Antiproliferative Effects of Nerium oleander Stem and Mitotic Ar rest Induced by Cardenolide Odoroside B on NCI-H460 Cancer Cells
| Autor: | Sabira Begum, Naseema Khatoon, Nurul Kabir, Kehkashan Arshad Qamar, Bina S. Siddiqui, Shaista Erum, Shakil Ahmed, Ahsana Dar Farooq |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Nerium oleander Pharmaceutical Science Pharmacology Nci h460 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug Discovery Cancer cell Cardenolide Molecular Medicine Mitosis Rest (music) |
| Zdroj: | Letters in Drug Design & Discovery. 15:84-94 |
| ISSN: | 1570-1808 |
| DOI: | 10.2174/1570180814666170727142145 |
| Popis: | Background: Nerium oleander extract preparations have been used in the Arab folkmedicine for the treatment of solid tumors. Objective: In the current investigation, bioassay-guided fractionation of N. oleander stem methanolic extract was performed to identify the active compound(s) responsible for its antiproliferative activity and the mechanism of action of the active compounds was explored. Methods: The methanolic extract, fractions and sub-fractions were screened against four human cancer cell lines: HT-144, MCF-7, NCI-H460 and SF-268 using sulforhodamine B assay. The effects of the active compounds on the cytoskeleton and nuclei of NCI-H460 cells were studied using immunofluorescence microscopy. Results: The more active petroleum ether insoluble sub-fraction led to the isolation of five pure compounds viz adynergenin, adynerin, hemidesmin-2, odoroside A and odoroside B. Odoroside A was the most potent compound with GI50: 0.04 and LC50: 0.74 µM against NCI-H460 cell line, while odoroside B demonstrated moderate growth inhibition and cytotoxicity (GI50: 6.7; LC50: 54 µM). After 24 hours' treatment with odoroside B (50 µM) abnormal mitotic spindles were observed, while > 90% mitotic cells were arrested in the prophase stage. Conclusion: N. oleander stem possesses significant antiproliferative effects against the aforementioned cell lines and the cardenolide odoroside B induces mitotic arrest of NCI-H460 cells in the prophase stage. |
| Databáze: | OpenAIRE |
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