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Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties
S M Hadi1, Showket H Bhat, Asfar S Azmi
1Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002, UP, India. smhadi@vsnl.com
Abstract:
Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. We have shown that several of these compounds are able to bind both DNA and Cu(II) forming a ternary complex. A redox reaction of the polyphenols and Cu(II) in the ternary complex may occur leading to the reduction of Cu(II) to Cu(I), whose reoxidation generates a variety of reactive oxygen species (ROS). We have further confirmed that the polyphenol-Cu(II) system is indeed capable of causing DNA degradation in cells such as lymphocytes. We have also shown that polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. Neocuproine (a Cu(I) sequestering agent) inhibits such DNA degradation. It also inhibits the oxidative stress generated in lymphocytes indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and polyphenols to generate ROS. Thus, our results are in support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper possibly chromatin bound copper and the consequent prooxidant action.
Insights
Plant polyphenols can act as antioxidants or prooxidants, causing DNA damage by interacting with copper ions. This prooxidant action, involving reactive oxygen species, may explain their anticancer effects by targeting cancer cells with elevated copper levels.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Plant polyphenols are dietary compounds with recognized chemopreventive and therapeutic potential against cancer.
- While known as antioxidants, polyphenols can also act as prooxidants, catalyzing DNA degradation, particularly with transition metal ions like copper.
Purpose of the Study:
- To investigate the mechanism by which plant polyphenols induce DNA damage.
- To explore the role of copper ions and reactive oxygen species (ROS) in polyphenol-induced DNA breakage.
- To test the hypothesis that the anticancer mechanism of polyphenols involves copper mobilization and prooxidant activity.
Main Methods:
- Formation and characterization of ternary complexes between plant polyphenols, Cu(II), and DNA.
- Assessment of DNA degradation in lymphocytes exposed to polyphenol-Cu(II) systems.
- Evaluation of the effect of neocuproine (a Cu(I) sequestering agent) on DNA damage and oxidative stress.
- Correlation of findings with known elevated copper levels in malignancies.
Main Results:
- Plant polyphenols bind to both DNA and Cu(II), forming ternary complexes.
- The polyphenol-Cu(II) system induces DNA degradation in lymphocytes, generating reactive oxygen species (ROS).
- Polyphenols alone can cause DNA breakage in cells, and this process is inhibited by neocuproine, indicating a role for Cu(I) and ROS.
Conclusions:
- The anticancer mechanism of plant polyphenols may involve the mobilization of endogenous copper, particularly chromatin-bound copper.
- This mobilization leads to a prooxidant action, generating ROS that contribute to DNA damage.
- Cancer cells, with typically elevated copper levels, may be particularly susceptible to this mechanism.
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