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

• Published in: Phytochemistry (Oxford) Vol. 117; pp. 332 - 339
• Main Authors: De Ford, Christian, Ulloa, Jerónimo L., Catalán, César A.N., Grau, Alfredo, Martino, Virginia S., Muschietti, Liliana V., Merfort, Irmgard
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2015; Elsevier
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; apoptosis; Asteraceae; Asteraceae - chemistry; Biochemistry & Molecular Biology; Cell Cycle - drug effects; Cell Death - drug effects; Cell Line, Tumor - drug effects; Cytotoxicity; Drug Evaluation, Preclinical - methods; Drug Screening Assays, Antitumor - methods; Humans; Lactones - chemistry; Lactones - pharmacology; leaves; leukemia; Leukemia, T-Cell - drug therapy; Leukemia, T-Cell - pathology; Leukocytes, Mononuclear - drug effects; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; mechanism of action; Molecular Structure; mononuclear leukocytes; necrosis; neoplasm cells; nuclear magnetic resonance spectroscopy; oxidative stress; Oxidative Stress - drug effects; pancreatic neoplasms; Plant Sciences; reactive oxygen species; Science & Technology; Sesquiterpene lactones; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes, Germacrane - chemistry; Sesquiterpenes, Germacrane - pharmacology; sesquiterpenoid lactones; Smallanthus sonchifolius; Cytotoxicity; Sesquiterpene lactones; Smallanthus sonchifolius; Asteraceae; APOPTOSIS; ASSAY; LEAVES; OCCURRING TERPENE DERIVATIVES; INHIBITION; CYTO-TOXICITY; GUAIANOLIDES; GERMACRANOLIDES; MELAMPOLIDES; CONSTITUENTS
• ISSN: 0031-9422; 1873-3700; 1873-3700
• DOI: 10.1016/j.phytochem.2015.06.020

The sesquiterpene lactone polymatin B induces different mechanisms of cell death which is dependent on the cell type. Preferentially, cell death is promoted by inducing oxidative stress in cancer cells. [Display omitted] •An acanthospermolide sesquiterpene lactone (SL) has been identified in Smallanthus sonchifolius.•The SLs are highly cytotoxic against cancer cell lines, but not against PBMC cells.•Polymatin B induces different cell death mechanisms in the three cancer cell lines. A 8β-angeloyloxy-9α-hydroxy-14-oxo-acanthospermolide and five known melampolide sesquiterpene lactones (uvedalin, enhydrin, polymatin B, sonchifolin, and fluctuanin) 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.