title: Mobilization of copper ions in human peripheral lymphocytes by catechins leading to oxidative DNA breakage: A structure activity study.
abstract: Epidemiological studies suggest that dietary consumption of plant polyphenols is related to a lower incidence of various cancers. Among these compounds catechins (present in green tea and other beverages) are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. Thus these compounds can be used as leads to synthesize novel anticancer drugs with greater bioavailability. In view of this in this paper we have examined the chemical basis of cytotoxicity of catechins by studying the structure-activity relationship between catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG). Using single cell alkaline gel electrophoresis (comet assay) we have established the relative efficiency of cellular DNA breakage as EGCG>EGC>EC>C. We also show that cellular DNA breakage is the result of mobilization of copper ions bound to chromatin and the generation of reactive oxygen species. Further the relative DNA binding affinity order was confirmed using molecular docking and thermodynamic studies by studying the interaction of catechins with calf thymus DNA. The results suggest that the synthesis of any novel anti cancer molecule based on the structure of catechins should have as many galloyl moieties as possible resulting in an increased number of hydroxyl groups that may facilitate the binding of the molecule to cellular DNA.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Farhan
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Atif
authors.initials: A
authors.lastname: Zafar
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Sandesh
authors.initials: S
authors.lastname: Chibber
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Husain Yar
authors.initials: HY
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Hussain
authors.initials: H
authors.lastname: Arif
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India. Electronic address: smhadi@vsnl.com.
authors.forename: S M
authors.initials: SM
authors.lastname: Hadi
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D002414:Cations, Monovalent; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects; D020552:Comet Assay; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry* / Q000187:drug effects; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D002414:Cations, Monovalent; D002843:Chromatin; D017382:Reactive Oxygen Species; D003300:Copper; D002392:Catechin; D004247:DNA; C427203:calf thymus DNA; C045651:epigallocatechin gallate; C057580:gallocatechol
keywords: Catechin; Comet assay; Epicatechin; Epigallocatechin; Epigallocatechin-3-gallate; Galloyl moieties; ITC; Molecular docking; Structure activity relationship