Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models
Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo respo...
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doaj-169f5e6be4f049de9298ed6a1cdf4dff2020-11-24T21:54:16ZengMDPI AGMolecules1420-30492016-07-0121795410.3390/molecules21070954molecules21070954Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor ModelsHui Guo0Dongmei Liu1Bin Gao2Xiaohui Zhang3Minli You4Hui Ren5Hongbo Zhang6Hélder A. Santos7Feng Xu8Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaDepartment of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaDivision of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, FinlandDivision of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, FinlandThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaEvodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.http://www.mdpi.com/1420-3049/21/7/954cellular uptakeauto-fluorescence3D multicellular spheroidshanging drop method |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Guo Dongmei Liu Bin Gao Xiaohui Zhang Minli You Hui Ren Hongbo Zhang Hélder A. Santos Feng Xu |
spellingShingle |
Hui Guo Dongmei Liu Bin Gao Xiaohui Zhang Minli You Hui Ren Hongbo Zhang Hélder A. Santos Feng Xu Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models Molecules cellular uptake auto-fluorescence 3D multicellular spheroids hanging drop method |
author_facet |
Hui Guo Dongmei Liu Bin Gao Xiaohui Zhang Minli You Hui Ren Hongbo Zhang Hélder A. Santos Feng Xu |
author_sort |
Hui Guo |
title |
Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models |
title_short |
Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models |
title_full |
Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models |
title_fullStr |
Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models |
title_full_unstemmed |
Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models |
title_sort |
antiproliferative activity and cellular uptake of evodiamine and rutaecarpine based on 3d tumor models |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2016-07-01 |
description |
Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds. |
topic |
cellular uptake auto-fluorescence 3D multicellular spheroids hanging drop method |
url |
http://www.mdpi.com/1420-3049/21/7/954 |
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