title: Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models.
abstract: 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.
authors.affiliation: Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China. guohui20032476@163.com.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. guohui20032476@163.com.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. guohui20032476@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China. liudongmei201605@163.com.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. liudongmei201605@163.com.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. liudongmei201605@163.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. bingao0726@163.com.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. bingao0726@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. xiaohuizhang@mail.xjtu.edu.cn.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. xiaohuizhang@mail.xjtu.edu.cn.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. knightminli@gmail.com.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. knightminli@gmail.com.
authors.forename: Minli
authors.initials: M
authors.lastname: You
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. jessie_renhui@aliyun.com.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. jessie_renhui@aliyun.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland. hongbo.zhang@helsinki.fi.|School of Engineering and Applied Physics, Harvard University, Cambridge, MA 02138, USA. hongbo.zhang@helsinki.fi.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland. helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. fengxu@mail.xjtu.edu.cn.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China. fengxu@mail.xjtu.edu.cn.|Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710049, China. fengxu@mail.xjtu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013057:Spectrum Analysis; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D052999:Quinazolinones
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D010936:Plant Extracts; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine
keywords: 3D multicellular spheroids; auto-fluorescence; cellular uptake; hanging drop method