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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

Ellen Friday1, Johnathan Ledet, Francesco Turturro

  • 1Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA. fturturro@mdanderson.org

Journal of Experimental & Clinical Cancer Research : CR
|September 14, 2011
PubMed
Abstract

Insights

High glucose or dexamethasone (DEX) impacts thioredoxin-interacting protein (TXNIP) and reactive oxygen species (ROS) in multiple myeloma (MM) cells. Glucose modulates DEX efficacy by regulating ROS, suggesting metabolic factors influence MM treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Metabolic Regulation

Background:

  • Hyperglycemia is a significant side effect of dexamethasone (DEX) treatment.
  • Glucose and glucocorticoids (GCs) regulate thioredoxin-interacting protein (TXNIP), a key mediator of reactive oxygen species (ROS) production via thioredoxin (TRX) activity.

Purpose of the Study:

  • To investigate how glucose and DEX influence TXNIP expression and ROS production in multiple myeloma (MM) cells.
  • To determine if glucose modulates DEX efficacy and toxicity in MM cells.

Main Methods:

  • Multiple myeloma cells were cultured under varying glucose concentrations (5 or 20 mM/L) with or without DEX (25 μM).
  • TXNIP RNA expression was assessed using RT-PCR.
  • ROS levels, TRX activity, and cell proliferation were measured to determine DEX IC50.

Main Results:

  • Both glucose and DEX modulated TXNIP RNA levels in a cell-dependent manner.
  • Increased ROS levels correlated with reduced TRX activity, except in MC/CAR cells where glucose enhanced TRX activity.
  • Glucose significantly reduced ROS levels when combined with DEX in certain MM cell lines (ARH77/NCIH9292), and increased DEX IC50 tenfold in ARH77 and MC/Car cells.

Conclusions:

  • Glucose and DEX regulate ROS production in MM cells via TXNIP modulation or direct interference with TRX activity.
  • Glucose modulates DEX activity by influencing ROS levels in MM cells, impacting drug efficacy and potentially toxicity.
  • Understanding the metabolic milieu's role is crucial for optimizing DEX treatment in diabetic and non-diabetic MM patients.

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