Abstract
Objective:Cancer is one of the leading causes of mortality in both developed and developing nations. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is characterized by its ability to selectively trigger apoptosis in cancer cells. TRAIL-based interventions have led to the development of recombinant human (rhTRAIL) as a promising therapy for different types of human cancer. Thymoquinone (TQ) has been shown to exert anticancer effect. The aim of the current study is to investigate the anticancer effect of the combinatorial therapy of TRAIL+TQ against human breast cancer cells. Methods:To achieve this hypothesis, cytotoxicity using MTT assay, as well as apoptosis and cell cycle using flow cytometric technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results:The current study showed that TRAIL induced cell cycle arrest and apoptosis. Moreover, it inhibited proliferation of MDA-MB-231 cells more than MCF-7 cells. Adding TQ to TRAIL increased the chemo-sensitivity of MDA-MB-231, while overcame the MCF-7 resistance to TRAIL. Conclusion:In conclusion, there is a synergistic effect between TRAIL and TQ playing a therapeutic role in killing resistant breast cancer cells.
Highlights
Cancer is one of the leading causes of mortality in both developed and developing nations
Dulbecco’s Modified Eagle Medium (DMEM), Roswell Park Memorial Institute (RPMI) 1640 medium, fetal bovine serum (FBS), penicillin/streptomycin (P/S), l-glutamine, trypsin/ EDTA, phosphate-buffered saline (PBS), and annexin V/ propidium iodide (PI) kit for apoptosis analysis, propidium iodide flow cytometry kit for cell cycle analysis were obtained from Life Technologies, Gibco (Grand Island, NY, USA)
Determination of anticancer potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or TQ against human breast cancer cell lines (MDA-MB-231 and MCF-7) by performing cytotoxicity assay to detect the reduction of MTT by mitochondrial dehydrogenase, which reflects the normal function of mitochondria and the measurement of cytotoxicity and cell viability
Summary
Cancer is one of the leading causes of mortality in both developed and developing nations. Breast cancer is known to be the second most common cause of mortality globally (Siegel et al, 2016). Chemotherapy drugs mainly work through injurious cellular nucleic acid. These types of cancer treatment contain many side effects that have a psychological, physical, and economic impact on the patient’s life (Puliyel et al, 2015). TRAIL is characterized by its ability to selectively trigger apoptosis in cancer cells but leaving normal cells healthy or with minimal effect (Turner et al, 2013). Qualifying as a potential drug specific for different types of cancer, containing breast, and liver (Szliszka et al, 2012; He et al, 2013; Cai Y et al, 2012; Bernardi et al, 2012); owing to its binding ability to the death receptors DR4 and DR5. TRAIL-based interventions have led to the development of recombinant human TRAIL (rhTRAIL) as a promising therapy for different types of human cancer (Strebel et al, 2001)
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