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Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro


Citation

Mohan, Syam and Abdelwahab, Siddig Ibrahim and Cheah, Shiau Chuen and Sukari, Mohd Aspollah and Syam, Suvitha and Shamsuddin, Noorasyikin and Mustafa, Mohd Rais (2013) Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro. Evidence-Based Complementary and Alternative Medicine, 2013 (689865). pp. 1-12. ISSN 1741-427X; ESSN: 1741-4288

Abstract

Murraya koenigii Spreng has been traditionally claimed as a remedy for cancer. The current study investigated the anticancer effects of girinimbine, a carbazole alkaloid isolated from Murraya koenigii Spreng, on A549 lung cancer cells in relation to apoptotic mechanistic pathway. Girinimbine was isolated from Murraya koenigii Spreng. The antiproliferative activity was assayed using MTT and the apoptosis detection was done by annexin V and lysosomal stability assays. Multiparameter cytotoxicity assays were performed to investigate the change in mitochondrial membrane potential and cytochrome c translocation. ROS, caspase, and human apoptosis proteome profiler assays were done to investigate the apoptotic mechanism of cell death. The MTT assay revealed that the girinimbine induces cell death with an IC50 of 19.01 μM. A significant induction of early phase of apoptosis was shown by annexin V and lysosomal stability assays. After 24 h treatment with 19.01 μM of girinimbine, decrease in the nuclear area and increase in mitochondrial membrane potential and plasma membrane permeability were readily visible. Moreover the translocation of cytochrome c also was observed. Girinimbine mediates its antiproliferative and apoptotic effects through up- and downregulation of apoptotic and antiapoptotic proteins. There was a significant involvement of both intrinsic and extrinsic pathways. Moreover, the upregulation of p53 as well as the cell proliferation repressor proteins, p27 and p21, and the significant role of insulin/IGF-1 signaling were also identified. Moreover the caspases 3 and 8 were found to be significantly activated. Our results taken together indicated that girinimbine may be a potential agent for anticancer drug development.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Science
Institute of Bioscience
DOI Number: https://doi.org/10.1155/2013/689865
Publisher: Hindawi Publishing Corporation
Keywords: Apoptosis effect; Girinimbine; Murraya koenigii; Lung cancer cells.
Depositing User: Umikalthom Abdullah
Date Deposited: 19 Jun 2014 00:32
Last Modified: 07 Oct 2015 23:50
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1155/2013/689865
URI: http://psasir.upm.edu.my/id/eprint/30039
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