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 μ M. A significant induction of early phase of apoptosis was shown by
annexin V and lysosomal stability assays. After 24 h treatment with 19.01 μ M 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.