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  • Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study.

Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study.

International journal of molecular sciences (2015-11-17)
Hussain Arif, Nida Rehmani, Mohd Farhan, Aamir Ahmad, Sheikh Mumtaz Hadi
ABSTRACT

Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources) induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure-activity relationship of myricetin (MN), fisetin (FN), quercetin (QN), kaempferol (KL) and galangin (GN). Using single cell alkaline gel electrophoresis (comet assay), we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tannic acid, SAJ first grade
Sigma-Aldrich
Quercetin, ≥95% (HPLC), solid
Sigma-Aldrich
Tannic acid
Sigma-Aldrich
Tannic acid, Source: Chinese natural gall nuts
Sigma-Aldrich
Trypan Blue, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Kaempferol, ≥90% (HPLC), powder
Sigma-Aldrich
Neocuproine, ≥98%
Sigma-Aldrich
Tannic acid, ACS reagent
Sigma-Aldrich
Trypan Blue, ≥80% (HPLC), Dye content 60 %
Sigma-Aldrich
Galangin, autophagy inducing flavonoid
Sigma-Aldrich
Kaempferol, ≥97.0% (HPLC)
Sigma-Aldrich
Tannic acid, puriss., powder
Sigma-Aldrich
Myricetin, ≥96.0% (HPLC)
Sigma-Aldrich
Trypan Blue solution, 0.4%, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Myricetin, ≥96.0%, crystalline