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[Mechanisms of arsenic trioxide-induced apoptosis in myeloma cells]

Y Zhou1, X Huang, X Cai

  • 1Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]
|January 11, 2002
PubMed
Abstract

Insights

Arsenic trioxide (As2O3) induces apoptosis in multiple myeloma (MM) cells via sulfhydryl groups. All-trans retinoic acid (ATRA) and interferon-alpha (IFN-alpha) do not enhance As2O3

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) is a hematological malignancy.
  • Understanding the mechanisms of apoptosis induction is crucial for developing novel therapies.
  • Arsenic trioxide (As2O3) has shown anti-cancer properties.

Purpose of the Study:

  • To elucidate the mechanisms of As2O3-induced apoptosis in MM cells.
  • To investigate the synergistic potential of As2O3 with all-trans retinoic acid (ATRA) and interferon-alpha (IFN-alpha).

Main Methods:

  • MM cell lines (RPMI 8226, U266) were treated with As2O3, dithiothreitol (DTT), buthionine sulfoximine (BSO), ATRA, and IFN-alpha.
  • Cell viability was assessed using trypan-blue exclusion.
  • Apoptosis and mitochondrial transmembrane potentials (Δψm) were measured by flow cytometry.

Main Results:

  • Buthionine sulfoximine (BSO) enhanced As2O3-induced apoptosis, while dithiothreitol (DTT) partially antagonized it, suggesting the involvement of sulfhydryl groups.
  • ATRA induced apoptosis in RPMI 8226 cells but did not synergize with As2O3.
  • As2O3-induced apoptosis was observed in RPMI 8226 cells but not in U266 cells.
  • IFN-alpha did not affect MM cell viability or the efficacy of As2O3.

Conclusions:

  • As2O3-induced apoptosis in RPMI 8226 MM cells is mediated by sulfhydryl groups.
  • ATRA and IFN-alpha do not exhibit synergistic effects with As2O3 in inducing apoptosis in MM cells.

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