title: Troxerutin, a natural flavonoid binds to DNA minor groove and enhances cancer cell killing in response to radiation.
abstract: Troxerutin, a flavonoid best known for its radioprotective and antioxidant properties is of considerable interest of study due to its broad pharmacological activities. The present study on troxerutin highlights its abilities to bind DNA and enhance cancer cell killing in response to radiation. Troxerutin showed strong binding with calf thymus DNA in vitro. Troxerutin-DNA interaction was confirmed by CD spectropolarimetry. The mode of binding of troxerutin to DNA was assessed by competing troxerutin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. DAPI fluorescence was drastically reduced with linear increase in troxerutin concentration suggesting possible binding of troxerutin to DNA minor groove. Further, computational studies of docking of troxerutin molecule on mammalian DNA also indicated possible troxerutin-DNA interaction at minor groove of DNA. Troxerutin was found to mainly localize in the nucleus of prostate cancer cells. It induced cytotoxicity in radioresistant (DU145) and sensitive (PC3) prostate cancer cells. When troxerutin pre-treated DU145 and PC3 cells were exposed to γ-radiation, cytotoxicity as estimated by MTT assay, was found to be further enhanced. In addition, the % subG1 population detected by propidium iodide staining also showed similar response when combined with radiation. A similar trend was observed in terms of ROS generation and DNA damage in DU145 cells when troxerutin and radiation were combined. DNA binding at minor groove by troxerutin may have contributed to strand breaks leading to increased radiation induced cell death.
authors.affiliation: Department of Zoology, Savitribai Phule Pune University (SPPU), Pune, 411007, India; Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.
authors.forename: Niranjan A
authors.initials: NA
authors.lastname: Panat
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.
authors.forename: Beena G
authors.initials: BG
authors.lastname: Singh
authors.affiliation: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.
authors.forename: Dharmendra K
authors.initials: DK
authors.lastname: Maurya
authors.affiliation: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India. Electronic address: sskumar@barc.gov.in.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sandur
authors.affiliation: Department of Zoology, Savitribai Phule Pune University (SPPU), Pune, 411007, India. Electronic address: ssg@unipune.ac.in.
authors.forename: Saroj S
authors.initials: SS
authors.lastname: Ghaskadbi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017382:Reactive Oxygen Species
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D006896:Hydroxyethylrutoside; D017382:Reactive Oxygen Species; C005865:troxerutin; D004247:DNA
keywords: Cancer cell killing; DNA binding; Troxerutin; γ-Radiation