title: β-Elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion.
abstract: β-elemonic acid, a known triterpene, exhibits anti-inflammatory effects, yet research on the pharmacological effects of β-elemonic acid is rare. We investigated the anticancer effects and the related molecular mechanisms of β-elemonic acid on human non-small cell lung cancer (NSCLC) A549 cells. The effects of β-elemonic acid on the growth of A549 cells were studied using a 3-(4,5)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using Annexin V staining. The effect of β-elemonic acid on the cell cycle of A549 cells was assessed using the propidium iodide method. The change in reactive oxygen species (ROS) was detected using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay with microscopic examination. The expression levels of Bcl-2 family proteins, mitogen-activated protein kinase (MAPK) family proteins and cyclooxygenase 2 (COX-2) were detected using western blot analysis. Our data revealed that β-elemonic acid strongly induced human A549 lung cancer cell death in a dose- and time-dependent manner as determined by the MTT assay. β-elemonic acid-induced cell death was considered to be apoptotic when the phosphatidylserine exposure was observed using Annexin V staining. The death of human A549 lung cancer cells was caused by apoptosis induced by activation of ROS activity, increase in the sub-G1 proportion, downregulation of Bcl-2 expression, upregulation of Bax expression and inhibition of the MAPK signaling pathways. These results clearly demonstrated that β-elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis. Moreover, the anticancer effects of β-elemonic acid were related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells.
authors.affiliation: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
authors.forename: Tsu-Tuan
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Division of Nephrology, Department of Medicine, Shin‑Kong Wu Ho‑Su Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Chien-Lin
authors.initials: CL
authors.lastname: Lu
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
authors.forename: Hen-I
authors.initials: HI
authors.lastname: Lin
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
authors.forename: Bing-Fang
authors.initials: BF
authors.lastname: Chen
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
authors.forename: Guey-Mei
authors.initials: GM
authors.lastname: Jow
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005978:Glutathione / Q000172:deficiency*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D005229:Fatty Acids, Monounsaturated; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C452499:elenic acid; D005978:Glutathione