In vitro cytotoxicity of Artemisia vulgaris L. essential oil is mediated by a mitochondria-dependent apoptosis in HL-60 leukemic cell line

BMC Complementary and Alternative Medicine

Research Article

Amre Nasr¹  Ahmad Aljada²  Ayman M Saleh²  Syed AA Rizvi³  Jack D Williams⁴  Ahmed S Alaskar⁵ 

[1] College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia;College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia;King Abdullah International Medical Research Center (KAIMRC), P.O. Box: 3660, 11481, Riyadh, Saudi Arabia;College of Pharmacy, Nova Southeastern University (NSU), Fort Lauderdale, Florida, USA;Department of Chemistry and Biochemistry, Mercyhurst University, Erie, PA, USA;King Abdullah International Medical Research Center (KAIMRC), P.O. Box: 3660, 11481, Riyadh, Saudi Arabia;Division of Adult Hematology & HSCT, Department of Oncology, King Abdulaziz Medical City, P.O. Box 22490, 11426, Riyadh, Saudi Arabia;

关键词: Artemisia vulgaris;    Essential oil;    Cytotoxicity;    Apoptosis;    Mitochondria;    Caspases;    Bcl-2 family;   

DOI  :  10.1186/1472-6882-14-226

 received in 2014-03-14, accepted in 2014-06-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe essential oil (EO) of Artemisia vulgaris L. has been traditionally used worldwide for treating a large number of diseases. Although major components in A. vulgaris EO have been shown to inhibit growth of different cancer cells, as pure compounds or part of other plants extracted oil, no information is known about its anti-proliferative activities. Therefore, the current investigation has evaluated the toxicity of the plant extracted oil from buds (AVO-b) and leaves (AVO-l) and characterized their growth inhibitory effects on cancer cells.MethodsAVO-b and AVO-l from A. vulgaris L. were extracted by hydrodistillation, and their effect on the viability of human HL-60 promyelocytic leukemia and various other cancer cell lines was tested using MTT assay. Flow cytometric analysis of apoptosis, DNA fragmentation assay, caspases enzymatic activities and Western blotting were used to determine the apoptotic pathway triggered by their action on HL-60 cells.ResultsLow concentrations of AVO-b and AVO-l inhibited the growth of HL-60 cells in a dose- and time-dependent manner. Employing flow cytometric, DNA fragmentation and caspase activation analyses, demonstrated that the cytotoxic effect of the oils is mediated by a caspase-dependent apoptosis. Kinetic studies in the presence and absence specific caspase inhibitors showed that activation of caspase-8 was dependent and subsequent to the activation of caspases-9 and -3. In addition, the essential oil caused a disruption of the mitochondrial transmembrane potential (ΔΨm), increased the release of cytochrome c to the cytosol, and altered the expression of certain members of Bcl-2 family (Bcl-2, Bax and Bid), Apaf-1 and XIAP. Interestingly, low doses of AVO-b and AVO-1 also induced apoptosis in various cancer cell lines, but not in noncancerous cells.ConclusionsThe results demonstrate that the EO-induced apoptosis in HL-60 cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by Bcl-2/Bax/Bid-dependent loss of ΔΨm leading to release of cytochrome c to the cytoplasm to activate the caspase cascade. The finding that AVO-b and AVO-l are more efficient to induce apoptosis in different cancer cell lines than noncancerous cells, suggests that A. vulgaris might be a promising source for new anticancer agents.

【 授权许可】

CC BY   
© Saleh et al.; licensee BioMed Central Ltd. 2014