Targeting peroxiredoxin I potentiates 1,25-dihydroxyvitamin D3-induced cell differentiation in leukemia cells
Wei, Wei1; Liu, Chuanxu1; Qin, Dongjun2; Song, Lili2; Xia, Li2; Lei, Hu2; Yu, Yun2; Wang, Weiwei2; Pu, Jianxin3; Sun, Handong3; Wu, Yingli2; Xu, Hanzhang2; Haw, Siguo1
2016-03-01
Source PublicationMOLECULAR MEDICINE REPORTS
Volume13Issue:3Pages:2201-2207
AbstractAlthough 1,25-dihydroxyvitamin D-3 (VD3) is regarded as a promising inducing agent for leukemia cell differentiation, it is not as effective an agent as all-trans-retinoic acid, and its usefulness is also limited by the adverse effects of hypercalcemia. The aim of the present study was to determine whether combining VD3 with adenanthin, a peroxiresoxin I (Prx I)-targeting natural compound, improves the efficacy of VD3. Cell viability was assessed using a trypan blue exclusion assay and flow cytometry was used to evaluate the expression of cell surface markers, CD11b/CD14, and the level of reactive oxygen species (ROS). Wright's staining was used to examine morphological changes and RNA-interference was used to knockdown Prx I and p65 gene expression. Protein expression was determined by western blot analysis. The results demonstrated that adenanthin markedly enhanced VD3-induced cell differentiation of leukemia NB4 cells, as evidenced by the increased percentage of CD11b- and CD14-positive cells, the mature morphology of the monocytes and the increased phagocytic ability. Consistent with these results, knockdown of Prx I, but not nuclear factor-B (p65), enhanced VD3-induced cell differentiation. The combinatorial effects of adenanthin and VD3 were shown to be associated with the ROS-CCAAT-enhancer-binding protein (C/EBP) axis, since N-acetylcysteine, a ROS scavenger, was able to abrogate the differentiation-enhancing effects of adenanthin, and the knockdown of C/EBP also inhibited the combinatorial effects of adenanthin and VD3. In addition, co-treatment with adenanthin and VD3 was able to induce differentiation in other non-acute promyelocytic leukemia cells and primary leukemia cells. In conclusion, the results of the present study revealed a novel role for Prx I in VD3-induced cell differentiation, and suggested that targeting Prx I may represent a novel strategy to enhance VD3-induced leukemia cell differentiation.
KeywordAdenanthin 1 25-dihydroxyvitamin D3 Leukemia Peroxiredoxin i Cell Differentiation
DOI10.3892/mmr.2016.4787
Indexed BySCI
Language英语
WOS IDWOS:000371633000034
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/26013
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Hematol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med,Chinese Minist Educ,E Inst, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol,Chem Biol Div,Shanghai Univ, 280 Chongqing South Rd, Shanghai 200025, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
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Wei, Wei,Liu, Chuanxu,Qin, Dongjun,et al. Targeting peroxiredoxin I potentiates 1,25-dihydroxyvitamin D3-induced cell differentiation in leukemia cells[J]. MOLECULAR MEDICINE REPORTS,2016,13(3):2201-2207.
APA Wei, Wei.,Liu, Chuanxu.,Qin, Dongjun.,Song, Lili.,Xia, Li.,...&Haw, Siguo.(2016).Targeting peroxiredoxin I potentiates 1,25-dihydroxyvitamin D3-induced cell differentiation in leukemia cells.MOLECULAR MEDICINE REPORTS,13(3),2201-2207.
MLA Wei, Wei,et al."Targeting peroxiredoxin I potentiates 1,25-dihydroxyvitamin D3-induced cell differentiation in leukemia cells".MOLECULAR MEDICINE REPORTS 13.3(2016):2201-2207.
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