title: Nordamnacanthal potentiates the cytotoxic effects of tamoxifen in human breast cancer cells.
abstract: Tamoxifen (TAM) is the mainline drug treatment for breast cancer, despite its side effects and the development of resistance. As an alternative approach, in the present study a novel combination therapy was established through combining TAM with nordamnacanthal (NDAM) in order to investigate the additive effect of these drugs in MCF-7 human breast cancer cells. A significant dose-dependent reduction in cell viability and an increase in apoptosis were observed in the MCF-7 cells cotreated with TAM and NDAM compared with the untreated control cells or the cells treated with TAM and NDAM alone (P<0.05). The cytotoxic influence of the combination of TAM and NDAM was found to be two-fold that of the individual agents. Annexin V/propidium iodide double-staining revealed the typical nuclear features of apoptosis. Furthermore, an increase in the proportion of apoptotic, Annexin V-positive cells was observed with the combination therapy. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and the generation of reactive oxygen species. To the best of our knowledge, the findings of the present study are the first to suggest that combining TAM with NDAM may be a potential combination therapy for the treatment of breast cancer and may have the potential to minimize or eliminate the side effects associated with high doses of TAM.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Tamilselvan
authors.initials: T
authors.lastname: Subramani
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Faculty of Medicine and Health Science, School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Semenyih, Selangor 43500, Malaysia.
authors.forename: Wan Yang
authors.initials: WY
authors.lastname: Ho
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Chai Ling
authors.initials: CL
authors.lastname: Ho
authors.affiliation: Faculty of Applied Sciences, Universiti Teknologi Mara, Shah Alam, Selangor 40450, Malaysia.
authors.forename: Che Puteh
authors.initials: CP
authors.lastname: Osman
authors.affiliation: Faculty of Applied Sciences, Universiti Teknologi Mara, Shah Alam, Selangor 40450, Malaysia.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Nik Mohd Afizan Nik Abdul
authors.initials: NM
authors.lastname: Rahman
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
keywords: MCF-7; apoptosis; breast cancer; combination treatment; nordamnacanthal; tamoxifen