Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

Biochem Biophys Res Commun. 2014 Mar 28;446(1):105-12. doi: 10.1016/j.bbrc.2014.02.043. Epub 2014 Feb 28.

Abstract

Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

Keywords: Autophagy; Gastric cancer; Proliferation inhibition; Tigecycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Mice
  • Mice, SCID
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • TOR Serine-Threonine Kinases / metabolism
  • Tigecycline
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Tigecycline
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa
  • AMP-Activated Protein Kinases
  • Minocycline