title: Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway.
abstract: Matrine (C15H24N2O), 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.
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Dachang
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Duoming
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ji
authors.affiliation: Department of General Surgery, Pingliang City People's Hospital, PingLiang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Galactophore, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Li
authors.identifier: http://orcid.org/0000-0002-2922-7853
authors.initials: L
authors.lastname: Wu
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004734:Energy Metabolism; D006801:Humans; D008516:Medicine, Chinese Traditional / Q000379:methods*; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D011807:Quinolizines; D000093842:Matrines
keywords: ER-positive MCF cells; endoplasmic reticulum stress; energy metabolism; hexokinase II; matrine