RRC ID 45007
Author Kikuchi T, Ishii K, Ogihara E, Zhang J, Ukiya M, Tokuda H, Iida T, Tanaka R, Akihisa T.
Title Cytotoxic and apoptosis-inducing activities, and anti-tumor-promoting effects of cyanogenated and oxygenated triterpenes.
Journal Chem Biodivers
Abstract Two of each semisynthetic lanostane- and cycloartane-type triterpenes with a cyano-enone functionality, i.e., 13 and 18, and 23 and 28, respectively, sixteen of their synthetic intermediates, 9-12, 14-17, 19-22, and 24-27, along with seven semisynthetic oxygenated triterpene acetates, 29-35, and eight natural hydroxy triterpenes, 1-8, were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines. One natural triterpene, 8, and ten semisynthetic triterpenes, 9, 13, 15, 18, 23, 25, 28, 29, 32, and 33, exhibited potent cytotoxicities against one or more cell lines with IC50 values in the range of 1.4-9.9 μM. Two lanostane-type triterpenes with a cyano-enone functionality, 3-oxolanosta-1,8,24-triene-2-carbonitrile (13) and 3-oxolanosta-1,8-diene-2-carbonitrile (18), induced apoptosis in HL60 cells, as observed by membrane phospholipid exposure in flow cytometry. Western blot analysis showed that 13 and 18 significantly reduced procaspases-3, -8, and -9, and increased cleaved caspases-3, -8, and -9. These findings indicated that compounds 13 and 18 induced apoptosis in HL60 cells via both the mitochondrial and the death receptor-mediated pathways. In addition, upon evaluation of the inhibitory effects on EpsteinBarr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, seven natural triterpenes, 1-6 and 8, and ten semisynthetic triterpenes, 9, 10, 14, 15, 19, 20, 24, 25, 29, and 30, exhibited inhibitory effects which were higher than that of β-carotene, a vitamin A precursor studied widely in cancer-chemoprevention animal models.
Volume 11(4)
Pages 491-504
Published 2014-4-1
DOI 10.1002/cbdv.201300395
PMID 24706621
MeSH Antigens, Viral / metabolism Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects* Caspases / metabolism Cell Line, Tumor Chemistry Techniques, Synthetic Drug Screening Assays, Antitumor HL-60 Cells / drug effects Humans Inhibitory Concentration 50 Structure-Activity Relationship Tetradecanoylphorbol Acetate / pharmacology Triterpenes / chemical synthesis Triterpenes / chemistry* Triterpenes / pharmacology*
IF 1.449
Times Cited 5
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CHEMISTRY, MULTIDISCIPLINARY
Resource
Human and Animal Cells