Copper-Redox Cycling by Flavonoid Alpinetin Leads to ROS-Mediated DNA Damage and Apoptosis: A Mechanism for Cancer Chemoprevention.

Abstract

Introduction / Objective: Polyphenols, present in fruits and vegetables and recognized for their anticancer properties, are generally known for their antioxidant abilities; however, they may exhibit prooxidant behavior in the presence of copper ions.

Methods: This study demonstrates that the flavonoid alpinetin inhibits cell growth in the breast cancer cell lines MDA-MB-231 and MCF-7, as evaluated by MTT assay, and induces apoptosislike cell death, as evaluated by Histone/DNA ELISA.

Results: We found the effect to be inhibited by neocuproine, a copper chelator, and by the scavengers of reactive oxygen species (ROS). The inhibitory effect suggests that intracellular copper interacts with alpinetin in cancer cells, leading to DNA damage through the generation of ROS. Additionally, a non-tumorigenic epithelial cell line (MCF-10A) grown in copper-supplemented media exhibits increased sensitivity to growth inhibition by alpinetin, as evidenced by a decrease in cell proliferation. Furthermore, copper supplementation enhances copper transporter CTR1's expression in MCF-10A cells, whereas adding alpinetin to the media reduces this expression.

Discussion: The findings provide additional support for the notion that a crucial anticancer mechanism of plant polyphenols involves the mobilization of intracellular copper and the generation of ROS, ultimately leading to the apoptosis of cancer cells.

Conclusion: These findings demonstrate that alpinetin exerts its anticancer effects through intracellular copper mobilization and ROS generation, ultimately leading to apoptosis in breast cancer cells.