title: Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent.
abstract: The use of small molecules to arrest G-quadruplex structure has become a potential strategy for the development and design of a new class of anticancer therapeutics. We have studied the interaction of myricetin, a plant flavonoid and a putative anticancer agent, with human telomeric G-quadruplex TTAGGG(TTAGGG)3 DNA. Reverse transcription PCR data revealed significant repression in hTERT expression in MCF-7 breast cancer cells upon increasing the concentration of myricetin. Further, we conducted a telomeric repeat amplification protocol assay to confirm the inhibition of telomerase by myricetin. Optical spectroscopic techniques like circular dichroism, UV spectroscopy and fluorescence spectroscopy revealed the formation of a stable myricetin-G-quadruplex complex. The thermodynamic parameters of myricetin-G-quadruplex complex formation, presented through isothermal titration calorimetry studies, indicate the binding process to be thermodynamically favorable. In addition, high resolution NMR spectroscopy in conjunction with molecular dynamics simulation is employed to provide detailed mechanistic insights into the binding in the myricetin-G-quadruplex complex at the atomic level. Our results thus propose a new mode of action of myricetin as an anticancer agent via arresting telomeric G-quadruplex structure.
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata-700054, India. subhro_c@jcbose.ac.in.
authors.forename: Soma
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata-700054, India. subhro_c@jcbose.ac.in.
authors.forename: Jagannath
authors.initials: J
authors.lastname: Jana
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata-700054, India. subhro_c@jcbose.ac.in.
authors.forename: Pallabi
authors.initials: P
authors.lastname: Sengupta
authors.affiliation: Department of Zoology, West Bengal State University, Berunanpukuria, Malikapur, Kolkata-126, India.
authors.forename: Samarjit
authors.initials: S
authors.lastname: Jana
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kankurgachi, Kolkata-700054, India. subhro_c@jcbose.ac.in.
authors.forename: Subhrangsu
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D054856:G-Quadruplexes / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D013057:Spectrum Analysis; D016615:Telomere / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D012333:RNA, Messenger; C040015:myricetin; D004247:DNA