Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models.

Hui Guo,Hui Ren,Dongmei Liu,Minli You,Feng Xu,Hongbo Zhang,Hélder Santos,Xiaohui Zhang,Bin Gao

doi:10.3390/molecules21070954

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.

Highlights

Evodia rutaecarpa (Chinese name: Wu-Chu-Yu), a traditional Chinese herb, has been widely used for treating various diseases for thousands of years [1]
Fabrication and Characterization of 3D Tumor Spheroids evaluate the cellular uptake of EVO and RUT in MCF-7 and SMMC-7721 cancer cells
The IC50 of MCF-7 and SMMC-7721 cells in 2D for all three drugs was in the range of 6.4–44.1 μM, while the IC50 of the MCF-7 and SMMC-7721 cell spheroids were much higher (21.8–138.0 μM), which may be due to enhanced mass barrier and reduced drug penetration in 3D models

Summary

Introduction

Evodia rutaecarpa (Chinese name: Wu-Chu-Yu), a traditional Chinese herb, has been widely used for treating various diseases (e.g., gastrointestinal disorders, amenorrhea, headache, and postpartum hemorrhage) for thousands of years [1]. Molecules 2016, 21, 954 including anti-inflammatory [3], anti-obesity [4] and anti-tumor effects [5,6,7,8,9,10], has been well studied. It 954 has been reported that EVO has anti-tumor potential by inhibiting cell proliferation and Molecules. It is of great importance to including anti-inflammatory anti-obesity [4] and further study the anti-tumor [3], effects of EVO and RUT.anti-tumor effects [5,6,7,8,9,10], has been well studied

Objectives

Methods

Results

Conclusion