Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour Models

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

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Article number954
JournalMolecules
Volume21
Issue number7
Pages (from-to)954
Number of pages13
ISSN1420-3049
DOIs
Publication statusPublished - 21 Jul 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • 116 Chemical sciences
  • cellular uptake
  • auto-fluorescence
  • 3D multicellular spheroids
  • hanging drop method
  • IN-VITRO
  • BREAST-CANCER
  • DRUG DISCOVERY
  • CELLS
  • CAMPTOTHECIN
  • DERIVATIVES
  • APOPTOSIS
  • LINES
  • TRANSFORMATION
  • MECHANISM

Cite this

Guo, Hui ; Liu , Dongmei ; Gao , Bin ; Zhang, Xiaohui ; You, Minli ; Ren, Hui ; Zhang, Hongbo ; Almeida Santos, Helder ; Xu , Feng . / Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour Models. In: Molecules. 2016 ; Vol. 21, No. 7. pp. 954.
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title = "Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour 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.",
keywords = "317 Pharmacy, 116 Chemical sciences, cellular uptake , auto-fluorescence , 3D multicellular spheroids , hanging drop method , IN-VITRO , BREAST-CANCER , DRUG DISCOVERY , CELLS , CAMPTOTHECIN , DERIVATIVES , APOPTOSIS , LINES , TRANSFORMATION , MECHANISM",
author = "Hui Guo and Dongmei Liu and Bin Gao and Xiaohui Zhang and Minli You and Hui Ren and Hongbo Zhang and {Almeida Santos}, Helder and Feng Xu",
year = "2016",
month = "7",
day = "21",
doi = "10.3390/molecules21070954",
language = "English",
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pages = "954",
journal = "Molecules",
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Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour Models. / Guo, Hui ; Liu , Dongmei ; Gao , Bin ; Zhang, Xiaohui ; You, Minli ; Ren, Hui ; Zhang, Hongbo; Almeida Santos, Helder; Xu , Feng .

In: Molecules, Vol. 21, No. 7, 954, 21.07.2016, p. 954.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour Models

AU - Guo, Hui

AU - Liu , Dongmei

AU - Gao , Bin

AU - Zhang, Xiaohui

AU - You, Minli

AU - Ren, Hui

AU - Zhang, Hongbo

AU - Almeida Santos, Helder

AU - Xu , Feng

PY - 2016/7/21

Y1 - 2016/7/21

N2 - 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.

AB - 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.

KW - 317 Pharmacy

KW - 116 Chemical sciences

KW - cellular uptake

KW - auto-fluorescence

KW - 3D multicellular spheroids

KW - hanging drop method

KW - IN-VITRO

KW - BREAST-CANCER

KW - DRUG DISCOVERY

KW - CELLS

KW - CAMPTOTHECIN

KW - DERIVATIVES

KW - APOPTOSIS

KW - LINES

KW - TRANSFORMATION

KW - MECHANISM

UR - http://www.mdpi.com/journal/molecules

U2 - 10.3390/molecules21070954

DO - 10.3390/molecules21070954

M3 - Article

VL - 21

SP - 954

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 7

M1 - 954

ER -