The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells
Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heteroge...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science
2017
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/63490/ http://psasir.upm.edu.my/id/eprint/63490/1/The%20molecular%20mechanism%20of%20the%20anticancer%20effect%20of%20Artonin%20E%20in%20MDA-MB%20231%20triple%20negative%20breast%20cancer%20cells.pdf |
| _version_ | 1848854802107203584 |
|---|---|
| author | Etti, Imaobong Christopher Abdullah, Rasedee Kadir, Arifah Hashim, Najihah Mohd Swee, Keong Yeap Imam, Mustapha Umar Ramli, Faiqah Malami, Ibrahim Kian, Lim Lam Etti, Ubong Waziri, Peter Rahman, Marsitoh |
| author_facet | Etti, Imaobong Christopher Abdullah, Rasedee Kadir, Arifah Hashim, Najihah Mohd Swee, Keong Yeap Imam, Mustapha Umar Ramli, Faiqah Malami, Ibrahim Kian, Lim Lam Etti, Ubong Waziri, Peter Rahman, Marsitoh |
| author_sort | Etti, Imaobong Christopher |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer. |
| first_indexed | 2025-11-15T11:15:39Z |
| format | Article |
| id | upm-63490 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T11:15:39Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-634902018-11-04T23:51:05Z http://psasir.upm.edu.my/id/eprint/63490/ The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells Etti, Imaobong Christopher Abdullah, Rasedee Kadir, Arifah Hashim, Najihah Mohd Swee, Keong Yeap Imam, Mustapha Umar Ramli, Faiqah Malami, Ibrahim Kian, Lim Lam Etti, Ubong Waziri, Peter Rahman, Marsitoh Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer. Public Library of Science 2017 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/63490/1/The%20molecular%20mechanism%20of%20the%20anticancer%20effect%20of%20Artonin%20E%20in%20MDA-MB%20231%20triple%20negative%20breast%20cancer%20cells.pdf Etti, Imaobong Christopher and Abdullah, Rasedee and Kadir, Arifah and Hashim, Najihah Mohd and Swee, Keong Yeap and Imam, Mustapha Umar and Ramli, Faiqah and Malami, Ibrahim and Kian, Lim Lam and Etti, Ubong and Waziri, Peter and Rahman, Marsitoh (2017) The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells. PLOS ONE, 12 (8). pp. 1-20. ISSN 1932-6203 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182357 10.1371/journal.pone.0182357 |
| spellingShingle | Etti, Imaobong Christopher Abdullah, Rasedee Kadir, Arifah Hashim, Najihah Mohd Swee, Keong Yeap Imam, Mustapha Umar Ramli, Faiqah Malami, Ibrahim Kian, Lim Lam Etti, Ubong Waziri, Peter Rahman, Marsitoh The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title | The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title_full | The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title_fullStr | The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title_full_unstemmed | The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title_short | The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells |
| title_sort | molecular mechanism of the anticancer effect of artonin e in mda-mb 231 triple negative breast cancer cells |
| url | http://psasir.upm.edu.my/id/eprint/63490/ http://psasir.upm.edu.my/id/eprint/63490/ http://psasir.upm.edu.my/id/eprint/63490/ http://psasir.upm.edu.my/id/eprint/63490/1/The%20molecular%20mechanism%20of%20the%20anticancer%20effect%20of%20Artonin%20E%20in%20MDA-MB%20231%20triple%20negative%20breast%20cancer%20cells.pdf |