title: Cytotoxic effect and apoptotic mechanism of tanshinone A, a novel tanshinone derivative, on human erythroleukemic K562 cells.
abstract: Tanshinone A is a novel derivative of phenanthrene-quinone extracted from Salvia miltiorrhiza BUNGE, a traditional herbal medicine. Cytotoxic effect of tanshinone A was observed in this study. Additionally its mechanism of promoting apoptosis was also investigated. MTT and SRB assays were applied to measure the effects of tanshinone A on the cell viability, the cell cycle distribution and cell apoptosis were measured by flow cytometry using PI staining and Annexin V/PI double staining method respectively. The changes of mitochondrial membrane potential were also detected by flow cytometry. Spectrophotometric method was used to detect the changes of caspase-3 activity. Western blotting assay was used to evaluate the expression of bcl-2, bax and c-Myc proteins. Results indicated that tanshinone A displayed a significant inhibitory effect on the growth of K562 cells in a dose- and time-dependent manner, and showed obvious minor damage to LO2 cells. Tanshinone A could arrest K562 cells in the G(0)/G(1) phase and induce apoptosis, decrease the mitochondrial transmembrane potential, decrease the expressions of bcl-2 and c-Myc proteins, increase the expression of bax protein and the activity of caspase-3. Accordingly, it was presumed that the apoptosis induction may be through the endogenous pathway. Subsequently, tanshinone A could be a promising candidate in the development of a novel antitumor agent.
authors.affiliation: Department of Physiology, China Pharmaceutical University, Mailbox 207, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhen
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Yun-Man
authors.initials: YM
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: Teng
authors.initials: T
authors.lastname: Guan
authors.forename: Xu-Zhen
authors.initials: XZ
authors.lastname: Tang
mesh_terms: D045784:Abietanes / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; C021751:tanshinone; D053148:Caspase 3