Small compound bigelovin exerts inhibitory effects and triggers proteolysis of E2F1 in multiple myeloma cells

Cancer Sci. 2013 Dec;104(12):1697-704. doi: 10.1111/cas.12295. Epub 2013 Nov 8.

Abstract

Multiple myeloma (MM) is a currently incurable blood cancer. Here we tested the effects of a small compound bigelovin on MM cells, and reported that it caused cell cycle arrest and subsequently induced apoptosis. Bigelovin triggered proteolysis of E2F1, which could be inhibited by caspase inhibitor. To investigate the clinical relevance, the expression of E2F1 in MM specimens was tested, and the results showed that E2F1 was overexpressed in 25-57% of MM patients and was associated with higher International Staging System (ISS) stage. These results suggest that E2F1 may be important for MM pathogenesis, and bigelovin could serve as a lead compound for the development of E2F1 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / drug effects
  • Caspase Inhibitors / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival
  • Down-Regulation
  • E2F1 Transcription Factor / metabolism*
  • Female
  • Humans
  • Lactones / pharmacology*
  • Male
  • Mice
  • Multiple Myeloma / metabolism*
  • Proteolysis / drug effects*
  • RNA Interference
  • RNA, Small Interfering
  • Sesquiterpenes / pharmacology*

Substances

  • Caspase Inhibitors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Lactones
  • RNA, Small Interfering
  • Sesquiterpenes
  • bigelovin