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- Title
Apoptosis Effect of Girinimbine Isolated from Murray a koenigii on Lung Cancer Cells In Vitro.
- Authors
Mohan, Syam; Abdelwahab, Siddig Ibrahim; Cheah, Shiau-Chuen; Sukari, Mohd Aspollah; Syam, Suvitha; Noorasyikin Shamsuddin; Mustafa, Mohd Rais
- 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 p2l, 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.
- Subjects
THERAPEUTIC use of plant extracts; ALKALOIDS; ANALYSIS of variance; APOPTOSIS; BIOLOGICAL assay; CELL surface antigens; CULTURES (Biology); DOSE-effect relationship in pharmacology; IMMUNODIAGNOSIS; LUNG cancer; AYURVEDIC medicine; MITOCHONDRIA; RESEARCH funding; SPECTRUM analysis; EMPIRICAL research; DATA analysis software; PROTEIN microarrays; DESCRIPTIVE statistics; CLASSIFICATION
- Publication
Evidence-based Complementary & Alternative Medicine (eCAM), 2013, Vol 2013, p1
- ISSN
1741-427X
- Publication type
Article
- DOI
10.1155/2013/689865