Premium
Matrine Suppresses the ER‐positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway
Author(s) -
Xiao Yi,
Ma Dachang,
Wang Honglei,
Wu Duoming,
Chen Ying,
Ji Kun,
Qin Tao,
Wu Li
Publication year - 2017
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5785
Subject(s) - endoplasmic reticulum , matrine , unfolded protein response , signal transduction , microbiology and biotechnology , chemistry , mcf 7 , energy metabolism , pharmacology , medicine , biology , cancer , human breast , chromatography , cancer cell
Matrine (C 15 H 24 N 2 O), an alkaloid that is one of the main active components from Sophora flavescens . Matrine has been demonstrated to have therapeutic effects on various solid tumors, including breast cancer, but the mechanism still needs further study. Endoplasmic reticulum (ER)‐positive Michigan Cancer Foundation cells were cultured, and matrine was added in various amounts to measure the dose‐dependent and time‐dependent cytotoxicity. Hoechst 33258 staining was used to observed nuclear morphological changes. Apoptosis was measured by AnnexinV/PI double staining assay kit. Intracellular adenosine triphosphate and glycometabolism were detected by assay kit. The protein levels GRP78, p‐eIF2α, CHOP, cytochrome c, and HexokinaseII were analyzed. Mechanistic investigations revealed that matrine treatment causes ER dilation and up‐regulated the expression of ER stress markers GRP78, eIF2α, and CHOP, increases the levels of apoptotic in Michigan Cancer Foundation cells, subsequently, blocking the ER stress‐mediated apoptosis pathway, significantly decreased matrine‐induced apoptotic but still has significant difference between control group. In addition, matrine not only promoted the occurrence of ER stress but also inhibited the expression of hexokinase II, down‐regulated energy metabolism. In summary, the present study suggests that the induction of ER stress‐mediated apoptosis by matrine and down‐regulated energy metabolism may account for its cytotoxic effects in human breast cancer cells. Copyright © 2017 John Wiley & Sons, Ltd.