title: Validating antimetastatic effects of natural products in an engineered microfluidic platform mimicking tumor microenvironment.
abstract: Development of new, antimetastatic drugs from natural products has been substantially constrained by the lack of a reliable in vitro screening system. Such a system should ideally mimic the native, three-dimensional (3D) tumor microenvironment involving different cell types and allow quantitative analysis of cell behavior critical for metastasis. These requirements are largely unmet in the current model systems, leading to poor predictability of the in vitro collected data for in vivo trials, as well as prevailing inconsistency among different in vitro tests. In the present study, we report application of a 3D, microfluidic device for validation of the antimetastatic effects of 12 natural compounds. This system supports co-culture of endothelial and cancer cells in their native 3D morphology as in the tumor microenvironment and provides real-time monitoring of the cells treated with each compound. We found that three compounds, namely sanguinarine, nitidine, and resveratrol, exhibited significant antimetastatic or antiangiogenic effects. Each compound was further examined for its respective activity with separate conventional biological assays, and the outcomes were in agreement with the findings collected from the microfluidic system. In summary, we recommend use of this biomimetic model system as a new engineering tool for high-throughput evaluation of more diverse natural compounds with varying anticancer potentials.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Avenida Padre Tomas Pereira, Taipa, Macao SAR, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Niu
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D032701:Biomimetics / Q000379:methods*; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices / Q000379:methods; D044085:Microfluidics / Q000379:methods*; D008954:Models, Biological; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D001688:Biological Products; D007546:Isoquinolines; D013267:Stilbenes; C013615:nitidine; C005705:sanguinarine; D000077185:Resveratrol