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Arsenic trioxide sensitivity is associated with low level of glutathione in cancer cells

C H Yang1, M L Kuo, J C Chen

  • 1Department of Oncology, Graduate Institute of Medicine, National Taiwan University Hospital and Medical College, National Taiwan University, Taipei.

British Journal of Cancer
|November 11, 1999
PubMed

Insights

Arsenic trioxide shows promise as an anticancer agent, particularly for bladder, acute promyelocytic leukemia, and gastrointestinal cancers. Cellular glutathione levels are key to arsenic sensitivity, with lower levels indicating higher sensitivity.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Arsenic trioxide (As2O3) is an emerging anticancer therapeutic.
  • Its efficacy in various cancers beyond acute promyelocytic leukemia requires further investigation.
  • The role of cellular detoxification mechanisms in arsenic response is not fully understood.

Purpose of the Study:

  • To evaluate the cytotoxic effects of arsenic trioxide across a broad range of cancer cell lines.
  • To determine the relationship between cellular glutathione (GSH) levels and sensitivity to arsenic trioxide.
  • To explore the potential of modulating GSH levels to enhance arsenic-induced cancer cell death.

Main Methods:

  • Cytotoxicity assays were performed on 17 different cancer cell lines treated with arsenic trioxide.
  • Cellular glutathione (GSH) levels were measured in sensitive and resistant cell lines.
  • The impact of L-buthionine sulphoximine, a GSH-depleting agent, on arsenic sensitivity was assessed.

Main Results:

  • Bladder, acute promyelocytic leukemia, and gastrointestinal cancer cells exhibited the highest sensitivity to arsenic trioxide.
  • Intrinsically sensitive cancer cells had lower endogenous GSH levels compared to resistant cells.
  • Depletion of cellular GSH using L-buthionine sulphoximine significantly increased cancer cell sensitivity to arsenic trioxide.

Conclusions:

  • Cellular glutathione level is a critical determinant of arsenic trioxide sensitivity in cancer cells.
  • Modulating GSH levels, potentially with agents like buthionine sulphoximine, could be a strategy to enhance arsenic therapy in solid tumors.
  • Further research into GSH's role is warranted for optimizing arsenic-based cancer treatments.

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