Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity

We have previously demonstrated that certain agents generating reactive oxygen species such as 2-methoxyestradiol preferentially kill human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes

Elizabeth Oldham Hileman; Jinsong Liu; Maher Albitar; Michael J. Keating; Peng Huang

2004

Scholarcy highlights

  • Therapeutic selectivity is one of the most important considerations in cancer chemotherapy
  • MTT assays were used as indicators of cellular viability
  • Western blot analysis was used to measure the expression of antioxidant enzymes in cancer and normal cells
  • Malignant cells in general are more active than normal cells in the production of O2−, are under intrinsic oxidative stress, and are more vulnerable to damage by reactive oxygen species-generating agents
  • The intrinsic oxidative stress in cancer cells was associated with the upregulation of SOD and catalase protein expression, likely as a mechanism to tolerate increased ROS stress
  • O2− is an important mediator of 2-ME-induced apoptosis
  • The increased oxidative stress in cancer cells forces these cells to rely more on antioxidant enzymes such as SOD for O2− elimination, making the malignant cells more vulnerable to SOD inhibition than normal cells

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