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Open Access Highly Accessed Research article

Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa

Yin Sim Tor1, Latifah Saiful Yazan12*, Jhi Biau Foo1, Nurdin Armania1, Yoke Kqueen Cheah2, Rasedee Abdullah3, Mustapha Umar Imam1, Norsharina Ismail1 and Maznah Ismail1

Author Affiliations

1 Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

2 Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

3 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti, Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

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BMC Complementary and Alternative Medicine 2014, 14:55  doi:10.1186/1472-6882-14-55

Published: 14 February 2014

Abstract

Background

Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.

Methods

EADs was obtained from the root of D. suffruticosa by using sequential solvent extraction. Cytotoxicity was determined by using MTT assay, mode of cell death by cell cycle analysis and apoptosis induction by Annexin-FITC/PI assay. Morphology changes in cells were observed under inverted light microscope. Involvement of selected genes in the oxidative stress-mediated signaling pathway was explored using multiplex gene expression analysis.

Results

The treatment of EADs caused cytotoxicity to MCF-7 cells in a dose- and time-dependent manner at 24, 48 and 72 hours with IC50 of 76 ± 2.3, 58 ± 0.7 and 39 ± 3.6 μg/mL, respectively. The IC50 of tamoxifen-treated MCF-7 cells was 8 ± 0.5 μg/mL. Induction of apoptosis by EADs was dose- and time- dependent. EADs induced non-phase specific cell cycle arrest at different concentration and time point. The multiplex mRNA expression study indicated that EADs-induced apoptosis was accompanied by upregulation of the expression of SOD1, SOD2, NF-κB, p53, p38 MAPK, and catalase, but downregulation of Akt1.

Conclusion

It is suggested that EADs induced apoptosis in MCF-7 cells by modulating numerous genes which are involved in oxidative stress pathway. Therefore, EADs has the potential to act as an effective intervention against breast cancer cells.

Keywords:
Dillenia suffruticosa; Breast cancer; Cytotoxic; Apoptosis; Oxidative stress pathway