The sesquiterpene lactone polymatin B from Smallanthus sonchifolius induces different cell death mechanisms in three cancer cell lines

被引:32
作者
De Ford, Christian [1 ,2 ]
Ulloa, Jeronimo L. [3 ]
Catalan, Cesar A. N. [4 ]
Grau, Alfredo [5 ]
Martino, Virginia S. [3 ]
Muschietti, Liliana V. [3 ]
Merfort, Irmgard [1 ,2 ]
机构
[1] Univ Freiburg, Fac Chem & Pharm, Dept Pharmaceut Biol & Biotechnol, D-79104 Freiburg, Germany
[2] Univ Freiburg, Spemann Grad Sch Biol & Med SGBM, Dept Pharmaceut Biol & Biotechnol, D-79104 Freiburg, Germany
[3] Univ Buenos Aires, Fac Farm & Bioquim, CONICET, Catedra Farmacognosia,IQUIMEFA, RA-1113 Buenos Aires, DF, Argentina
[4] UNT, Fac Bioquim Quim & Farm, INQUINOA, CONICET, San Miguel De Tucuman, Tucuman, Argentina
[5] Univ Nacl Tucuman, IER, Fac Ciencias Nat, RA-4107 Yerba Buena, Tucuman, Argentina
关键词
Smallanthus sonchifolius; Asteraceae; Sesquiterpene lactones; Cytotoxicity; OCCURRING TERPENE DERIVATIVES; CYTO-TOXICITY; MELAMPOLIDES; CONSTITUENTS; GERMACRANOLIDES; LEAVES; ASSAY; GUAIANOLIDES; INHIBITION; APOPTOSIS;
D O I
10.1016/j.phytochem.2015.06.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
A 8 beta-angeloyloxy-9 alpha-hydroxy-14-oxo-acanthospermolide and five known melampolide sesquiterpene lactones (uvedalin, enhydrin, polymatin B, sonchifolin, and fiuctuanin) were isolated from the leaves of Smallanthus sonchifolius. The compounds were identified by 1D-, 2D-NMR, HRMS, IR and UV analyses. In vitro cytotoxicity assays (MTT) showed that these sesquiterpene lactones display poor cytotoxic effects on peripheral blood mononuclear cells (PBMC) of healthy human subjects, whereas a strong cytotoxicity was observed in leukemia and pancreas cancer cells. For the mechanism of action of polymatin B, oxidative stress seems to be involved. Interestingly, reactive oxygen species (ROS) formation mainly induced different effects: apoptosis in CCRF-CEM cells, necroptosis in CEM-ADR5000 cells through induction of RIP1K, neither apoptosis nor necroptosis in MIA-PaCa-2 cells. Additionally, cells also died partly by necrosis. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:332 / 339
页数:8
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