Effects of Nicotinamide and Nilotinib on Telomerase Activity and Telomere Length in K562 Myeloid Cell Line

Abstract

Chronic myelogenous leukaemia (CML) has continued to exist as a challenging disease even though advanced tyrosine kinase inhibitor therapy has been introduced. We study the effect of nicotinamide on telomerase activity, telomere length, and TERT expression in the K562 myeloid cell line as an approach to enhance the existing therapy for CML. However, the role of nicotinamide in tumorigenesis is controversial. We hypothesised that nicotinamide would enhance the effects of Nilotinib on K562 cells, hence reducing tumour growth and/or promoting tumour cell death. K562 cells were treated with nicotinamide, nilotinib and a combination of both for IC50 assay. This study has shown the effect of nicotinamide, nilotinib and both substances in exhibiting the anti-proliferation ability on the K562 cell line after 48 hours. The implicated mechanism involved in inducing such an effect is not yet clear. All treated samples exposed to all treatments have been assessed as telomerase-positive, suggesting that these treatments were most likely unable to repress telomerase activity in K562 cells. Except for nicotinamide, which slightly reduces telomerase activity and shortens telomeres, all treatment groups result in longer telomere lengths. Expression of TERT in this study suggests that the effect of these substances on telomerase activity is necessarily dependent on its impact on TERT expression. However, no study has been done to investigate the effect of nicotinamide in combination with nilotinib on telomerase and telomere regulation, and thus, further investigation on these substances is warranted.