Abstract

Introduction: Blast phase of chronic myelogenous leukaemia (CML) has continued to exist as a challenging disease even though the advanced tyrosine kinase inhibitor therapy has been introduced. We study the effect of nicotinamide (an active form of Vitamin B3) on telomerase activity, telomere length and TERT expression in the K562 myeloid cell line as an approach to enhance the existing therapy for CML. Yet the role of nicotinamide in tumorigenesis is controversial. We hypothesized that nicotinamide would enhance the effects of Nilotinib on K562 cells, hence reducing tumour growth and/or promoting tumour cell death. Methods: K562 cell line was treated with nicotinamide, nilotinib and combination of both for IC₅₀ assay. Detection of telomerase activity was carried out using TRAP assay, while qPCR assay was used for detection of telomere length and TERT expression. Results: This study has shown the effect of nicotinamide, nilotinib and both substances in exhibiting      the anti-proliferation ability on K562 cell line after 48 hours. The implicated mechanism involved to induce such an effect are not yet clear. All treated samples exposed by nicotinamide, nilotinib and both have been assessed as telomerase-positive suggesting that all treatments were most likely not able to repress telomerase activity in K562 cells. Data results in longer telomere length in all groups of treatments except for nicotinamide that have a slight      decrease of telomerase activity thus decrease in number of telomere length. Expression of TERT in this study suggests that the effect of these substances on telomerase activity is necessarily dependent on its effect on TERT expression. However, no study has been done to investigate the effect of nicotinamide in combination with nilotinib on telomerase and telomere regulation. Conclusion: The effects of nicotinamide and nilotinib on telomerase-telomere mechanisms may be linked to apoptosis which may give evidence for further investigation, notably in PARP-1 regulation.

Keywords: Nicotinamide, Nilotinib, Telomerase, Telomere, CML