Caspase-independent apoptosis induction of quorum-sensing autoinducer analogs against chronic myeloid leukemia K562

Invest New Drugs. 2012 Jun;30(3):862-9. doi: 10.1007/s10637-010-9623-z. Epub 2011 Jan 5.

Abstract

Quorum sensing is defined as the ability of microorganisms to sense their population density via the release of signaling molecules called autoinducers (AIs). Various types of AI analogs were prepared and their antitumor properties against chronic myeloid leukemia (CML) K562 cells were investigated. Two AI analogs induced progressive apoptosis with JNK activation and p21 induction. In addition, this induction of apoptosis is not related to bcr-abl kinase, which sustains CML proliferation. However, the progression of apoptosis was not inhibited by a caspase family inhibitor. These results suggested that AI analogs could induce caspase-independent apoptosis in CML K562.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cysteine Proteinase Inhibitors / pharmacology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • K562 Cells
  • Lactones / pharmacology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Quorum Sensing / physiology*
  • p21-Activated Kinases / metabolism

Substances

  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Lactones
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • p21-Activated Kinases
  • JNK Mitogen-Activated Protein Kinases