Chrysophanol Suppresses Hypoxia-Induced Epithelial-Mesenchymal Transition in Colorectal Cancer Cells

Anat Rec (Hoboken). 2019 Sep;302(9):1561-1570. doi: 10.1002/ar.24081. Epub 2019 Feb 27.

Abstract

Colorectal cancer (CRC) is a common human malignancy, accounting for 600,000 death cases annually worldwide. Chrysophanol is a naturally occurring anthraquinone compound and exhibits anti-neoplastic activities. This study aims to explore the biological effects of chrysophanol on CRC metastasis and the relevant underlying mechanism. Cell proliferation assay, wound scratch assay, and Transwell invasion assay were used to examine the effect of chrysophanol on proliferation, migration, and invasion of CRC cells. Hypoxia-inducible factor-1α (HIF-1α) shRNA was utilized to transfect CRC cells to examine the role of HIF-1α in chrysophanol suppression of hypoxia-induced epithelial to mesenchymal transition (EMT). The suppression effect of chrysophanol on hypoxia-induced EMT in vivo was also validated in xenograft tumor models. In the present study, our findings indicated that chrysophanol has the capability to suppress hypoxia-induced EMT in CRC in vitro and in vivo, and the possible mechanism involved is the inhibition of HIF-1α via modulating PI3k/Akt signaling pathway. Collectively, the results indicated that chrysophanol can be used as an EMT and cancer metastasis inhibitor in the treatment of CRC. Anat Rec, 302:1561-1570, 2019. © 2019 American Association for Anatomy.

Keywords: EMT; HIF-1α; chrysophanol; colorectal cancer; hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Anthraquinones / pharmacology*
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Hypoxia / physiopathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutagens / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anthraquinones
  • Mutagens
  • chrysophanic acid