title: Mechanistic aspects of lauryl gallate-induced differentiation and apoptosis in human acute myeloid leukemia cells.
abstract: Lauryl gallate (LG) is a gallic acid derivative that has been widely used as an antioxidant food additive. In this study, we examined the anticancer effects of LG on the human acute myeloid leukemia (AML) HL60 and KG-1 cells. Our results showed that LG inhibited cell proliferation in a concentration- and time-dependent manner in both HL60 and KG-1 cells. The IC50s of LG in HL60 and KG-1 cells were 3.5 and 8.0 μM, respectively. Treatment with LG increased the proportions of annexin V-stained and sub-G1-phase HL60 and KG-1 cells. Moreover, activation of both extrinsic and intrinsic apoptotic pathways was involved in LG-induced AML cell apoptosis, accompanied by dissipation of mitochondrial membrane potential, downregulation of anti-apoptotic proteins (Bcl-2, Mcl-1, and Bcl-xL), upregulation of pro-apoptotic proteins (Bak, PUMA, DR4, and DR5), and increased caspase-2, -3, -8, and -9 activation. Our results also indicated that LG could induce monocytic differentiation in both HL60 and KG-1 cells, confirmed by morphological changes, nitroblue tetrazolium reduction assays, nonspecific esterase assays, and increased CD14 expression. After blocking LG-induced ERK and Sp1 expression using the ERK-specific inhibitor PD98059, monocytic differentiation in both HL60 and KG-1 cells decreased, suggesting that LG-induced differentiation proceeded through an ERK/Sp1 signaling axis.
authors.affiliation: Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan; Department of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 40201, Taiwan; Department of Life Science, Tunghai University, No. 1727, Taiwan Boulevard Sect. 4, Taichung 40704, Taiwan.
authors.forename: Chieh-Lin Jerry
authors.initials: CL
authors.lastname: Teng
authors.affiliation: Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan; Department of Life Science, National Chung Hsing University, No. 250, Guoguang Rd., Taichung 40227, Taiwan.
authors.forename: Shao-Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, No. 1, Daxue Rd., Puli Township, Nantou 545, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Wu
authors.affiliation: Department of Life Science, National Chung Hsing University, No. 250, Guoguang Rd., Taichung 40227, Taiwan.
authors.forename: Chi-Mei
authors.initials: CM
authors.lastname: Hsueh
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan.
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Tsai
authors.affiliation: Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan. Electronic address: kevinhwl@gmail.com.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Hwang
authors.affiliation: Department of Life Science, National Chung Hsing University, No. 250, Guoguang Rd., Taichung 40227, Taiwan; Department of Applied Chemistry, National Chi Nan University, No. 1, Daxue Rd., Puli Township, Nantou 545, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, Taichung 40705, Taiwan. Electronic address: h2326@vghtc.gov.tw.
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; C008259:lauryl gallate; D005707:Gallic Acid
keywords: Acute myeloid leukemia; Apoptosis; Differentiation; ERK; Lauryl gallate