Erufosine simultaneously induces apoptosis and autophagy by modulating the Akt-mTOR signaling pathway in oral squamous cell carcinoma

Cancer Lett. 2012 Jun 1;319(1):39-48. doi: 10.1016/j.canlet.2011.12.032. Epub 2011 Dec 24.

Abstract

We investigated the anticancer activity of erufosine in oral squamous carcinoma cell lines in terms of cell proliferation, colony formation, induction of autophagy/apoptosis, cell cycle and mTOR signaling pathway. Erufosine showed dose-dependent cytotoxicity in all cell lines, it induced autophagy as well as apoptosis, G2 cell cycle arrest and modulation of cyclin D1 expression. Further erufosine downregulated the phosphorylation of major components of mTOR pathway, like p-Akt at Ser473 and Thr308 residues, p-Raptor, p-mTOR, p-PRAS40 and its downstream substrates p-p70S6K and p-4EBP1 in a dose-dependent manner. The pre-treatment of tumor cells with p-mTOR siRNA increased cytotoxic effects of erufosine comparable to cisplatin but higher than rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Organophosphates / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quaternary Ammonium Compounds / pharmacology*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Organophosphates
  • Quaternary Ammonium Compounds
  • erucylphospho-N,N,N-trimethylpropylammonium
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt