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Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro
Author(s) -
Zhang Yalan,
Xiao Yuhang,
Dong Qixing,
Ouyang Wenjuan,
Qin Qun
Publication year - 2019
Publication title -
journal of food science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 150
eISSN - 1750-3841
pISSN - 0022-1147
DOI - 10.1111/1750-3841.14484
Subject(s) - imatinib , myeloid leukemia , k562 cells , pharmacology , tyrosine kinase , lotus , salvia officinalis , medicine , traditional medicine , cancer research , chemistry , biology , leukemia , immunology , botany , receptor , officinalis
Imatinib, the prototype BCR‐ABL tyrosine kinase inhibitor (TKI), is the first‐line treatment for Philadelphia chromosome‐positive chronic myeloid leukemia (CML) in the chronic phase. However, a subgroup of patients exhibit poor response or experience relapse. This issue may be overcome by combination therapy using natural compounds. Neferine, a major bisbenzylisoquinoline alkaloid extracted from “lotus plumule” (seed embryo of lotus) commonly used in traditional Chinese medicine and tea, was used herein in the combination treatment of CML. The MTT assay showed that neferine exerted cytotoxicity in primary CML cells in a dose‐dependent manner. Moreover, low concentrations of neferine (4 and 8 µM) sensitized primary CML cells to imatinib (CI < 1), and significantly decreased its IC 50 from 0.70 ± 0.10 to 0.32 ± 0.06 µM and 0.16 ± 0.02 µM, respectively. Cotreatment of neferine and imatinib significantly decreased the expression of BCR‐ABL protein and its molecular chaperone heat shock protein 90 (Hsp90) mRNA and protein levels, and further decreased phospho‐extracellular regulated protein kinase 1/2 (p‐Erk1/2) and myeloid cell leukemia (Mcl‐1) expression. These results suggest that neferine might be a potential imatinib sensitizer in CML treatment. Practical application In China, Lotus plumule, the green embryo of lotus, is used as a tea and as a source of herbal medicine in the treatment of anxiety, insomnia, spermatorrhea, and thirst. Additional, neferine, a bisbenzylisoquinoline alkaloid extracted from lotus plumule has been shown to have antitumor potential. Herein, the effect of neferine and imatinib cotreatment on primary CML cells obtained from CML patients was assessed, with a synergistic effect being observed between the two compounds. Therefore, neferine might be a promising natural compound to potentiate imatinib in CML patients.