Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines
Autor: | Alaadin M. Naqishbandi, Mohamed-Elamir F. Hegazy, Thomas Efferth, Aveen Nozad Adham |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Programmed cell death
autophagy Thymus vulgaris Pharmaceutical Science Nobiletin Analytical Chemistry lcsh:QD241-441 lamiaceae 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ursolic acid lcsh:Organic chemistry Drug Discovery asteraceae Physical and Theoretical Chemistry Cytotoxicity 030304 developmental biology 0303 health sciences biology Organic Chemistry apoptosis phytotherapy biology.organism_classification Molecular biology ferroptosis multiple myeloma cell death chemistry Chemistry (miscellaneous) Apoptosis 030220 oncology & carcinogenesis Arctium lappa Apigenin Molecular Medicine |
Zdroj: | Molecules Volume 25 Issue 21 Molecules, Vol 25, Iss 5016, p 5016 (2020) |
ISSN: | 1420-3049 |
DOI: | 10.3390/molecules25215016 |
Popis: | Thymus vulgaris and Arctium lappa have been used as a folk remedy in the Iraqi Kurdistan region to deal with different health problems. The aim of the current study is to investigate the cytotoxicity of T. vulgaris and A. lappa in leukemia and multiple myeloma (MM) cell lines and determine the mode of cell death triggered by the most potent cytotoxic fractions of both plants in MM. Resazurin assay was used to evaluate cytotoxic and ferroptosis activity, apoptosis, and modulation in the cell cycle phase were investigated via Annexin V-FITC/PI dual stain and cell-cycle arrest assays. Furthermore, we used western blotting assay for the determination of autophagy cell death. n-Hexane, chloroform, ethyl acetate, and butanol fractions of T. vulgaris and A. lappa exhibited cytotoxicity in CCRF-CEM and CEM/ADR 5000 cell lines at concentration range 0.001&ndash 100 &mu g/mL with potential activity revealed by chloroform and ethyl acetate fractions. NCI-H929 displayed pronounced sensitivity towards T. vulgaris (TCF) and A. lappa (ACF) chloroform fractions with IC50 values of 6.49 ± 1.48 and 21.9 ± 0.69 &mu g/mL, respectively. TCF induced apoptosis in NCI-H929 cells with a higher ratio (71%), compared to ACF (50%) at 4 × IC50. ACF demonstrated more potent autophagy activity than TCF. TCF and ACF induced cell cycle arrest and ferroptosis. Apigenin and nobiletin were identified in TCF, while nobiletin, ursolic acid, and lupeol were the main compounds identified in ACF. T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis. |
Databáze: | OpenAIRE |
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