A plant molecule has been purified in our lab. The molecule is showing antioxidant property in blood components at 100µM after inducing stress by known oxidant (DNP), hemolysis occured as the concentration of plant molecule increased. The same molecule at same concentration induces apoptosis in breast cancer via ROS mediated mitochondrial damage. How can a single molecule acts as an antioxidant in RBCs and pro-oxidant in cancer cells? What is the mechanism of action?
I think that the lack of a nucleus in RBCs has somethingto do withthe difference.
This phenomenon may depend upon a lot of parameters. For example, it's well known fact that the extracellular microenvironment of malignant cells is acidified (for breast cancer, the difference is approximately 0.35 pH units). Possible, your substance has highly pH-sensitive redox potential or ROS-scavenging ability. Similar behavior is observed for the ceria nanoparticles, see the attached paper, figs.3-5.
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The shifting of surrounding environmental measurements affect the biochemical pathway of different molecules and can switch their pattern of reaction. pH, Temperature, aggregation of other molecules and many other factors can implement this changes.
Thank you for all your answers. I kind of thought of the same reason which Dr. Koltai suggested. Dr. Shcherbakov and Dr. Mohammed, you both are probably suggesting more or less the same reason? But all my experiments were done in vitro using neutral pH medium on cell lines. Another molecule with similar effect is Quercetin, which is shown to induce ROS mediated apoptosis in cancer cell lines and is a well known antioxidant. How can this be explained?
The question about pro- and antioxidant activity of substances is quite complicated and it is difficult to explain the issue in one or two sentences. The main thesis: this depends on the mechanisms and processes in which the substance is involved. For example, carotenoids are free radical scavengers and can act as antioxidant in such type of reactions (peroxidation of lipids or fats), but they have high redox-potential (up to 700 mV vs SCE) and can act as a direct oxidant in some systems. Ascorbic acid is a conventional antioxidant per se, but it can work as a strong pro-oxidant in the presence of transition metal ions due to participation in Fenton’s reaction and producing of hydroxyl or superoxide radicals. Polyphenols (quercetin) like an ascorbic acid possess the direct antioxidant activity and can quench free-radical processes (for example, lipid peroxidation of RBC’s membranes), while they can be auto-oxidized even at physiological pH and promote hydroxyl radical generation (Fenton process) too. Moreover, oxidative conditions of the aerobic glycolysis of cancer cell can cause quercetin’s transformation into highly reactive quinone species, etc.
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