Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment

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 an...

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Main Authors: Niu, Yiming, Bai, Jing, Wang, Yitao, Wang, Chunming, Kamm, Roger Dale
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: American Chemical Society (ACS) 2015
Online Access:http://hdl.handle.net/1721.1/97868
https://orcid.org/0000-0002-7232-304X
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author Niu, Yiming
Bai, Jing
Wang, Yitao
Wang, Chunming
Kamm, Roger Dale
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Niu, Yiming
Bai, Jing
Wang, Yitao
Wang, Chunming
Kamm, Roger Dale
author_sort Niu, Yiming
collection MIT
description 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.
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spelling mit-1721.1/978682022-09-26T11:16:45Z Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment Niu, Yiming Bai, Jing Wang, Yitao Wang, Chunming Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Bai, Jing Kamm, Roger Dale 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. 2015-07-21T12:41:59Z 2015-07-21T12:41:59Z 2014-02 2014-02 Article http://purl.org/eprint/type/JournalArticle 1543-8384 1543-8392 http://hdl.handle.net/1721.1/97868 Niu, Yiming, Jing Bai, Roger D. Kamm, Yitao Wang, and Chunming Wang. “Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment.” Mol. Pharmaceutics 11, no. 7 (July 7, 2014): 2022–2029. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1021/mp500054h Molecular Pharmaceutics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC
spellingShingle Niu, Yiming
Bai, Jing
Wang, Yitao
Wang, Chunming
Kamm, Roger Dale
Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title_full Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title_fullStr Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title_full_unstemmed Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title_short Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
title_sort validating antimetastatic effects of natural products in an engineered microfluidic platform mimicking tumor microenvironment
url http://hdl.handle.net/1721.1/97868
https://orcid.org/0000-0002-7232-304X
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