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Updated: Jul 25, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Apaf-1/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells

D Chauhan1, T Hideshima, S Rosen

  • 1Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

The Journal of Biological Chemistry
|May 18, 2001
PubMed

Insights

Smac (second mitochondria-derived activator of caspases) release mediates dexamethasone-induced apoptosis in multiple myeloma cells by activating caspase-9. Interleukin-6 blocks this Smac-dependent pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Smac (second mitochondria-derived activator of caspases) is crucial for caspase activation.
  • Dexamethasone (Dex) is a therapeutic agent used in multiple myeloma (MM).
  • Interleukin-6 (IL-6) is a key growth factor for MM cells.

Purpose of the Study:

  • To investigate the role of Smac in dexamethasone-induced apoptosis in MM cells.
  • To elucidate the mechanism of caspase-9 activation by Smac in MM.
  • To determine the effect of IL-6 on Smac release and apoptosis in MM.

Main Methods:

  • Treatment of MM cells with dexamethasone.
  • Mitochondrial and cytosolic fractionation to assess Smac localization.
  • Caspase activity assays.
  • Western blotting to detect protein oligomerization and interactions.

Main Results:

  • Dexamethasone treatment induced Smac release from mitochondria to the cytosol in MM cells.
  • Caspase-9 activation occurred independently of cytochrome c release and Apaf-1 oligomerization.
  • Smac binding to XIAP (inhibitor of apoptosis protein) reduced XIAP's inhibition of caspase-9.
  • Interleukin-6 inhibited dexamethasone-induced apoptosis by preventing Smac release.

Conclusions:

  • Smac is a key mediator of dexamethasone-induced apoptosis in multiple myeloma cells.
  • Smac facilitates caspase-9 activation through XIAP inhibition, independent of the canonical mitochondrial pathway.
  • Interleukin-6 confers resistance to dexamethasone by blocking Smac release, highlighting a potential therapeutic target.

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