Role of Oxidative Stress in Killing of Cancer Cells

It is known that normal cells and cancer cells differ in their ability to obtain energy from oxidative metabolism. Whereas normal cells obtain more than 95% of their energy from mitochondrial respiration and only a small amount of energy from glycolysis, cancer cells are believed to have a defect in mitochondrial respiration resulting in their dependence on glycolysis to provide much of their energy needs. Mitochondrial respiration also produces reactive oxygen species (ROS) which are toxic to cells, and agents that affect mitochondrial respiration or cause excess ROS production could be especially harmful to cancer cells.

Sulindac in Combination with Oxidative Stress (Peroxide) has an Enhanced and Selective Anti-Cancer Effect.

Dr. Herbert Weissbach, Director of the Center for Molecular Biology and Biotechnology at Florida Atlantic University, and colleagues have discovered that sulindac, our lead candidate, can sensitize cancer cells to oxidative stress. Sulindac is an FDA-approved drug (marketed as Clinoril™ by Merck) that has been widely used in patients with arthritis since the 1970s. Unexpectedly, about 15 years ago, it was found to also have anti-cancer effects. Our research shows that the combination of sulindac and an oxidizing agent, such as hydrogen peroxide, will act synergistically and selectively to target and kill cancer cells while exhibiting a protective effect on some normal cells. This effect occurs at concentrations of sulindac and hydrogen peroxide that individually have little or no activity directed against cancer cells.


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