Salidroside Induces Apoptosis in Human Gastric Cancer Cells via the Downregulation of ENO1/PKM2/GLUT1 Expression

Biol Pharm Bull. 2021 Nov 1;44(11):1724-1731. doi: 10.1248/bpb.b21-00443. Epub 2021 Sep 2.

Abstract

Salidroside is reported to have a wide range of pharmacological properties and has been proven to play a key anti-cancer effect. This study investigated the effects of purified salidroside, an ingredient of Rhodiola rosea, on the proliferation of two human gastric cancer cell lines and further investigating its possible molecular mechanisms. We verified that salidroside exerts a dose-dependent inhibitory effect on the proliferation of SGC-7901 and MKN-45 human gastric cancer cells. Moreover, salidroside can induce cell apoptosis, which was accompanied by an increase in nuclear fragmentation. In addition, salidroside inhibited glycolysis, as evidenced by the reduced expression levels of the glycolysis-related enzymes pyruvate kinase isoenzyme M2 (PKM2), enolase 1 (ENO1) and glucose transporter 1 (GLUT1), which could play important roles in the metabolism of gastric cancer cells. Further investigation showed that salidroside exerted potent anti-proliferative effects by inhibiting glycolysis in human gastric cancer cells in vitro. In vivo, xenograft tumors treated with salidroside were significantly smaller than those in the control animals. Therefore, salidroside could be a promising therapeutic prospect in the treatment of gastric cancer.

Keywords: enolase 1 (ENO1); gastric cancer; glucose transporter 1 (GLUT1); glycolysis; pyruvate kinase isoenzyme M2 (PKM2); salidroside.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Glucose Transporter Type 1 / metabolism*
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Glycolysis / drug effects
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phenols / pharmacology*
  • Phenols / therapeutic use
  • Phosphopyruvate Hydratase / metabolism*
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rhodiola / chemistry*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Carrier Proteins
  • DNA-Binding Proteins
  • Glucose Transporter Type 1
  • Glucosides
  • Membrane Proteins
  • Phenols
  • Plant Extracts
  • SLC2A1 protein, human
  • Thyroid Hormones
  • Tumor Suppressor Proteins
  • ENO1 protein, human
  • Phosphopyruvate Hydratase
  • rhodioloside