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Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells


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


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.

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Additional Metadata

Item Type: Article
DOI Number: https://doi.org/10.1016/j.jep.2016.04.048
Publisher: Elsevier
Keywords: Apoptosis; Betulinic acid; Cancer; Cell cycle arrest; Dillenia suffruticosa
Depositing User: Mohd Hafiz Che Mahasan
Date Deposited: 13 Sep 2017 03:04
Last Modified: 13 Sep 2017 03:04
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.jep.2016.04.048
URI: http://psasir.upm.edu.my/id/eprint/55530
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