Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells
Ethnopharmacological Relevance: Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Aim of The Study: Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been r...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/55530/1/Dillenia%20suffruticosa%20dichloromethane%20root%20extract%20induced%20apoptosis%20towards%20MDA-.pdf |
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| author | Foo, J. B. Saiful Yazan, Latifah Tor, Yin Sim Wibowo, Agustono Ismail , N. Nurdin, Armania Cheah, Yoke Kqueen Abdullah, Rasedee |
| author_facet | Foo, J. B. Saiful Yazan, Latifah Tor, Yin Sim Wibowo, Agustono Ismail , N. Nurdin, Armania Cheah, Yoke Kqueen Abdullah, Rasedee |
| author_sort | Foo, J. B. |
| collection | UPM |
| description | Ethnopharmacological Relevance:
Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia.
Aim of The Study:
Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS).
Methods:
Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay.
Results:
DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM-DS.
Conclusion:
The data suggest the potential application of DCM-DS in the treatment of triple-negative breast cancer. |
| first_indexed | 2024-03-06T09:23:41Z |
| format | Article |
| id | upm.eprints-55530 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:23:41Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-555302017-09-13T03:04:27Z http://psasir.upm.edu.my/id/eprint/55530/ Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells Foo, J. B. Saiful Yazan, Latifah Tor, Yin Sim Wibowo, Agustono Ismail , N. Nurdin, Armania Cheah, Yoke Kqueen Abdullah, Rasedee Ethnopharmacological Relevance: Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Aim of The Study: Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS). Methods: Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay. Results: DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM-DS. Conclusion: The data suggest the potential application of DCM-DS in the treatment of triple-negative breast cancer. Elsevier 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/55530/1/Dillenia%20suffruticosa%20dichloromethane%20root%20extract%20induced%20apoptosis%20towards%20MDA-.pdf Foo, J. B. and Saiful Yazan, Latifah and Tor, Yin Sim and Wibowo, Agustono and Ismail , N. and Nurdin, Armania and Cheah, Yoke Kqueen and Abdullah, Rasedee (2016) Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells. Journal of Ethnopharmacology, 187. pp. 195-204. ISSN 0378-8741; ESSN: 1872-7573 10.1016/j.jep.2016.04.048 |
| spellingShingle | Foo, J. B. Saiful Yazan, Latifah Tor, Yin Sim Wibowo, Agustono Ismail , N. Nurdin, Armania Cheah, Yoke Kqueen Abdullah, Rasedee Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title | Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title_full | Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title_fullStr | Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title_full_unstemmed | Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title_short | Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells |
| title_sort | dillenia suffruticosa dichloromethane root extract induced apoptosis towards mda mb 231 triple negative breast cancer cells |
| url | http://psasir.upm.edu.my/id/eprint/55530/1/Dillenia%20suffruticosa%20dichloromethane%20root%20extract%20induced%20apoptosis%20towards%20MDA-.pdf |
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