Abstract
Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients.
Highlights
Breast cancer is a complex disease that results from the interaction of multiple environmental, hormonal, and lifestyle risk factors with the individual’s genome [1]
The CD50 value dropped to 0.50 ± 0.03 μg/mL, 0.20 ± 0.02 μg/mL and 0.12 ± 0.05 μg/mL when MCF-7 cells were exposed to 2.5 ± 0.12 μg/mL, 8.2 ± 0.07 μg/mL and 10.3 ± 0.15 μg/mL of damnacanthal, respectively
We found that the combination of damnacanthal and doxorubicin had a higher percentage of cells with hypo-diploid DNA content
Summary
Breast cancer is a complex disease that results from the interaction of multiple environmental, hormonal, and lifestyle risk factors with the individual’s genome [1]. Tamoxifen is the drug of choice in the treatment of estrogen receptor positive breast cancer [2]. Tamoxifen is the drug of choice in the treatment of estrogen receptor positive breast cancer, breast cancer patients are often treated with combinations of other drugs like doxorubicin for their treatment. Doxorubicin may be utilized after relapse in patients treated with tamoxifen or in patients with estrogen receptor negative breast cancer [4]. Doxorubicin is a powerful antitumoral drug and the effect of doxorubicin on tumor cells is mediated through multiple mechanisms. These include intercalation in DNA molecules, breaking of DNA strands by interaction with topoisomerase II, free radical formation and alteration of membrane structure [5]. According to Woods et al there are many factors that may influence the ultimate response to antitumor drugs in combination regimens like the clinical pharmacokinetics of the administered drugs, innate drug resistance and the extent of hormone dependency [6]
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