Small molecules baicalein and cinnamaldehyde are potentiators of measles virus-induced breast cancer oncolysis |
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| Institution: | 1. Department of Medical Imaging, Chi Mei Medical Center, Tainan 71004, Taiwan;2. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;3. Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada;4. International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;5. Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China;2. College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China;1. School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024 China;2. School of Food and Environmental Science and Technology, Dalian University of Technology, Panjin, 124221 China;3. Department of Occupational and Environmental Health, Dalian Medical University, Dalian, 116044 China |
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| Abstract: | BackgroundAlthough the breast cancer mortality has slowed down from 2008 to 2017, breast cancer incidence rate continues to rise and thus, new and/or improved treatments are highly needed. Among them, oncolytic virotherapy which has the ability of facilitating the antitumor adaptive immunity, appears as a promising anticancer therapy. Oncolytic measles virus (MV) is particularly suitable for targeting breast cancer due to the upregulation of MV's receptor nectin-4. Nonetheless, with limited clinical success currently, ways of boosting MV-induced breast cancer oncolysis are therefore necessary. Oncolytic virotherapy alone and combined with chemotherapeutic drugs are two strategic areas with intensive development for the search of anticancer drugs. Considering that baicalein (BAI) and cinnamaldehyde (CIN) have demonstrated antitumor properties against multiple cancers including breast cancer, they could be good partners for MV-based oncolytic virotherapy.PurposeTo assess the in vitro effect of BAI and CIN with MV and assess their combination effects.MethodsWe examined the combinatorial cytotoxic effect of oncolytic MV and BAI or CIN on MCF-7 breast cancer cells. Potential anti-MV activities of the phytochemicals were first investigated in vitro to determine the optimal combination model. Synergism of MV and BAI or CIN was then evaluated in vitro by calculating the combination indices. Finally, cell cycle analysis and apoptosis assays were performed to confirm the mechanism of synergism.ResultsOverall, the viral sensitization combination modality using oncolytic MV to first infect MCF-7 breast cancer cells followed by drug treatment with BAI or CIN was found to produce significantly enhanced tumor killing. Further mechanistic studies showed that the combinations ‘MV-BAI’ and ‘MV-CIN’ display synergistic anti-breast cancer effect, mediated by elevated apoptosis.ConclusionWe demonstrated, for the first time, effective combination of oncolytic MV with BAI or CIN that could be further explored and potentially developed into novel therapeutic strategies targeting nectin-4-marked breast cancer cells. |
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