title: Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure-activity relationship.
abstract: This study has investigated the growth-inhibitory and apoptosis-inducing effects of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone on hematological malignancy cell lines, aiming to explore their structure-activity relationship. The growth-inhibitory effects of the tanshinones on K562 and Raji cells were assessed using a modified MTT assay; the apoptosis-inducing effects were assessed by fluorescence microscopy and flow cytometry analysis. The changes in cellular morphology were observed using an inverted phase-contrast microscope. MTT results revealed that these tanshinones inhibited cell proliferation in a concentration-dependent and time-dependent manner. The IC50 values of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone for K562 cells were 3.50, 13.52, 19.32, and 47.52 μmol/l at 24 h; 1.36, 4.70, 5.67, and 22.72 μmol/l at 48 h; and 1.15, 1.59, 2.82, and 19.53 μmol/l at 72 h, and the values for Raji cells were 3.30, 4.37, 12.92, and 52.36 μmol/l at 24 h; 1.55, 1.71, 6.54, and 25.45 μmol/l at 48 h; and 1.07, 1.38, 1.89, and 18.47 μmol/l at 72 h. The flow cytometry analysis demonstrated that these tanshinones induced apoptosis of K562 cells in a concentration-dependent manner, and dihydrotanshinone as well as tanshinone I were more potent than tanshinone IIA and cryptotanshinone. Some noticeable apoptotic morphologies could be observed by fluorescence microscopy on tanshinones-treated Raji cells. Collectively, these tanshinones caused growth inhibition and apoptosis in hematological malignancy cell lines, with dihydrotanshinone being the most potent, followed by tanshinone I, tanshinone IIA, and cryptotanshinone. These results suggested that the structure of aromatic ring A enhanced the cytotoxicity and the structure of ring C may have contributed to the cytotoxicity, but the mechanisms need to be further investigated.
authors.affiliation: State Key Laboratory of Biotherapy, Department of Hematology, West China Hospital, Sichuan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Chu
authors.forename: Hua-Yue
authors.initials: HY
authors.lastname: Shi
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Fu
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Wen-Tong
authors.initials: WT
authors.lastname: Meng
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Mao
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Jia
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010616:Phenanthrenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; C021751:tanshinone; C037886:cryptotanshinone