title: Aloe-Emodin Enhances Tamoxifen Cytotoxicity by Suppressing Ras/ERK and PI3K/mTOR in Breast Cancer Cells.
abstract: Aloe-emodin (AE) is derived from Aloe vera and rhubarb (Rheum palmatum) and exhibits anticancer activities via multiple regulatory mechanisms in various cancers. AE can also enhance the anticancer efficacy of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil; however, its effects remain poorly characterized. MCF-7, MDA-MB-231, MDA-MB-468, BT-474, and HCC-1954 breast cancer cell lines were treated with the indicated conditions of AE, and cell viability assays were performed. The expression levels of signaling proteins were determined by western blot analysis, intracellular reactive oxygen species (ROS), cell cycle distributions, and rates of apoptosis as estimated by flow cytometry. In comparison with other cells, MCF-7 cells were more sensitive to AE treatment; AE enhanced the cytotoxicity of 9[Formula: see text][Formula: see text]g/ml tamoxifen by reducing EGFR, ER[Formula: see text], Ras, ERK, c-Myc, and mTOR protein expression and blocking PI3K and mTOR activation. Finally, although co-treatment of AE with tamoxifen increased intracellular ROS, there were no effects on cell cycle progression. Besides facilitating tamoxifen-induced cell death, AE also enhanced the antiproliferative activity of tamoxifen by blocking Ras/ERK and PI3K/mTOR pathways in breast cancer cells, thus demonstrating the chemosensitizing potential of AE.
authors.affiliation: * Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.|‡ Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan.
authors.forename: Hsin-Shun
authors.initials: HS
authors.lastname: Tseng
authors.affiliation: † Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Wang
authors.affiliation: ‡ Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan.|¶ Department of Life Science, National Taitung University, Taitung, Taiwan.|∥ Center for General Education, National Taitung University, Taitung, Taiwan.
authors.forename: Yew-Min
authors.initials: YM
authors.lastname: Tzeng
authors.affiliation: * Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.|† Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Dar-Ren
authors.initials: DR
authors.lastname: Chen
authors.affiliation: ‡ Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan.|§ Asia Mycotoxin Analysis Center, Chaoyang University of Technology, Taichung, Taiwan.
authors.forename: Ya-Fan
authors.initials: YF
authors.lastname: Liao
authors.affiliation: * Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.|** School of Nursing, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Chiu
authors.affiliation: †† Department of Pharmacology, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Tsong
authors.initials: WT
authors.lastname: Hsieh
mesh_terms: D000504:Aloe / Q000737:chemistry; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics*; D004357:Drug Synergism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012250:Rheum / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; D013629:Tamoxifen; D018631:ras Proteins; C518327:aloe emodin; C546842:MTOR protein, human
keywords: Aloe-Emodin; Breast Cancer; Chemosensitization; ERK; PI3K; Tamoxifen; mTOR