I. Lange, J. Koster, and D.-L. T. Koomoa, "Calcium signaling regulates fundamental processes involved in Neuroblastoma progression," Cell calcium, 2019.
  • [11] M. Schwab, F. Westermann, B. Hero, and F. Berthold, "Neuroblastoma: biology and molecular and chromosomal pathology," The lancet oncology, vol. 4, no. 8, pp. 472-480, 2003. [12] G. P. Tonini, "Neuroblastoma by chance," Journal of Cancer, vol. 10, no. 12, p. 2601, 2019.
  • [13] O. E. Kale, O. Awodele, T. F. Ogundare, and M. Ekor, "Amlodipine, an L‐type calcium channel blocker, protects against chlorpromazine‐induced neurobehavioural deficits in mice," Fundamental & clinical pharmacology, vol. 31, no. 3, pp. 329-339, 2017.
  • [14] R. M. La Rovere, G. Roest, G. Bultynck, and J. B. Parys, "Intracellular Ca2+ signaling and Ca2+ microdomains in the control of cell survival, apoptosis and autophagy," Cell calcium, vol. 60, no. 2, pp. 74-87, 2016.
  • [15] J. Yoshida, T. Ishibashi, and M. Nishio, "G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells," Biochemical pharmacology, vol. 73, no. 7, pp. 943-953, 2007.
  • [16] N. C. Colon and D. H. Chung, "Neuroblastoma," Advances in Pediatrics, vol. 58, pp. 297-311, 2011.
  • [17] G. M. Brodeur, "Neuroblastoma: biological insights into a clinical enigma," Nature reviews cancer, vol. 3, no. 3, p. 203, 2003.
  • [18] A. Wynn, A. Vacheron, J. Zuber, and S. S. Solomon, "Metformin Associated With Increased Survival in Type 2 Diabetes Patients With Pancreatic Cancer and Lymphoma," The American journal of the medical sciences, vol. 358, no. 3, pp. 200-203, 2019.
  • [19] S. Thakur, B. Daley, and J. Klubo-Gwiezdzinska, "The role of the antidiabetic drug metformin in the treatment of endocrine tumors," Journal of molecular endocrinology, vol. 1, no. aop, 2019.
  • [20] G. Amable et al., "Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells," The international journal of biochemistry & cell biology, vol. 112, pp. 88-94, 2019.
  • [21] B. K. Das, S. Choukimath, and P. C. Gadad, "Asarone and metformin delays experimentally induced hepatocellular carcinoma in diabetic milieu," Life sciences, vol. 230, pp. 10-18, 2019.
  • [22] T. Binlateh, S. Tanasawet, O. Rattanaporn, W. Sukketsiri, and P. Hutamekalin, "Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells," Evidence-Based Complementary and Alternative Medicine, vol. 2019, 2019.
  • [23] G. Vial, D. Detaille, and B. Guigas, "Role of Mitochondria in the Mechanism (s) of Action of Metformin," Frontiers in endocrinology, vol. 10, p. 294, 2019.
  • [24] I. Sipahi, S. M. Debanne, D. Y. Rowland, D. I. Simon, and J. C. Fang, "Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials," The lancet oncology, vol. 11, no. 7, pp. 627-636, 2010.
  • [25] C. Casalà et al., "The calcium-sensing receptor is silenced by genetic and epigenetic mechanisms in unfavorable neuroblastomas and its reactivation induces ERK1/2-dependent apoptosis," Carcinogenesis, vol. 34, no. 2, pp. 268-276, 2012.
  • [26] P. Pinton, C. Giorgi, R. Siviero, E. Zecchini, and R. Rizzuto, "Calcium and apoptosis: ER-mitochondria Ca 2+ transfer in the control of apoptosis," Oncogene, vol. 27, no. 50, p. 6407, 2008.

Details

Primary Language English
Subjects Biology
Journal Section Research Articles
Authors

Ali TAGHİZADEHGHALEHJOUGHİ This is me
ATATURK UNIVERSITY
0000-0002-3506-0324
Türkiye


Selma SEZEN>
FACULTY OF MEDICINE
0000-0001-6575-6149
Türkiye


Cemil BAYRAM> (Primary Author)
FACULTY OF MEDICINE
0000-0001-8940-8560
Türkiye


Ahmet HACIMÜFTÜOĞLU This is me
FACULTY OF MEDICINE
0000-0002-9658-3313
Türkiye


Medine GÜLLÜCE>
ATATURK UNIVERSITY
0000-0002-5957-8259
Türkiye

Publication Date June 30, 2020
Published in Issue Year 2020, Volume 1, Issue 1

Cite

EndNote %0 Anatolian Journal of Biology Investigation of Anti-Tumor Effect in Neuroblastoma Cell Line; Amlodipine & Metformin %A Ali Taghizadehghalehjoughi , Selma Sezen , Cemil Bayram , Ahmet Hacımüftüoğlu , Medine Güllüce %T Investigation of Anti-Tumor Effect in Neuroblastoma Cell Line; Amlodipine & Metformin %D 2020 %J Anatolian Journal of Biology %P 2687-444X- %V 1 %N 1 %R %U