Antiproliferative, cytotoxic and apoptotic activity of the bentonite transformation of sesquiterpene lactone glaucolide B to 5β-hydroxy-hirsutinolide on tumor cell lines
| Autor: | Luis Sánchez-Sánchez, Mayra Espinosa-Trejo, Fernando Flores-Guzmán, Manuel Jiménez-Estrada, J. Javier Alvarado-Sansininea, Hugo López-Muñoz, Rosario Tavera-Hernández, María L. Escobar |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Lymphocyte Antineoplastic Agents Apoptosis Sesquiterpene lactone Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Lactate dehydrogenase medicine Humans Cytotoxic T cell Cell Proliferation bcl-2-Associated X Protein Pharmacology chemistry.chemical_classification medicine.diagnostic_test Caspase 3 Molecular biology Caspase 9 HaCaT 030104 developmental biology medicine.anatomical_structure chemistry Bentonite Sesquiterpenes 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Pharmacology. 856:172406 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2019.172406 |
| Popis: | Numerous chemical compounds isolated from medicinal plants have anti-tumor properties, the effects of which on human cancer cells are currently under study. Here, the chemical transformation of glaucolide B were performed to produce a hirsutinolide. The antiproliferative and cytotoxic activity of 5β-hydroxy-hirsutinolide and its ability to induce apoptosis in tumor and non-tumor cells (lymphocyte cultures and the normal HaCaT cell line) (1a) are reported. We ascertained that compound 1a exerts an inhibitory effect on the proliferation of SK-Lu-1, MDA-MB-231 and CaSki cells in a dose-dependent manner at IC50 values of 15, 18 and 30 μg/ml, respectively. The proliferation of lymphocyte cells treated with 1a was inhibited at a range from 14 to 28%, but the HaCaT cell line was not affected, suggesting that compound 1a has a selective action. Cytotoxic activity was evaluated by detecting the lactate dehydrogenase enzyme in supernatants from tumor and non-tumor cells. The 1a compound exhibited low or null cytotoxic activity in both cell types. The presence of apoptotic bodies and active caspase-3 in tumor cell lines treated with compound 1a are suggestive of apoptotic cell death. Notably, flow cytometry evaluation did not detect the presence of active caspase-3 on lymphocytes treated with this compound. Our results suggest that 5β-hydroxy-hirsutinolide is a molecule with antiproliferative activity and low cytotoxic activity in tumor and non-tumor cells; this induces apoptotic cell death in tumor cell lines through selective action. Hence, this lactone could be considered a molecule worthy of study as an anti-tumor agent with therapeutic potential. |
| Databáze: | OpenAIRE |
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