Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits bladder cancer cell growth via the mitochondrial apoptosis and JNK pathways

Toxicol Appl Pharmacol. 2019 May 15:371:41-54. doi: 10.1016/j.taap.2019.03.027. Epub 2019 Apr 1.

Abstract

Erianin, a component extracted from the traditional Chinese herbal medicine Dendrobium, has shown significant anti-tumour activity in various cancers but not in bladder cancer. In this study, we assessed the effects of Erianin on bladder cancer growth and elucidated the related mechanisms. First, Erianin was synthesized with high yields, and markedly suppressed EJ and T24 cell proliferation. It induced G2/M-phase arrest in vitro. Furthermore, Erianin triggered apoptosis via caspase cascades activation and the mitochondrial-mediated apoptotic pathway. Bim up-regulation and Bcl-2 down-regulation as the symbol of apoptosis which were found to play the dominant role in the effects of Erianin. We further showed that JNK pathway activation is necessary for the Erianin-mediated anti-proliferation and apoptotic response. Finally, Erianin exhibited anti-tumour activity and induced apoptosis in tumour tissue in vivo. Collectively, these results suggest that Erianin induced cell cycle G2/M-phase arrest and apoptosis via the JNK signalling pathway in bladder cancer, indicating the potential usefulness of Erianin for the therapy of bladder cancer.

Keywords: Apoptosis; Bladder cancer; Erianin; In vivo; JNK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Bcl-2-Like Protein 11 / genetics
  • Bcl-2-Like Protein 11 / metabolism
  • Bibenzyls / isolation & purification
  • Bibenzyls / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dendrobium* / chemistry
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mice, Nude
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Mitochondria / pathology
  • Phenol
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Tumor Burden / drug effects
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Bibenzyls
  • Erianin
  • Proto-Oncogene Proteins c-bcl-2
  • Phenol
  • JNK Mitogen-Activated Protein Kinases