Related Experiment Video

Updated: Jul 2, 2026

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
10:04

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis

Published on: May 1, 2015

Growth control of multiple myeloma cells through inhibition of glycogen synthase kinase-3

Ying Zhou1, Shahab Uddin, Todd Zimmerman

  • 1Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Leukemia & Lymphoma
|August 30, 2008
PubMed

Insights

Glycogen synthase kinase-3 (GSK3) inhibition by TDZD effectively reduced multiple myeloma cell growth and induced apoptosis. This GSK3 inhibitor protected normal cells while targeting cancer cells, showing potential for clinical use.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Anti-apoptotic pathways are crucial for multiple myeloma cell survival.
  • The roles of PI3-kinase and Akt kinase in myeloma cell survival are established, but glycogen synthase kinase-3 (GSK3) involvement is less defined.

Purpose of the Study:

  • To investigate the contribution of GSK3 in the growth regulation of multiple myeloma cells.
  • To evaluate the effects of a GSK3 inhibitor on myeloma cell proliferation and apoptosis.

Main Methods:

  • Six multiple myeloma cell lines and primary myeloma cells were treated with Thiadiazolidinone (TDZD), a GSK3 inhibitor.
  • Proliferation, apoptosis, and forkhead transcription factor (FOXO) activation were assessed.
  • Effects on normal hematopoietic cells were also evaluated.

Main Results:

  • TDZD inhibited proliferation and induced apoptosis in all tested myeloma cell lines and primary cells.
  • Normal hematopoietic cells were protected from TDZD-induced apoptosis.
  • GSK3 inhibition led to FOXO3a dephosphorylation and activation.
  • Pro-apoptotic proteins Fas ligand (FasL) and IkappaBalpha increased post-TDZD treatment.

Conclusions:

  • GSK3 plays a significant role in multiple myeloma cell growth regulation.
  • TDZD demonstrates selective toxicity towards myeloma cells, sparing normal hematopoietic cells.
  • GSK3 inhibitors like TDZD represent a promising therapeutic strategy for multiple myeloma.

More Related Videos

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice05:32

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

Published on: January 7, 2019

Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos07:24

Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos

Published on: December 13, 2018

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.