1. Germacranolides from Carpesium divaricatum : Some New Data on Cytotoxic and Anti-Inflammatory Activity.
- Author
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Kłeczek N, Malarz J, Gierlikowska B, Skalniak Ł, Galanty A, Kiss AK, and Stojakowska A
- Subjects
- Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents classification, Anti-Inflammatory Agents isolation & purification, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic classification, Antineoplastic Agents, Phytogenic isolation & purification, Asteraceae metabolism, Cell Line, Cell Line, Tumor, Cell Survival drug effects, Chemokine CCL2 genetics, Chemokine CCL2 immunology, Cytotoxins chemistry, Cytotoxins classification, Cytotoxins isolation & purification, Doxorubicin pharmacology, Gene Expression Regulation, Neoplastic, Humans, Inhibitory Concentration 50, Interleukin-1beta genetics, Interleukin-1beta immunology, Interleukin-8 genetics, Interleukin-8 immunology, Lipopolysaccharides antagonists & inhibitors, Lipopolysaccharides pharmacology, Neutrophils cytology, Neutrophils drug effects, Neutrophils immunology, Plant Components, Aerial chemistry, Plant Components, Aerial metabolism, Plant Extracts chemistry, Plants, Medicinal, Poland, Primary Cell Culture, Sesquiterpenes, Germacrane chemistry, Sesquiterpenes, Germacrane classification, Sesquiterpenes, Germacrane isolation & purification, Signal Transduction, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha immunology, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 immunology, Anti-Inflammatory Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Asteraceae chemistry, Cytotoxins pharmacology, Sesquiterpenes, Germacrane pharmacology
- Abstract
Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro is the most frequently described biological activity of the compounds. However, little is known about the selectivity of the cytotoxic effect. The anti-inflammatory activity of the germacranolides is also poorly documented. The objective of the present study was to assess the cytotoxic activity of selected C. divaricatum germacranolides-derivatives of 4,5,8,9-tetrahydroxy-3-oxo-germacran-6,12-olide towards cancer and normal cell lines (including cells of different p53 status). Moreover, to assess the anti-inflammatory effect of the compounds, the release of four proinflammatory cytokines/chemokines (IL-1β, IL-8, TNF-α and CCL2) by lipopolysaccharide-stimulated human neutrophils was measured by ELISA. The investigated sesquiterpene lactones demonstrated nonselective activity towards prostate cancer (Du145 and PC3) and normal prostate epithelial cells (PNT2) as well as against melanoma cells (A375 and HTB140) and keratinocytes (HaCaT). Cytotoxic activity against osteosarcoma cells was independent of their p53 status. In sub-cytotoxic concentrations (0.5-2.5 µM) the studied compounds significantly decreased cytokine/chemokine release by lipopolysaccharide-stimulated human leukocytes.
- Published
- 2021
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