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Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes
Author(s) -
Moradzadeh Maliheh,
Tabarraei Alijan,
Sadeghnia Hamid Reza,
Ghorbani Ahmad,
Mohamadkhani Ashraf,
Erfanian Saiedeh,
Sahebkar Amirhossein
Publication year - 2018
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.26391
Subject(s) - propidium iodide , apoptosis , kaempferol , acute promyelocytic leukemia , viability assay , abcc1 , biology , cancer research , leukemia , microbiology and biotechnology , pi3k/akt/mtor pathway , chemistry , programmed cell death , immunology , biochemistry , retinoic acid , flavonoid , gene , antioxidant , atp binding cassette transporter , transporter
Acute promyelocytic leukemia (APL) is one of the most life‐threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro‐apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti‐tumor properties. This study was designed to investigate the cytotoxic, pro‐apoptotic, and differentiation‐inducing effects of kaempferol on HL‐60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5‐100 μM) and all‐ trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML‐RAR and HDAC1), and multi‐drug resistance (ABCB1 and ABCC1) were determined using quantitative real‐time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL‐2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration‐dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients.