Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Flavanones*/pharmacology ; Rutin*/pharmacology ; DNA Damage*/drug effects ; Antioxidants*/pharmacology ; Breast Neoplasms*/drug therapy ; Breast Neoplasms*/metabolism ; Breast Neoplasms*/pathology ; Molecular Docking Simulation* ; Oxidative Stress*/drug effects; Humans ; Cell Line, Tumor ; Female ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Cell Survival/drug effects

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.
(© 2024. The Author(s).)

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Keywords: 2DD normal human fibroblast cells; Antioxidant activity; Cancer therapy; DNA damage response; Naringin; Quiescent fibroblast cells; Rutin; Selective cytotoxicity

0 (Flavanones)
N7TD9J649B (naringin)
5G06TVY3R7 (Rutin)
0 (Antioxidants)

Date Created: 20240703 Date Completed: 20240703 Latest Revision: 20240706

20250114

PMC11222415

10.1038/s41598-024-63498-7

38961104