Sains Malaysiana 49(4)(2020): 839-846

http://dx.doi.org/10.17576/jsm-2020-4904-13

Potential Association of Nicotinamide on the Telomerase Activity and Telomere Length Mediated by PARP-1 Mechanism in Myeloid Cancer

(Potensi Perkaitan Nikotinamida ke atas Aktiviti Telomerase dan Panjang Telomer Disebabkan oleh Mekanisme PARP-1 pada Kanser Mieloid)

NUR RASYIDAH MUHAMMAD¹, AZLINA AHMAD², SITI NORASIKIN MOHD NAFI³, FARIZAN AHMAD⁴, ZARIYANTEY ABDUL HAMID⁵ & SARINA SULONG^1*

¹Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kelantan Darul Naim, Malaysia

²School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kelantan Darul Naim, Malaysia

³Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kelantan Darul Naim, Malaysia

⁴Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kelantan Darul Naim, Malaysia

⁵School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 21 April 2019/Diterima: 7 Januari 2020

ABSTRACT

Administration of nicotinamide is affecting various types of cells through its survival, maturation, and differentiation. Nicotinamide as part of vitamin B₃, plays an important role in DNA repair and maintenance of the genomic stability which related to its function as a NAD⁺ precursor that involve in many biological processes. During DNA breaks, PARP-1 mechanism will be activated and use NAD⁺ as a substrate in process of DNA damage and repair that will result to either cell repair and cell death. In the meantime, in presence of nicotinamide that is also acting as a PARP-1 inhibitor, causing inability of the repair mechanism to fix the entire DNA damage which also lead to the cell death. Therefore, loss of PARP-1 enzyme will cause disturbance in the DNA repair process. Telomere shortening rate was reduced in the presence of nicotinamide that might related with telomerase enzyme which able to maintain the telomere length of the cell. Other than that, telomere also can be influenced by PARP-1 activity where it might show some correlation between nicotinamide, telomere and telomerase that could related with PARP-1 mechanism. Currently, there is no treatment options that respond effectively in chronic myeloid leukemia (CML) in blast crisis (BC) phase without any side effect and it is require an identification of new drug therapies to treat the CML patients. By understanding the role and potential of nicotinamide relation with PARP-1 mechanism in telomere and telomerase status may improve the therapeutic strategy for chronic myeloid leukemia.

Keywords: Nicotinamide; PARP-1; telomerase; telomere

Abstrak

Pengambilan nikotinamida menjejaskan pelbagai jenis sel melalui kelangsungan hidup, kematangan dan pembezaannya. Nikotinamida sebagai sebahagian daripada vitamin B₃ memainkan peranan penting dalam pembaikan dan penyelenggaraan kestabilan genom DNA yang berkaitan dengan fungsinya sebagai prakursor NAD⁺ yang melibatkan banyak proses biologi. Semasa DNA pecah, mekanisme PARP-1 akan diaktifkan dan menggunakan NAD⁺ sebagai substrat dalam proses kerosakan dan pembaikan DNA yang akan menyebabkan pembaikan sel dan kematian sel. Sementara itu, dengan adanya nikotinamida yang juga bertindak sebagai perencat PARP-1, menyebabkan ketidakupayaan mekanisme pembaikan untuk memperbaiki keseluruhan kerosakan DNA yang juga membawa kepada kematian sel. Oleh itu, kehilangan enzim PARP-1 akan menyebabkan gangguan dalam proses pembaikan DNA. Kadar pemendekan telomer berkurang dengan kehadiran nikotinamida yang mungkin berkaitan dengan enzim telomerase yang dapat mengekalkan panjang telomer sel. Selain itu, telomer juga boleh dipengaruhi oleh aktiviti PARP-1 dan ia mungkin menunjukkan beberapa korelasi antara nikotinamida, telomer dan telomerase yang boleh dikaitkan dengan mekanisme PARP-1. Pada masa ini, tiada pilihan rawatan yang bertindak balas dengan berkesan dalam leukemia mieloid kronik (CML) dalam fasa krisis blas (BC) tanpa sebarang kesan sampingan dan memerlukan pengenalan terapi ubat baru untuk merawat pesakit CML. Dengan memahami peranan dan potensi hubungan nikotinamida dengan mekanisme PARP-1 dalam telomer dan status telomerase dapat meningkatkan strategi terapeutik untuk leukemia mieloid kronik.

Kata kunci: Nikotinamida; PARP-1; telomerase; telomer

RUJUKAN

Allende-Castro, C., Espina-Marchant, P., Bustamante, D., Rojas-Mancilla, E., Neira, T., Gutierrez-Hernandez, M., Esmar, D., Valdes, J.L., Morales, P., Gebicke-Haerter, P.J. & Herrera-Marschitz, M. 2012. Further studies on the hypothesis of PARP-1 inhibition as a strategy for lessening the long-term effects produced by perinatal asphyxia: Effects of nicotinamide and theophylline on PARP-1 activity in brain and peripheral tissue. Neurotoxicity Research 22(1): 79-90.

Audrito, V., Vaisitti, T., Rossi, D., Gottardi, D., D'Arena, G., Laurenti, L., Gaidano, G., Malavasi, F. & Deaglio, S. 2011. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network. Cancer Research 71(13): 4473-4483.

Belenky, P., Bogan, K.L. & Brenner, C. 2007. NAD+ metabolism in health and disease. Trends in Biochemical Sciences 32(1): 12-19.

Boesten, D.M.P.H.J., de Vos-Houben, J.M.J., Timmermans, L., den Hartog, G.J., Bast, A. & Hageman, G.J. 2013. Accelerated aging during chronic oxidative stress: A role for PARP-1. Oxidative Medicine and Cellular Longevity 2013: 680414.

Bogan, K.L. & Brenner, C. 2008. Nicotinic acid, nicotinamide, and nicotinamide riboside: A molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr. 28: 115-130.

Bouffler, S.D., Morgan, W.F., Pandita, T.K. & Slijepcevic, P. 1996. The involvement of telomeric sequences in chromosomal aberrations. Mutation Research/Reviews in Genetic Toxicology 366(2): 129-135.

Burkle, A. 2001. Physiology and pathophysiology of poly (ADP‐ribosyl)ation. Bioessays 23(9): 795-806.

Cao, Y., Bryan, T.M. & Reddel, R.R. 2008. Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells. Cancer Science 99(6): 1092-1099.

Chen, A.C., Martin, A.J., Choy, B., Fernández-Peñas, P., Dalziell, R.A., McKenzie, C.A., Scolyer, R.A., Dhillon, H.M., Vardy, J.L., Kricker, A., St. George, G., Chinniah, N., Halliday, G.M. & Damian, D.L. 2015. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. New England Journal of Medicine 373(17): 1618-1626.

De Lorenzo, S., Patel, A., Hurley, R. & Kaufmann, S.H. 2013. The elephant and the blind men: Making sense of PARP inhibitors in homologous recombination deficient tumor cells. Frontiers in Oncology 3: 228.

De Soto, J.A., Wang, X., Tominaga, Y., Wang, R.H., Cao, L., Qiao, W., Cuiling, Li., Xu, X.L., Skoumbourdis, A.P., Prindiville, S.A., Thomas, C.J. & Deng, C-X. 2006. The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors. International Journal of Biological Sciences 2(4): 179-185.

Druker, B.J. 2008. Translation of the Philadelphia chromosome into therapy for CML. Blood 112(13): 4808-4817.

Druker, B.J., Talpaz, M., Resta, D.J., Peng, B., Buchdunger, E., Ford, J.M., Lydon, N.B., Kantarjian, H., Capdeville, R., Ohno-Jones, S. & Sawyers, C.L. 2001. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New England Journal of Medicine 344(14): 1031-1037.

Druker, B.J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G.M., Fanning, S., Zimmermann, J. & Lydon, N.B. 1996. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nature Medicine 2(5): 561-566.

Hazlehurst, L.A., Bewry, N.N., Nair, R.R. & Pinilla-Ibarz, J. 2009. Signaling networks associated with BCR–ABL–dependent transformation. Cancer Control 16(2): 100-107.

Holl, V., Coelho, D., Weltin, D., Hyun, J., Dufour, P. & Bischoff, P. 2000. Modulation of the antiproliferative activity of anticancer drugs in hematopoietic tumor cell lines by the poly (ADP-ribose) polymerase inhibitor 6 (5H)-phenanthridinone. Anticancer Research 20(5A): 3233-3241.

Horikawa, I. & Barrett, J.C. 2003. Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms. Carcinogenesis 24(7): 1167-1176.

Hughes, T. & White, D. 2013. Which TKI? An embarrassment of riches for chronic myeloid leukemia patients. ASH Education Program Book 2013 1: 168-175.

Ida, C., Ogata, S., Okumura, K. & Taguchi, H. 2009. Induction of differentiation in k562 cell line by nicotinic acid-related compounds. Bioscience, Biotechnology, and Biochemistry 73(1): 79-84.

Jacob, R.A. & Swendseid, M. 1996. Niacin. Present Knowledge in Nutrition 7: 185-190.

Jacobson, E.L., Shieh, W.M. & Huang, A.C. 1999. Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis. In ADP-Ribosylation Reactions: From Bacterial Pathogenesis to Cancer, edited by Alvarez-Gonzalez R. Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease Vol. 30.  Boston: Springer. pp. 69-74.

Jin, J., Lee, K.B., Park, S.Y. & Jang, J.J. 2011. Nicotinamide inhibits hepatic fibrosis by suppressing DNA synthesis and enhancing apoptosis of hepatic stellate cells. Virchows Archive 458(6): 689.

Kang, H.T., Lee, H.I. & Hwang, E.S. 2006. Nicotinamide extends replicative lifespan of human cells. Aging Cell 5(5): 423-436.

Kantarjian, H., Sawyers, C., Hochhaus, A., Guilhot, F., Schiffer, C., Gambacorti-Passerini, C., Niederwieser, D., Resta, D., Capdeville, R., Zoellner, U., Talpaz, M. & Druker, B. 2002. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. New England Journal of Medicine 346(9): 645-652.

Karthikeyan, K. & Thappa, D.M. 2002. Pellagra and skin. International Journal of Dermatology 41(8): 476-481.

Kauppinen, T.M., Gan, L. & Swanson, R.A. 2013. Poly (ADP-ribose) polymerase-1-induced NAD+ depletion promotes nuclear factor-κB transcriptional activity by preventing p65 de-acetylation. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1833(8): 1985-1991.

Kjellen, E., Jonsson, G.G., Pero, R.W. & Christensson, P.I. 1985. Effects of hyperthermia and nicotinamide on DNA repair synthesis, ADP-ribosyl transferase activity, NAD+ and ATP pools, and cytotoxicity in γ-irradiated human mononuclear leukocytes. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine 49(1): 151-162.

Knip, M., Douek, I.F., Moore, W.P.T., Gillmor, H.A., McLean, A.E.M., Bingley, P.J., Gale, E.A. & European Nicotinamide Diabetes Intervention Trial Group. 2000. Safety of high-dose nicotinamide: A review. Diabetologia 43(11): 1337-1345.

Lee, H.I., Jang, S.Y., Kang, H.T. & Hwang, E.S. 2008. p53-, SIRT1-, and PARP-1-independent downregulation of p21WAF1 expression in nicotinamide-treated cells. Biochemical and Biophysical Research Communications 368(2): 298-304.

Leitner, A.A., Hochhaus, A. & Muller, M.C. 2011. Current treatment concepts of CML. Current Cancer Drug Targets 11(1): 31-43.

Litwack, G. 2018. Vitamins and nutrition. In Human Biochemistry, edited by  G. Litwack. New York: Academic Press. pp. 645-680.

Liu, S.K., Coackley, C., Krause, M., Jalali, F., Chan, N. & Bristow, R.G. 2008. A novel poly (ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia. Radiotherapy and Oncology 88(2): 258-268.

Lozzio, C.B. & Lozzio, B.B. 1975. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45(3): 321-334.

Magan, N., Isaacs, R.J. & Stowell, K.M. 2012. Treatment with the PARP-inhibitor PJ34 causes enhanced doxorubicin-mediated cell death in HeLa cells. Anti-Cancer Drugs 23(6): 627-637.

Malyuchenko, N., Kotova, E.Y., Kulaeva, O., Kirpichnikov, M. & Studitskiy, V. 2015. PARP1 Inhibitors: Antitumor drug design. Acta Naturae (англоязычная версия) 7(3): 26.

Mason, K.A., Valdecanas, D., Hunter, N.R. & Milas, L. 2008. INO-1001, a novel inhibitor of poly (ADP-ribose) polymerase, enhances tumor response to doxorubicin. Investigational New Drugs 26(1): 1-5.

Matsubara, Y., Murata, M., Yoshida, T., Watanabe, K., Saito, I., Miyaki, K., Kazuyuki, O. & Ikeda, Y. 2006. Telomere length of normal leukocytes is affected by a functional polymorphism of hTERT. Biochemical and Biophysical Research Communications 341(1): 128-131.

Melo, J.V. & Barnes, D.J. 2007. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nature Reviews Cancer 7(6): 441-453.

Opitz, O.G. 2005. Telomeres, telomerase and malignant transformation. Current Molecular Medicine 5(2): 219-226.

Park, J., Halliday, G.M., Surjana, D. & Damian, D.L. 2010. Nicotinamide prevents ultraviolet radiation‐induced cellular energy loss. Photochemistry and Photobiology 86(4): 942-948.

Paul, L. 2011. Diet, nutrition and telomere length. The Journal of Nutritional Biochemistry 22(10): 895-901.

Pietarinen, P., Pemovska, T., Kontro, M., Yadav, B., Mpindi, J., Andersson, E., Majumder, M.M., Kuusanmäki, H., Koskenvesa, P., Kallioniemi, O., Wennerberg, K., Heckman, C.A., Mustjoki, S. & Porkka, K. 2015. Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing. Blood Cancer Journal 5(5): e309.

Quintas-Cardama, A., Kantarjian, H. & Cortes, J. 2007. Flying under the radar: The new wave of BCR–ABL inhibitors. Nature Reviews Drug Discovery 6(10): 834-848.

Ranchoff, R.E. & Tomecki, K.J. 1986. Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference? Journal of the American Academy of Dermatology 15(1): 116-117.

Rouleau, M., Patel, A., Hendzel, M.J., Kaufmann, S.H. & Poirier, G.G. 2010. PARP inhibition: PARP1 and beyond. Nature Reviews Cancer 10(4): 293-301.

Shapira, S., Granot, G., Mor-Tzuntz, R., Raanani, P., Uziel, O., Lahav, M. & Shpilberg, O. 2012. Second-generation tyrosine kinase inhibitors reduce telomerase activity in K562 cells. Cancer Letters 323(2): 223-231.

Shay, J.W. & Wright, W.E. 2004. Senescence and immortalization: Role of telomeres and telomerase. Carcinogenesis 26(5): 867-874.

Surjana, D., Halliday, G.M. & Damian, D.L. 2010. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. Journal of Nucleic Acids 2010: 157591. 

Surjana, D., Halliday, G.M. & Damian, D.L. 2013. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 34(5): 1144-1149.

Thompson, B.C., Surjana, D., Halliday, G.M. & Damian, D.L. 2014. Nicotinamide enhances repair of ultraviolet radiation‐induced DNA damage in primary melanocytes. Experimental Dermatology 23(7): 509-511.

Traister, A., Breitman, I., Bar-Lev, E., Zvibel, I., Harel, A., Halpern, Z. & Oren, R. 2005. Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells. Scandinavian Journal of Gastroenterology 40(10): 1226-1234.

Turunc Bayrakdar, E., Uyanikgil, Y., Kanit, L., Koylu, E. & Yalcin, A. 2014. Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ (1-42)-induced rat model of Alzheimer's disease. Free Radical Research 48(2): 146-158.

Vaziri, H., Dessain, S.K., Eaton, E.N., Imai, S.I., Frye, R.A., Pandita, T.K., Guarente, L. & Weinberg, R.A. 2001. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107(2): 149-159.

Virag, L. & Szabo, C. 2002. The therapeutic potential of poly (ADP-ribose) polymerase inhibitors. Pharmacological Reviews 54(3): 375-429.

Yarosh, D.B. 2004. DNA repair, immunosuppression, and skin cancer. Cutis. 74(5): 10-13.

Yildirim, R., Sincan, G., Pala, C., Dudukcu, M., Kaynar, L., Urlu, S.M., Kiki, İ., Erdem, F., Çetin, M., Gündoğdu, M. & Topdağı, Ö. 2016. Effects of imatinib, nilotinib and dasatinib on serum VEGF and VEGFR-1 levels in patients with chronic phase chronic myelogenous leukemia. European Journal of General Medicine 13(2): 111-115.

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