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

Received: 21 April 2019/Accepted: 7 January 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 mekanisma 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

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*Corresponding author; email: ssarina@usm.my