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Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1
Author(s) -
Pan Shan,
Leng Jun,
Deng Xinzhou,
Ruan Honggang,
Zhou Lu,
Jamal Muhammad,
Xiao Ruijing,
Xiong Jie,
Yin Qian,
Wu Yingjie,
Wang Meng,
Yuan Wen,
Shao Liang,
Zhang Qiuping
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29303
Subject(s) - sirtuin 1 , apoptosis , k562 cells , myeloid leukemia , cancer research , nad+ kinase , nicotinamide , chemistry , cell growth , leukemia , doxorubicin , gene knockdown , programmed cell death , pharmacology , biology , downregulation and upregulation , biochemistry , immunology , chemotherapy , enzyme , genetics , gene
The NAD‐dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD + precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX‐resistant K562 cells (K562R) in a dose‐dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX‐induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX‐induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase‐3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.