Evaluation of anti-tumor effects of crocin on a novel 3D tissue-engineered tumor model based on sodium alginate/gelatin microbead

Int J Biol Macromol. 2021 Mar 31:174:339-351. doi: 10.1016/j.ijbiomac.2021.01.181. Epub 2021 Jan 30.

Abstract

Crocin, as one of the biologically active components of saffron, has anti-inflammatory, anti-oxidant, anti-depressant and auxiliary anti-tumor effects. Studies have shown that crocin could promote breast cancer cell apoptosis. However, conventional methods are mainly based on two-dimensional (2D) cell culture models, which are difficult to reproduce the tumor environment in vivo due to space constraints. In this study, we prepared a three-dimensional (3D) cell model in vitro based on sodium alginate/gelatin to evaluate the inhibitory effect of crocin on MCF-7 cells, which could bridge the gap in crocin drug evaluation between 2D and 3D cell model in vitro. Different from the 2D culture, the cells were found to aggregate in a spherical shape in the 3D microgel beads. And the CCK-8 assay showed that the growth of MCF-7 cells exposed to crocin was inhibited in a time-related and concentration-related manner. Compared with 2D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 3.68, 2.55 and 1.53 mg/mL, respectively), the IC50 value of 3D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 10.12, 6.89 and 6.64 mg/mL, respectively) was significantly increased by 2.77, 2.70, 4.34 times, respectively. Besides, live/dead staining and scanning electron microscope (SEM) revealed that the 2D cultured cells shrank and ruptured after crocin treatment, and the number of living cells was considerably reduced; the size of the cell colonies in the 3D microgel beads decreased.

Keywords: Anti-tumor; Crocin; Three-dimensional cell model.

MeSH terms

  • 3T3 Cells
  • Alginates / chemistry*
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carotenoids / chemistry
  • Carotenoids / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gelatin / chemistry*
  • Humans
  • MCF-7 Cells
  • Mice
  • Microspheres
  • Models, Biological
  • Time Factors
  • Tumor Microenvironment / drug effects

Substances

  • Alginates
  • Antineoplastic Agents, Phytogenic
  • Carotenoids
  • crocin
  • Gelatin