Induction of Apoptosis, Autophagy and Ferroptosis byandExtract in Leukemia and Multiple Myeloma Cell Lines.
Molecules. 2020 Oct 29 ;25(21). Epub 2020 Oct 29. PMID: 33138135
Aveen N Adham
andhave 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 ofandin 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.-Hexane, chloroform, ethyl acetate, and butanol fractions ofandexhibited cytotoxicity in CCRF-CEM and CEM/ADR 5000 cell lines at concentration range 0.001-100μg/mL with potential activity revealed by chloroform and ethyl acetate fractions. NCI-H929 displayed pronounced sensitivity towards(TCF) and(ACF) chloroform fractions with ICvalues of 6.49± 1.48 and 21.9 ± 0.69 μg/mL, respectively. TCF induced apoptosis in NCI-H929 cells with a higher ratio (71%), compared to ACF (50%) at 4 × IC. 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.andcould be considered as potential herbal drug candidates, which arrest cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.