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

Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. 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...

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Bibliographic Details
Published in:Journal of ethnopharmacology 2016-07, Vol.187, p.195-204
Main Authors: Foo, Jhi Biau, Saiful Yazan, Latifah, Tor, Yin Sim, Wibowo, Agustono, Ismail, Norsharina, Armania, Nurdin, Cheah, Yoke Kqueen, Abdullah, Rasedee
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
bcl-2-Associated X Protein - genetics
Betulinic acid
Cancer
Cell Cycle - drug effects
Cell cycle arrest
Cell Line, Tumor
Cell Survival - drug effects
Dillenia suffruticosa
Dilleniaceae
Gene Expression Regulation, Neoplastic - drug effects
Humans
Mitogen-Activated Protein Kinase 3 - genetics
Mitogen-Activated Protein Kinase 8 - genetics
Plant Extracts - pharmacology
Plant Roots
Proto-Oncogene Proteins c-bcl-2 - genetics
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - metabolism
Tumor Suppressor Protein p53 - genetics
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Summary:Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. 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). 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. 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. The data suggest the potential application of DCM-DS in the treatment of triple-negative breast cancer. [Display omitted]
ISSN:0378-8741
1872-7573
DOI:10.1016/j.jep.2016.04.048