N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo

Int J Mol Sci. 2020 Aug 13;21(16):5815. doi: 10.3390/ijms21165815.

Abstract

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.

Keywords: N6-(2-Hydroxyethyl)-adenosine; apoptosis; autophagy; endoplasmic reticulum stress; gastric carcinoma.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • HEK293 Cells
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Nude
  • Reactive Oxygen Species / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / ultrastructure

Substances

  • N6-(2-hydroxyethyl)adenosine
  • Reactive Oxygen Species
  • Adenosine
  • Calcium