Interaction of a curcumin analogue dimethoxycurcumin with DNA.
Dimethoxycurcumin (Dimc), a synthetic analogue of curcumin, that has been reported to exhibit better in vivo stability and anti-tumour activity, was investigated for its interaction with DNA, employing spectroscopic methods based on absorption, fluorescence, circular dichroism (CD), ethidium bromide (EtBr) competitive binding assay, 4'-6-diamidino-2-phenylindole (DAPI) displacement assay and fluorescence resonance energy transfer (FRET) assay. The mean binding constant for its interaction with calf thymus DNA (ct-DNA) was estimated to be 4.4±0.8 × 10(4) m(-1) . The studies using CD revealed that Dimc did not cause unwinding of the ct-DNA helix or induce major conformational changes. The EtBr and DAPI assays indicated that Dimc is not an intercalator but a minor groove binder. FRET assay also confirmed that Dimc interacts with DNA strands. Furthermore, viscosity measurements of ct-DNA solutions in the presence of Dimc supported these spectroscopic observations. Addition of Dimc to MCF-7 cells showed nuclear localization as visualized by confocal microscopy. In conclusion, the present studies addressed the mode of interaction of Dimc with biomolecules, which may have implications in developing Dimc as a DNA-targeted drug.
Radiation & Photochemistry Division, Bhabha Atomic Research Centre Mumbai, India. kamit@barc.gov.in
Amit
A
Kunwar
Emmanuel
E
Simon
Umang
U
Singh
Rajnikant K
RK
Chittela
Deepak
D
Sharma
Santosh K
SK
Sandur
Indira K
IK
Priyadarsini
D000818:Animals; D002942:Circular Dichroism; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence
C521105:dimethoxycurcumin; D004247:DNA; D003474:Curcumin