title: Tanshinone IIA induces apoptosis in human lung cancer A549 cells through the induction of reactive oxygen species and decreasing the mitochondrial membrane potential.
abstract: Tanshinone IIA (Tan-IIA) is extracted from Danshen and known to inhibit proliferation and induce apoptosis in many cancer cells. We aimed to elucidate its anticancer activity and molecular mechanism in human lung cancer A549 cells. The cytotoxicity of Tan-IIA in A549 cells were measured by the MTT assay. The effects of Tan-IIA on the cell cycle, mitochondrial membrane potential (MMP), calcium and reactive oxygen species (ROS) released in A549 cells were detected by flow cytometry. The protein expressions of p53, Bax, Bcl-2 and beta-actin in A549 cells were tested by Western blotting. The proliferative rates of A549 cells were obviously inhibited by Tan-IIA in a dose- and time-dependent manner. The results of FACS showed that the sub-G1 phase was increased when A549 cells were cultured with various concentrations of Tan-IIA (control, 2.5, 5 and 10 microg/ml) for 48 h. Tan-IIA induced the production of ROS, Ca+2 and decreased MMP. The outcome of Western blotting showed that protein expressions of p53 and bax were increased, but proto-oncogene bcl-2 was notably decreased, after culturing with Tan-IIA (5 microg/ml) for 6, 12 and 24 h. Tan-IIA inhibited the proliferation of non-small cell lung cancer A549 cells, possibly by decreasing the MMP and inducing apoptosis due to the induction of a higher ratio of Bax/Bcl-2.
authors.affiliation: Institute of Medical Sciences, Hualien 97004, Taiwan, ROC.
authors.forename: Tsung-Lang
authors.initials: TL
authors.lastname: Chiu
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Su
mesh_terms: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000715470:MAS1 protein, human; D010616:Phenanthrenes; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C021751:tanshinone; D045304:Cytochromes c; D002118:Calcium