Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis

Leuk Res. 2010 Nov;34(11):1533-8. doi: 10.1016/j.leukres.2010.07.002. Epub 2010 Jul 27.


The Hsp90 inhibitor 17DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) is currently undergoing clinical trials as an antitumor drug. We show here that treatment of human multiple myeloma (MM) cells with 17DMAG induces mTOR inhibition and microtubule-associated protein light chain 3 (LC3) conversion (LC3-I to LC3-II), an indicator of autophagy. Interestingly, 17DMAG synergistically induces apoptosis through a mitochondria-operated pathway in the presence of the autophagy inhibitor 3-methyladenine (3-MA). Inhibition of autophagy by 3-MA facilitated caspase activation, cytochrome c release from mitochondria and poly (ADP-ribose) polymerase (PARP) cleavage in myeloma cells treated with 17DMAG. The potential use of Hsp90 and autophagy inhibitors combinations as a therapeutic tool in MM is further discussed in our work.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Benzoquinones / pharmacology*
  • Benzoquinones / therapeutic use
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Humans
  • Lactams, Macrocyclic / pharmacology*
  • Lactams, Macrocyclic / therapeutic use
  • Mitochondria / metabolism
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology


  • Antineoplastic Agents
  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
  • 3-methyladenine
  • Adenine