NDLI: Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent

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Molecular BioSystems Vol - 12 Issue - 7

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Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent

Content Provider	Royal Society of Chemistry (RSC)
Author	Mondal, Soma Jana, Jagannath Jana, Samarjit Sengupta, Pallabi Chatterjee, Subhrangsu
Copyright Year	2016
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.
Starting Page	2506
Ending Page	2518
Page Count	13
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	12
Issue Number	8
Journal	Molecular BioSystems
DOI	10.1039/c6mb00218h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Spectroscopy MCF-7 G-quadruplex Fluorescence Molecular dynamics Breast cancer Flavonoid Circular dichroism Polymerase chain reaction Ultraviolet\u2013visible spectroscopy DNA Isothermal titration calorimetry Nuclear magnetic resonance Telomerase
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent