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

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 iso...

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Main Authors: Mohan, Syam, Abdelwahab, Siddig Ibrahim, Cheah, Shiau Chuen, Sukari, Mohd Aspollah, Syam, Suvitha, Shamsuddin, Noorasyikin, Mustafa, Mohd Rais
Format: Article
Language:English
English
Published: Hindawi Publishing Corporation 2013
Online Access:http://psasir.upm.edu.my/id/eprint/30039/1/Apoptosis%20effect%20of%20girinimbine%20isolated%20from%20Murraya%20koenigii%20on%20lung%20cancer%20cells%20in%20vitro.pdf
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author Mohan, Syam
Abdelwahab, Siddig Ibrahim
Cheah, Shiau Chuen
Sukari, Mohd Aspollah
Syam, Suvitha
Shamsuddin, Noorasyikin
Mustafa, Mohd Rais
author_facet Mohan, Syam
Abdelwahab, Siddig Ibrahim
Cheah, Shiau Chuen
Sukari, Mohd Aspollah
Syam, Suvitha
Shamsuddin, Noorasyikin
Mustafa, Mohd Rais
author_sort Mohan, Syam
collection UPM
description 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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spelling upm.eprints-300392015-10-07T23:50:13Z http://psasir.upm.edu.my/id/eprint/30039/ Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro Mohan, Syam Abdelwahab, Siddig Ibrahim Cheah, Shiau Chuen Sukari, Mohd Aspollah Syam, Suvitha Shamsuddin, Noorasyikin Mustafa, Mohd Rais 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. Hindawi Publishing Corporation 2013 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/30039/1/Apoptosis%20effect%20of%20girinimbine%20isolated%20from%20Murraya%20koenigii%20on%20lung%20cancer%20cells%20in%20vitro.pdf 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 http://www.hindawi.com/journals/ecam/2013/689865/ 10.1155/2013/689865 English
spellingShingle Mohan, Syam
Abdelwahab, Siddig Ibrahim
Cheah, Shiau Chuen
Sukari, Mohd Aspollah
Syam, Suvitha
Shamsuddin, Noorasyikin
Mustafa, Mohd Rais
Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title_full Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title_fullStr Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title_full_unstemmed Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title_short Apoptosis effect of girinimbine isolated from Murraya koenigii on lung cancer cells in vitro
title_sort apoptosis effect of girinimbine isolated from murraya koenigii on lung cancer cells in vitro
url http://psasir.upm.edu.my/id/eprint/30039/1/Apoptosis%20effect%20of%20girinimbine%20isolated%20from%20Murraya%20koenigii%20on%20lung%20cancer%20cells%20in%20vitro.pdf
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