ABSTRACT
Cigarette smoking is a primary risk factor for chronic obstructive pulmonary disease (COPD), as it damages epithelial cells through a variety of mechanisms. Sulforaphane (SFN) is an antioxidant agent, which exerts protective effects against cell damage by activating the nuclear factor erythroid 2 like 2 (NFE2L2; Nrf2). The present study was undertaken to investigate the effects and underlying mechanisms of SFN in preventing cigarette smoke extract (CSE)induced oxidative damage to RLE6TN rat lung epithelial cells. MTT assay was used to determine the cytotoxicity of SFN and CSE. The effect of SFN and CSE on cell cycle progression, apoptosis and intracellular reactive oxygen species (ROS) levels were analyzed using flow cytometry. Reverse transcriptionquantitative polymerase chain reaction and western blotting were used to quantify mRNA and protein expression levels of Nrf2 respectively. SFN protected RLE6TN cells from oxidative damage, potentially via increasing Nrf2 expression and reducing ROS levels. In addition, SFN attenuated G1 phase cell cycle arrest and abrogated apoptosis. Therefore, SFN protected alveolar epithelial cells against CSEinduced oxidative injury by upregulating Nrf2 expression. The results of the present study may provide theoretical support for the clinical use of SFN in patients with COPD.
Subject(s)
Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Gene Expression Regulation/drug effects , Isothiocyanates/pharmacology , NF-E2-Related Factor 2/genetics , Nicotiana/adverse effects , Smoking/adverse effects , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Protective Agents/pharmacology , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Reactive Oxygen Species/metabolism , SulfoxidesABSTRACT
Seven new δ-tocotrienols, designated litchtocotrienols A-G (1-7), together with one glorious macrocyclic analogue, macrolitchtocotrienol A (8), and one new meroditerpene chromane, cyclolitchtocotrienol A (9), were isolated from the leaves of Litchi chinensis. Their structures were mainly determined by extensive spectroscopic analysis, and their biological activities were evaluated by cytotoxicity against human gastric adenocarcinoma cell lines (AGS, ATCC CRL-1739) and hepatoma carcinoma cell line (HepG2 2.2.1.5). The structure-activity relationship of the isolated compounds was also discussed.
Subject(s)
Chromans/chemistry , Chromans/pharmacology , Litchi/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Plant Leaves/chemistry , Structure-Activity RelationshipABSTRACT
BACKGROUND: Sulforaphane (SFN) is an excellent antioxidant agent, few of the studies focus on the possible protective role of SFN from cigarette smoke-induced injury on alveolar epithelial cells. OBJECTIVES: the aim of the study is to observe the possible protective role of SFN, as well as the function of insulin-like growth factor binding protein-3 (IGFBP-3) in the process. METHODS: MTT assay was used to evaluate cell viability after cigarette smoke extract (CSE) and/or SFN exposure, cell cycle was analyzed using flow cytometry, intracellular reactive oxygen species (ROS) level was detected by staining with fluorescent indicator 2', 7'-dichlorofluorescin diacetate (DCFH-DA), finally both real-time quantitative RT-PCR and western blot were employed to observe mRNA and protein levels of IGFBP-3. RESULTS: SFN could restore the viability of A549 cells, attenuate G1 block of the cell cycle, and significantly reduce the proportion of sub-G1 cells; at the same time, CSE-induced accumulation of intracellular ROS was decreased by SFN. Interestingly, high expression of IGFBP-3 was found at both transcriptional and translational levels, however by pre-incubation with SFN, the expression of IGFBP-3 was not stimulated by CSE exposure. CONCLUSIONS: SFN can antagonize CSE-induced growth arrest of alveolar epithelial cells and IGFBP-3 probably plays an important role in the process.
